IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
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IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
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Designed to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
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After a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
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Our innovative Book Series format brings you:
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Topic Focused Publications - Each topic showcases high impact subject areas
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Renowned Editorial Expertise - Series Editors, Topic Editors, and a team of international Board Members that permanently support each Book Series
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Fast Publishing - quick turnaround which is unique for book publishing
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The benefit of ISSN and ISBN for increased citation and indexing possibilities
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IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\n
IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
We invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
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Note: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5723",leadTitle:null,fullTitle:"Toxoplasmosis",title:"Toxoplasmosis",subtitle:null,reviewType:"peer-reviewed",abstract:"Toxoplasma gondii was first identified more than 100 years ago in the tissues of birds and mammals. Although toxoplasmosis is important all over the world, its approaches to diagnostic strategies considerably differ among countries. Its wide distribution may be attributed to complex transmission patterns and parasite coevolution with multiple hosts. Although T. gondii infections of immunocompetent people are generally considered asymptomatic, infections in immunocompromised individuals, such as those with AIDS or organ transplant recipients, can result in severe consequences. This book, composed of a series of articles, including effective diagnosis of laboratory in toxoplasma infections, congenital toxoplasmosis, relationship between toxoplasmosis and public health genomics, prevalence, genetic diversity of toxoplasmosis, and microparticle vaccines against Toxoplasma gondii by authors from all over the world, presents a wide open point of view for toxoplasmosis.",isbn:"978-953-51-3270-7",printIsbn:"978-953-51-3269-1",pdfIsbn:"978-953-51-4794-7",doi:"10.5772/65152",price:119,priceEur:129,priceUsd:155,slug:"toxoplasmosis",numberOfPages:186,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"5df59700879dad4465b2792556088faa",bookSignature:"Isın Akyar",publishedDate:"June 14th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5723.jpg",numberOfDownloads:17454,numberOfWosCitations:11,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:16,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:33,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 6th 2016",dateEndSecondStepPublish:"November 9th 2016",dateEndThirdStepPublish:"February 1st 2017",dateEndFourthStepPublish:"March 29th 2017",dateEndFifthStepPublish:"May 31st 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"36323",title:"Dr.",name:"Isin",middleName:null,surname:"Akyar",slug:"isin-akyar",fullName:"Isin Akyar",profilePictureURL:"https://mts.intechopen.com/storage/users/36323/images/123_n.jpg",biography:"Dr. Isin Akyar graduated from School of Medicine, Cukurova University, Adana, in Turkey in 1989. She finished her Medical Microbiology Specialty training in Gazi University, Ankara in Turkey in 1999. She joined the Acibadem Labmed Clinical Laboratories in Istanbul in Turkey as a Specialist of Microbiology in 2004. She became Coordinator of Microbiology in 2007. Since 2004 she had several Quality Control trainings. She works in the first accredited laboratory according to ISO 15189 for clinical laboratories in Turkey. In 2008, she joined the Department of Medical Microbiology at Acibadem University in Istanbul in Turkey. In 2011, she was promoted to serve as an Assistant Professor. Her special interests are laboratory quality control, molecular microbiology, parasitology and proteomics studies. \nCurrently she is both serving as Microbiology Coordinator and Assistant Professor. She has been serving as an Associate Editor for the Journal of Acibadem University Science of Health since 2009.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Acıbadem University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1046",title:"Infectious Diseases",slug:"infectious-diseases"}],chapters:[{id:"55047",title:"Toxoplasma gondii Tissue Cyst: Cyst Wall Incorporation Activity and Matrix Cytoskeleton Proteins Paving the Way to Nutrient Acquisition",doi:"10.5772/intechopen.68202",slug:"toxoplasma-gondii-tissue-cyst-cyst-wall-incorporation-activity-and-matrix-cytoskeleton-proteins-pavi",totalDownloads:1878,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Toxoplasma gondii is an intracellular parasite that causes chronic infection by the development of bradyzoites housed in tissue cysts, preferably in the muscles and central nervous system. The composition and the function of the cyst wall are still not fully understood. Are T. gondii cysts able to incorporate nutrients through its wall? If so, how would these nutrients be traversed to cross the cyst matrix to reach the bradyzoite forms? Herein, we tested the uptake capacity of the Toxoplasma tissue cyst wall by employing some fluid-phase endocytosis tracers as peroxidase (HRP) and bovine serum albumin (BSA). Fluorescence images revealed these molecules on the cyst wall as well as in the cyst matrix. The subcellular localization of the tracer was confirmed by ultrastructural analysis showing numerous labeled vesicles and tubules distributed within the cyst matrix in close association with intracystic bradyzoite membrane, suggesting the cyst wall as a route of nutrient uptake. Furthermore, we confirmed the presence of cytoskeleton proteins, such as tubulin, actin, and myosin, in the tissue cyst matrix that may explain the nutrient input mechanism through the cyst wall. A better understanding of the nutrient acquisition process by the cyst might potentially contribute to the development of new therapeutic targets against chronic toxoplasmosis.",signatures:"Mariana Acquarone, Marialice da F. Ferreira‐da‐Silva, Erick V.\nGuimarães and Helene S. Barbosa",downloadPdfUrl:"/chapter/pdf-download/55047",previewPdfUrl:"/chapter/pdf-preview/55047",authors:[{id:"195727",title:"Dr.",name:"Helene",surname:"Barbosa",slug:"helene-barbosa",fullName:"Helene Barbosa"},{id:"196660",title:"Dr.",name:"Marialice F",surname:"Ferreira-Da-Silva",slug:"marialice-f-ferreira-da-silva",fullName:"Marialice F Ferreira-Da-Silva"},{id:"196661",title:"Dr.",name:"Mariana",surname:"Acquarone",slug:"mariana-acquarone",fullName:"Mariana Acquarone"},{id:"196662",title:"Dr.",name:"Erick V",surname:"Guimarães",slug:"erick-v-guimaraes",fullName:"Erick V Guimarães"}],corrections:null},{id:"54830",title:"Prevalence, Genetic Diversity, Tissue Distribution, and Risk Factors Contributing to T. gondii Burden in Domestic Pigs",doi:"10.5772/intechopen.68203",slug:"prevalence-genetic-diversity-tissue-distribution-and-risk-factors-contributing-to-t-gondii-burden-in",totalDownloads:1406,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Toxoplasma gondii is an obligatory intracellular parasite of mammals, including humans and domestic animals. The infection with this parasite has severe clinical consequences, as it causes abortion or fetal abnormalities, encephalitis in immunocompromised humans, ocular toxoplasmosis with chorioretinitis, and it may contribute to Alzheimer disease. Therefore, an efficient control of T. gondii by prevention of the transmission to humans is strongly recommended. Pork is considered as an important source of toxoplasmosis, due to the frequent consumption of the raw or undercooked porcine meat products, a high susceptibility of pigs to the infection, and because of the numerous risk factors, contributing to the prevalence of toxoplasmosis in the pig population. The cellular and humoral immune responses, such as IgM, IgG, IFN‐gamma, and interleukin‐10 or ‐12 production, associated with the acute and chronic infection in pigs, do not prevent development of the tissue cysts, which persist lifelong within the intermediate host. Therefore, the prevalence of T. gondii in the pig population might be an useful indication of the risk associated with the consumption of the porcine meat.",signatures:"Malgorzata Jennes and Eric Cox",downloadPdfUrl:"/chapter/pdf-download/54830",previewPdfUrl:"/chapter/pdf-preview/54830",authors:[{id:"196671",title:"Dr.",name:"Malgorzata",surname:"Jennes",slug:"malgorzata-jennes",fullName:"Malgorzata Jennes"},{id:"196672",title:"Prof.",name:"Eric",surname:"Cox",slug:"eric-cox",fullName:"Eric Cox"}],corrections:null},{id:"55435",title:"Toxoplasmosis and Public Health Genomics",doi:"10.5772/intechopen.69007",slug:"toxoplasmosis-and-public-health-genomics",totalDownloads:1546,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Toxoplasma gondii infection generally causes flu-like symptoms in healthy individuals; however, immunosuppression of the infected individual causes reactivation of the pathogen to its active form and relapse of the toxoplasmosis. Today it is known that toxoplasmosis triggers psychiatric disorders such as schizophrenia as well as behavioral changes such as suicide attempts. Although dermatological manifestations are very rare, the dermatological lesions are not unique. In addition, previous toxoplasma infection also causes congenital infections because of placental infection and causes birth defects and spontaneous abortion. T. gondii strains are mainly divided into three main clonal lineages, yet higher recombination rate causes unusual population structure and heterogeneous distribution of the pathogen. Both genetic variations, of the pathogen and the patients, are important for virulence property and success of the therapies. The scientist focuses on the genetic variations of the pathogens and individuals to achieve effective treatment and developed tailor-made medicines. Thus, understanding the molecular basis of the disease and the link of molecular mechanism with host immunity is important to fully know the disease and related disorders. In this chapter, we would like to evaluate the current knowledge on genetic, molecular characteristics of toxoplasmosis in view of public health genomics.",signatures:"Oymak Sibel, Hız Meliha Merve, Kılıç Sevilay, Büyük Başak, Halil\nİbrahim Taş and Ülken Tunga Babaoğlu",downloadPdfUrl:"/chapter/pdf-download/55435",previewPdfUrl:"/chapter/pdf-preview/55435",authors:[{id:"195597",title:"Dr.",name:"Ulken Tunga",surname:"Babaoglu",slug:"ulken-tunga-babaoglu",fullName:"Ulken Tunga Babaoglu"},{id:"196042",title:"Dr.",name:"Sevilay",surname:"Oguz Kılıc",slug:"sevilay-oguz-kilic",fullName:"Sevilay Oguz Kılıc"},{id:"196432",title:"Dr.",name:"Meliha",surname:"Hiz",slug:"meliha-hiz",fullName:"Meliha Hiz"},{id:"196521",title:"Dr.",name:"Başak",surname:"Büyük",slug:"basak-buyuk",fullName:"Başak Büyük"},{id:"200562",title:"Dr.",name:"Halil İbrahim",surname:"Taş",slug:"halil-ibrahim-tas",fullName:"Halil İbrahim Taş"},{id:"205943",title:"Associate Prof.",name:"Sibel",surname:"Oymak",slug:"sibel-oymak",fullName:"Sibel Oymak"}],corrections:null},{id:"55132",title:"Congenital Toxoplasmosis: In Vivo Impact of Toxoplasma gondii Infection on Myogenesis and Neurogenesis",doi:"10.5772/intechopen.68619",slug:"congenital-toxoplasmosis-in-vivo-impact-of-toxoplasma-gondii-infection-on-myogenesis-and-neurogenesi",totalDownloads:1828,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Congenital toxoplasmosis (TC) from Toxoplasma gondii positive mother to child transmission results in fetal death, abortion, or infantile neurologic and neurocognitive deficits as well as chorioretinitis. This study aims to analyze the morphological changes in brain and skeletal muscle cells of Swiss mouse embryos during experimental congenital toxoplasmosis. Swiss mice, before mating, were gavage inoculation infected with approximately 25 or 50 cysts of ME‐49 strain T. gondii. Eighteen day postcoitus maternal and embryonic muscle and brain samples were collected and processed for histopathological analysis. The muscle tissue from embryos of infected mothers, in comparison with healthy muscle myofibers, exhibited discontinuous and shorter myofibrils, more interfibrillar space and immature cells with fewer stained and poorly defined striated profiles. These in vivo findings might be related to an adhesion protein decrease, observed in vitro, where myogenesis was completely affected during Toxoplasma infection. The neurogenesis was severely affected with irregularly arranged cells, reduced cell density, and a significant intercellular space increase. The brain tissue presented ischemia, cell death, necrosis, and thrombi, increasing according to the degree of the acute infection, which compromised the neurogenesis, thereby justifying brain size decrease in these embryos.",signatures:"Alessandra F. Gomes and Helene S. Barbosa",downloadPdfUrl:"/chapter/pdf-download/55132",previewPdfUrl:"/chapter/pdf-preview/55132",authors:[{id:"195727",title:"Dr.",name:"Helene",surname:"Barbosa",slug:"helene-barbosa",fullName:"Helene Barbosa"},{id:"196610",title:"Dr.",name:"Alessandra F",surname:"Gomes",slug:"alessandra-f-gomes",fullName:"Alessandra F Gomes"}],corrections:null},{id:"54734",title:"Experimental Models of Ocular Toxoplasmosis",doi:"10.5772/67947",slug:"experimental-models-of-ocular-toxoplasmosis",totalDownloads:1397,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"First described in Ctenodactylus gundi and simultaneously in rabbit, Toxoplasma gondii, an etiological agent of toxoplasmosis, affects different species of vertebrates and invertebrates, presenting different manifestations depending on the host. Ocular toxoplasmosis is one of the mean manifestations of toxoplasmosis in humans, affecting 2% of infected individuals in Europe and North America. Otherwise many aspects of ocular toxoplasmosis still await answer. One of the major factors limiting this process is the difficulty to obtain human samples, doing necessary the use of experimental models. By the way, animal models do not express reality of human disease. The present study defines a compilation of report cases and results that supports the choice of an ideal experimental animal model of ocular toxoplasmosis. Actual literature bears new researches contributing in the choice of a specific experimental animal model. Moreover, the choice must consider behavior, period of life, and maintenance in captivity and ocular toxoplasmosis manifestation. Previous studies contribute for a best-chosen experimental animal model, by the way fragmented information makes difficult to compare mostly animal models picked that do not present efficiency enough. In conclusion, experimental animal models are able to bring relevant information about the course of ocular toxoplasmosis.",signatures:"Aléx Martins Nasaré and Roberto Carlos Tedesco",downloadPdfUrl:"/chapter/pdf-download/54734",previewPdfUrl:"/chapter/pdf-preview/54734",authors:[{id:"195931",title:"M.Sc.",name:"Alex",surname:"Nasare",slug:"alex-nasare",fullName:"Alex Nasare"},{id:"195984",title:"Dr.",name:"Roberto Carlos",surname:"Tedesco",slug:"roberto-carlos-tedesco",fullName:"Roberto Carlos Tedesco"}],corrections:null},{id:"55057",title:"The Laboratory Diagnosis in Toxoplasma Infection",doi:"10.5772/67999",slug:"the-laboratory-diagnosis-in-toxoplasma-infection",totalDownloads:2517,totalCrossrefCites:0,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The diagnosis of toxoplasmosis is of great importance due to the damage caused by this parasite in immunosuppressed people or in pregnant women, the diagnosis of an active toxoplasmosis represents a sign to initiate a pharmacological treatment immediately. The diagnosis of Toxoplasma can be performed with direct methods through intraperitoneal inoculation of serum or cerebrospinal fluid, in susceptible mice evaluating the survival and detection of tachyzoites of biological samples. Indirect methods detecting the IgM and IgG isotypes against Toxoplasma have been the tools mostly used and had leaded to discriminate between an active and acute, from a chronic toxoplasmosis. Molecular methods actually Toxoplasma-DNA identification by molecular biology tests like the polymerase chain reaction (PCR) allow the direct detection of the parasite. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs) have been used to identify three strain linages (type I, II and III). Recently, a high-resolution melting method was described to determine the genotype of the infection by Toxoplasma gondii directly from biological samples.",signatures:"María de la Luz Galván Ramírez, Laura Verónica Sánchez Orozco\nand Cynthia Guadalupe Temores Ramírez",downloadPdfUrl:"/chapter/pdf-download/55057",previewPdfUrl:"/chapter/pdf-preview/55057",authors:[{id:"195753",title:"Ph.D.",name:"María De La Luz",surname:"Galvan-Ramirez",slug:"maria-de-la-luz-galvan-ramirez",fullName:"María De La Luz Galvan-Ramirez"},{id:"205998",title:"Dr.",name:"Laura Veronica",surname:"Sánchez Orozco",slug:"laura-veronica-sanchez-orozco",fullName:"Laura Veronica Sánchez Orozco"},{id:"205999",title:"Dr.",name:"Cynthia",surname:"Temores Ramirez",slug:"cynthia-temores-ramirez",fullName:"Cynthia Temores Ramirez"}],corrections:null},{id:"54607",title:"Effective Diagnostic Marker for Serodiagnosis of Toxoplasma gondii Infection: New Developments and Perspectives",doi:"10.5772/67907",slug:"effective-diagnostic-marker-for-serodiagnosis-of-toxoplasma-gondii-infection-new-developments-and-pe",totalDownloads:1579,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Toxoplasmosis is a prevalent parasitic infection caused by an obligate intracellular parasite Toxoplasma gondii. Various methods have been established in the laboratory diagnosis of toxoplasmosis. Among these methods, serological tests are common and provide satisfactory results. However, producing reliable reagents and standard antigen remains difficult and expensive. Replacing native antigens in all current diagnostic kits with standard and reliable reagents are speculated to achieve more sensitive and specific detection that can significantly improve the assay performance. This review provides updated data on toxoplasmosis serodiagnosis. It focuses on the recent trends of producing reliable and standard antigens that have been used in the serological tests of toxoplasmosis, as well as the future direction in this field.",signatures:"Zeehaida Mohamed and Khalid Hajissa",downloadPdfUrl:"/chapter/pdf-download/54607",previewPdfUrl:"/chapter/pdf-preview/54607",authors:[{id:"196695",title:"Prof.",name:"Zeehaida",surname:"Mohamed",slug:"zeehaida-mohamed",fullName:"Zeehaida Mohamed"},{id:"196715",title:"Dr.",name:"Khalid Ali",surname:"Haj Isa",slug:"khalid-ali-haj-isa",fullName:"Khalid Ali Haj Isa"}],corrections:null},{id:"53861",title:"Effects of Nanoparticles in Cells Infected by Toxoplasma gondii",doi:"10.5772/67156",slug:"effects-of-nanoparticles-in-cells-infected-by-toxoplasma-gondii",totalDownloads:1686,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Core‐shell model drug carriers on two nanoscale size levels have been applied in cell culture studies and focused on Toxoplasmosis therapy. In synthesis, a seed of rhodamin B‐labelled polystyrene latex particles was coated by polybutyl cyanoacrylate under physical inclusion of two different new drugs against Toxoplasmosis. Drug‐loaded and drug‐free core‐shell model drug carriers were added to a cell culture of human macrophages, infected by Toxoplasma gondii, following an infection plan. Drug release from the carriers had been studied before by enzymatic degradation by means of pork liver esterase. Particle size decrease by degradation was investigated in a UV/VIS spectrometer via transmission measurements. Drug release profiles were obtained by HPLC studies. The dynamics in the population of infected human macrophages, T. gondii as well as model drug carrier numbers were registered by an FACS (fluorescence‐activated cell sorter). As main result, the drug‐free references in the two series of core‐shell model drug carriers achieved ca.85% of the observed maximum in Toxoplasmosis therapy efficiency. These data were correlated with an immune stimulant effect on the side of the human macrophages, caused by the cell uptake of colloidal substrate, foreign to the body.",signatures:"Sprakel‐Leyke Silja, Paulke Bernd‐Reiner and Presber Wolfgang",downloadPdfUrl:"/chapter/pdf-download/53861",previewPdfUrl:"/chapter/pdf-preview/53861",authors:[{id:"195790",title:"Dr.",name:"Bernd-Reiner",surname:"Paulke",slug:"bernd-reiner-paulke",fullName:"Bernd-Reiner Paulke"},{id:"196028",title:"Prof.",name:"Wolfgang",surname:"Presber",slug:"wolfgang-presber",fullName:"Wolfgang Presber"},{id:"196029",title:"Dr.",name:"Silja",surname:"Sprakel-Leyke",slug:"silja-sprakel-leyke",fullName:"Silja Sprakel-Leyke"}],corrections:null},{id:"54959",title:"IgY-Technology Applied to Studies of Toxoplasma gondii Infection",doi:"10.5772/67997",slug:"igy-technology-applied-to-studies-of-toxoplasma-gondii-infection",totalDownloads:2202,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this chapter, we describe relevant aspects of immunoglobulin Y (IgY) technology for Toxoplasma gondii applications, including comparison of avian IgY antibody with mammalian IgG antibody, egg yolk IgY production and isolation procedures, important applications for IgY antibody, and state of the art and perspectives for IgY‐technology in T. gondii studies. T. gondii is a worldwide public health problem. IgY‐technology provides an alternative antibody (IgY) to mammalian Immunoglobulin G (IgG) antibody. IgY‐technology involves the chicken immunization, yolk IgY isolation, antibody characterization, and purified IgY application to several kinds of methods. Immunized chicken transfers a specific IgY from blood to egg yolk. Phylogenetic distance between chickens and mammals influences the generation of antibody repertoires recognizing an antigen profile. IgY is not bound to rheumatoid factor or mammalian complement protein and thus avoids the false‐positive results. Yolk IgY isolation is carried out by simple procedures that are accessible for any laboratory and, also, for IgY isolation at large‐scale production. IgY‐technology provides antibodies for proteomic studies, diagnostic assays, and immunotherapy. Although IgY‐technology is promising, there is a reduced number of investigations with IgY and T. gondii. Future perspectives involve the use of IgY‐technology for the screening of new T. gondii antigens for diagnostics, therapy, or vaccine, development of innovative techniques for toxoplasmosis diagnostics and may be an immunotherapy for toxoplasmosis.",signatures:"Alvaro Ferreira Júnior, Jandra P. Santos, Paula B. Bassi, Joely F.F.\nBittar and Eustáquio R. Bittar",downloadPdfUrl:"/chapter/pdf-download/54959",previewPdfUrl:"/chapter/pdf-preview/54959",authors:[{id:"196340",title:"Dr.",name:"Alvaro",surname:"Ferreira Junior",slug:"alvaro-ferreira-junior",fullName:"Alvaro Ferreira Junior"},{id:"196404",title:"Dr.",name:"Joely",surname:"Ferreira Figueiredo Bittar",slug:"joely-ferreira-figueiredo-bittar",fullName:"Joely Ferreira Figueiredo Bittar"},{id:"196405",title:"MSc.",name:"Paula",surname:"Boeira Bassi",slug:"paula-boeira-bassi",fullName:"Paula Boeira Bassi"},{id:"196406",title:"MSc.",name:"Jandra",surname:"Pacheco Dos Santos",slug:"jandra-pacheco-dos-santos",fullName:"Jandra Pacheco Dos Santos"},{id:"196407",title:"Dr.",name:"Eustáquio",surname:"Resende Bittar",slug:"eustaquio-resende-bittar",fullName:"Eustáquio Resende Bittar"}],corrections:null},{id:"54853",title:"Microparticle Vaccines Against Toxoplasma gondii",doi:"10.5772/intechopen.68235",slug:"microparticle-vaccines-against-toxoplasma-gondii",totalDownloads:1416,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Significant information indicates that future investigations on Toxoplasma vaccine development have to include adjuvants for enhancing protective immunity against Toxoplasma gondii. Especially, safe and effective adjuvants capable of fulfilling Th1‐dependent cell‐mediated immunity appear to be more likely to be allowed to use for anti Toxoplasma vaccine development. Recently, biodegradable and biocompatible polymers, such as poly (lactide‐co‐glycolide) (PLG) polymers, have been utilized as safe and efficacious adjuvants to encapsulate antigens for producing long‐term release microparticle‐based vaccines. PLG microencapsulation allows the sustained release of antigens and facilitates antigen uptake via antigen‐presenting cells (APCs) to favorably generate Th1 cell‐mediated immunity, which is required for the prevention of T. gondii infection. In our recent work, recombinant surface antigens (rSAGs), including rSAG1, rSAG2, and rSAG1/2, have been, respectively, encapsulated with the PLG polymer for production of PLG‐encapsulated rSAG1 (PLG‐rSAG1), PLG‐encapsulated rSAG2 (PLG‐rSAG2), or PLG‐encapsulated rSAG1/2 (PLG‐rSAG1/2) microparticles. This chapter describes adjuvant effect of PLG microparticles, controlled release of PLG microparticles, PLG microparticles‐immune system interaction, Toxoplasma SAG‐loaded PLG microparticles, protective immunity by Toxoplasma SAG‐loaded PLG microparticles, and future prospects. 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1. Introduction
Orchids (family Orchidaceae) being iconic are at the front line of extinction, with 17,000–35,000 species distributed globally and are under threat [1, 2, 3]. The family is cosmopolitan in its distribution, but the genera and species are highly endemic [4]. In the Orchidaceae, greater levels of ecological specializations associated with global climate change, have a direct impact on the species diversity and levels of threat, to the extent that many terrestrial orchids in temperate regions have become extinct.
Australia is rich in terrestrial orchid diversity (82%) with approximately 115 genera. The Southwest Australia Floristic region (SWAFR) is among 25 hotspots of biodiversity globally [5]. They can be found in a wide range of habitats across the continent and are usually categorized as epiphytes, lithophytes, and terrestrials, where epiphytes and lithophytes are mostly distributed in the warm and moist regions of tropics (18%) while few species are found in temperate regions of eastern Victoria and Tasmania [5]. They are mostly found in sclerophyll open forests and swampy coastal scrub lands. They grow on the ground especially in open habitats such as grasslands, heathlands and forest floors with low annual rainfall, showing seasonal changes and are mostly distributed in the southern temperate zones of Australia which have a Mediterranean climate. Most of the orchids growing in these temperate regions are deciduous, surviving climate extremes beneath the soil surface by undergoing dormancy [6].
They usually have subterranean fleshy thick tubers or tuberoids that store nutrients during dormancy. Some of the most common terrestrial orchid genera found in Australia are, Caladenia (Spider orchids), Pterostylis (Greenhoods), Diuris (Donkey orchid), Acianthus (Mosquito orchid), Prasophyllum, Thelymitra (Sun orchids), Microtis and Glossodia (Figure 1) [5]. Caladenia’s are (spider orchids) endemic to Australia and represent one of the extraordinary terrestrial orchids with a large number of threatened and rare taxa [6]. In total there are 132 species of spider orchids which are mostly distributed throughout southern Australia.
From the ecological point of view, these orchids could act as ecological indicators of a healthy environment [7]. Due to their complex interactions with pollinators, fungal endophytes, and associated host trees, their conservation involves challenges at species-specific levels. These challenges are mostly linked to their habitat destruction and fragmentation, land use, climate change and unsustainable exploitation of biodiversity [8, 9]. Also, most of the terrestrial orchids of Australia, are continuously encountered by inappropriate fire regimes at different developmental stages of its life cycle, and places 74% of threatened orchid species at risk of extinction [10, 11, 12]. Recently, the impact of nature-based tourism has also been reported as a major threat to the decline of threatened orchid populations in the wild in South Australia [10]. Due to these factors, the survival of various species from this genus is at risk and thus considerable effort is required from scientists and conservation practitioners to overcome these challenges of the twenty-first century. However, with the ability to use current novel technologies in orchid biology greater than ever before, we can help them conserve for future generations.
Australian soils are generally deficient in nutrients, which have mostly leached out of the sandy soils (podzols) over many millions of years [13]. In a fire-prone Australian ecosystem, fungi can have a major influence on surrounding biota and play an essential role in maintaining the healthy ecosystems as effective symbiotic partners, decomposers, nutrient cyclers and are a source of food for various organisms. The top horizon of organic matter is the major source of carbon (C), nitrogen (N) and phosphorus (P). In most coarse-rooted plants like orchids, with a poorly developed root system, mineral nutrition is highly dependent on mycorrhizal uptake of essential elements such as N and P from their surroundings [14]. Orchid mycorrhizal fungi (OMF) present in these nutrient-depleted soils are likely to derive their nutrition from the organic matter (dead roots, exoskeletons, leaves and wood in a litter), which holds various types of complex compounds. These complex molecules are further degraded into simpler forms by the activity of these mycorrhizal fungi and other microorganisms. C is usually available in complex forms such as cellulose, hemicelluloses, pectin and lignin, as well as simple soluble breakdown products from these complex polymers. Also, availability of N is usually in the form of organic peptides, proteins and amino acids and as inorganic ammonium and nitrate ions whereas phosphorus is mostly available as organic compounds such as phytic acid and sparsely available as inorganic ions such a PO43−, HPO42− and H2PO4.
The ability of OMF to assimilate various C, N and P compounds as compared to other ericoid mycorrhizal (ERM) and ectomycorrhizal (ECM) fungi, has been studied previously but information available until now is fragmentary [15, 16, 17, 18]. It is very important to understand the nutritional physiology of endophytes associated with terrestrial orchid species while considering any recovery plans for propagation, management, conservation and restoration of Australian endangered orchid species in wild. Therefore, in this chapter, we have discussed in general about orchid endophytes and their saprophytic ability in digesting complex resources, confined to its litter prone, open and well-drained podzol sites.
2. Orchid fungal endophytes
All orchids share obligate relationships with their endophytes, from early seed germination stages to later development of seedlings and mature plants. Endophytes are commonly found inside the healthy tissues of orchid roots as bacterial and fungal endophytes without causing any symptoms of a disease. In this mutualism, fungus provides water and mineral nutrition to the host plant which in turn provides photosynthetically fixed carbon back to its fungal partner [4], phenomenon which is commonly found in fully autotrophic orchid species [19] as compared to completely mycoheterotrophic (MH) and partially MH orchid(Mixotrophic)species [20, 21, 22].
Physiology of orchid seed germination is one of the interesting phenomena of nature and therefore must enter symbiotic interaction with a species-specific symbiont for appropriate germination. All orchid species are MH in their early stages of seed development, where orchids obtain their nutrition in the form of minerals, salts, water and carbon supply from their fungal symbionts at least in their initial seed germination stages [23]. Once the fungus invades the minute orchid seeds (having low endosperm reserves) it kicks starts the germination process, eventually giving rise to an undifferentiated mass of cells known as protocorms. However, this mutual symbiosis between the host and its fungal partner has not been understood completely, it seems that orchid is having a complete control over-regulating the degree and level of these associations. Germination and vegetative propagation in their natural environment is very slow with a rate of <5% [24]. The distribution of orchids and their diversity is dependent on the availability of their fungal symbionts and thus understanding orchid mycorrhizal symbiosis is a key factor to conserve orchids.
2.1 Orchid symbionts: rhizoctonias and other mycorrhizal fungi
Various orchid species have heterobasidiomycetes as their symbionts [25]. The complex assemblage of fungi associated with orchids consists of Agaricomycetes (=Hymenomycetes) taxa [26]. OMF was traditionally classified as anamorphic form-genus (imperfect stage) Rhizoctonia (=Epulorhiza). These correspond to three distantly related basidiomycetous lineages forming teleomorphic genera, including Ceratobasidiaceae, Tulasnellaceae and Serendipitaceae [27]. Although the OMF is well known for its saprophytic abilities [4] they may be found widely as endophytes in non-orchid roots [28] without forming any symptoms of infection.
Recently, a range of mycorrhizal fungi has been found associated with different orchid species, apart from their long evolutionary history of associations with rhizoctonias [26]. OMF studies on MH and mixotrophic orchid species have shown a huge diversity of ectomycorrhizal fungi [23], including saprotrophic fungi from Mycenaceae and Psathyrellaceae and some ascomycete taxa, which suggests that depending upon their host, same fungi could have a potential to form dual associations in nature. Photosynthetic orchids can also associate with a variety of taxa, including Psathyrellaceae and saprotrophic fungal species [29].
Members of Tulasnellaceae, Serendipitaceae (Sebacinales clade B) and Ceratobasidiaceae are well known for their endophytic [30] and saprophytic abilities [31] with few exceptions from Ceratobasidiaceae where some species are plant-parasitic [27]. Serendipita indica is one of the well-studied, root endophyte models and is indeed found mycorrhizal with orchid roots [32]. Fungi in the Serendipitaceae are involved in a wide range of mycorrhizal associations such as ectomycorrhizas, ericoid mycorrhizas, orchid mycorrhizas and even liverworts (Jungermannioid mycorrhizas) [26, 33, 34, 35]. Phylogenetically the Serendipitaceae (formerly called Order Sebacinales) is grouped into two clades: A and B [36]. Clade A species constitutes jelly fungi, having a saprophytic ability through which they can obtain their nutritional demands from wood and other surrounding litter present in their habitat, while Clade B species are common endophytes of underground plant organs [37]. The fungi from Clade B are usually associated with orchids, for example, Caladenia species in Australia, are also associated with ericoid roots, though without having any proof of functional symbiosis so far [33]. There are studies which have shown presence of basidiomycetous hyphae with septal pores on and in sections of ericoid plants by transmission electron microscopy (TEM) whereas, there is an evidence of DNA sequences from the nuclear ribosomal internal transcribed spacer (ITS) region from ericoid roots that grouped within Serendipita group B and contained identical sequences to those from Serendipita vermifera isolates from Australian green orchids [4]. S. vermifera [30] in group B [38], has a confirmed mycorrhizal relationship with some green orchids, e.g. in Caladenia and Glossodia species and is the most common OMF found associated to these taxa [39, 40, 41, 42].
2.1.1 Fungal identification
Traditional approaches were commonly used to identify these fungal endophytes of orchids by isolating the pelotons from the orchid tissues and maintaining them as pure cultures. Mycelia are mostly present as anamorphs and the orchid endophytes are commonly identified based on their morphological (hyphal walls), anatomical differences (spore formation and nucleus number) and anastomosis behavior [43] by using optical, scanning and electron microscopy. Most form chains of small ovoid-globular monilioid cells. Recently, several molecular approaches are extensively used to delimit the fungal endophytes of orchids (Ceratobasidium, Tulasnella and Rhizoctonia = Serendipita) which are well known for their poor taxonomy [44, 45].
2.1.1.1 Asexual stages
Rhizoctonia is remarkable in some characteristics as they branch out at acute angles when young but at right angles to the main axis at maturity, mainly constricting at the point of branching [46]. Fungi grown from pelotons usually form ovoid monilioid cells without having any clamp connections or conidia in a culture that limits their identification through morphological methods [40]. Rhizoctonia, is traditionally characterized on the basis of anastomosis groupings including the pathogenic strains [47]. Rhizoctonia species are separated on the basis of the ultrastructure of the number of nuclei in each cell and the septa, and on the basis of what can be categorized as uninucleate, binucleate or multinucleate [48]. The commonly isolated Rhizoctonia fungi from terrestrial orchid species are within the anamorphic genera Ceratorhiza, Moniliopsis, Thanatephorus and Epulorhiza.
2.1.1.2 Sexual stages
The commonly isolated Rhizoctonia fungi from terrestrial orchids are species within the teleomorphic genera, Ceratobasidium, Tulasnella and Serendipita. Imperfect stages of Rhizoctonia are commonly found in various chlorophyllous orchids. For most Australian green orchids, in-vitro cultures produce only monilioid cells but Warcup and Talbot obtained teleomorphic stages on Rhizoctonia isolates in culture [40, 41, 49], an achievement not replicated by many researchers despite numerous attempts. Because of this, the systematics of Rhizoctonia-type OMF has been studied using both morphological [43, 46] and molecular approaches [25, 38, 44, 45, 50], which have suggested various anamorphs and teleomorphs for this polyphyletic group.
3. Fungal endophytes of myco-heterotrophic (MH) and autotrophic orchids
The nutrition of orchids is closely tied to the nutrition of their basidiomycetous OMF. The fungal symbionts provide essential nutrients for the establishment of orchid seedlings from obligate MH stage to mixotrophic to fully autotrophic stages of their development. They can obtain their nutrition as saprophytes, by breaking down wood and other litter in their habitats or by tripartite symbiosis, in which the OMF is also ectomycorrhizal on the roots of the surrounding higher plants. Both result in networks of hyphae linking the host plants to various habitats.
In general, achlorophyllous orchids mostly have mycorrhizal associations with homobasidiomycete fungi in the Cantharellales, Thelephorales, Agaricales, Serendipitaceae, Hymenochaetales, and Russulales, which are also pathogenic and ectomycorrhizal on higher plants [51]. In MH orchids, the fungi often form tripartite relationships, being ectomycorrhizal with woody plants and endomycorrhizal with orchids [23, 52, 53] where, transfer of carbon has been shown from the woody plants to the orchid [52, 54]. Fungal symbionts of MH orchids have three lifestyles: ectomycorrhizal (ECM), e.g. Corallorhiza-Russulaceae, parasitic (pathogenic), e.g. Gastrodia—Armillaria species, and saprophytic, e.g. Epipogium—Coprinus and Psathyrella species. Various achlorophyllous orchids such as Gastrodia confusa [55], G. elata [56], Epipogium roseum [57] and Fulophis zollingeri [58], are associated with many species of saprophytic wood- and litter- decaying fungi. Earlier studies have provided morphological and ultrastructural evidence that fungi from the Serendipitaceae formed ectomycorrhiza with Corylus avellana and Carpinus betulus [25] suggesting that common mycorrhizal networks (CMNs) are likely to be found in the plant communities where MH orchids are distributed in the close vicinity of ectomycorrhizal higher plants where they can obtain their nutrition through a tripartite relationship. Molecular studies have also shown the presence of Serendipita species on MH orchids such as Hexalectris spicata and Neottia nidus avis, suggesting that, if Serendipita is ubiquitous in its distribution, it is of interest to elucidate any functional symbiosis with ECM on higher plants.
Chlorophyllous orchids mostly have mycorrhizal associations with fungi in the Rhizoctonia alliance, in the Cantharellales and Sebacinales (Serendipita Group B), with sexual stages in the Ceratobasidiaceae, Serendipitaceae and Tulasnellaceae [4]. Some of the Rhizoctonia species in the Ceratobasidiaceae are also plant pathogens of crops [4]. Fungal endophytes from the Serendipita group are common among photosynthetic orchids, e.g. Caladenia [42, 59] and non-photosynthetic terrestrial orchids, e.g. Neottia [53, 60, 61]. They constitute two major groups: A and B [36]. Group B forms mycorrhizae with green orchids while group A is generally associated with ECM and some non-photosynthetic orchids [26].
4. Fungal specificity
Fungal specificity is common in Australian terrestrial orchids [39, 62]. Taxonomically related groups of Australian terrestrial orchid genera are associated with taxonomically related groups of fungi. Both achlorophyllous and chlorophyllous orchid species can have fungal specificity [57, 63] but is more remarkable among heterotrophic orchid species [64]. By contrast, chlorophyllous photosynthetic mycorrhizal plants are said to be generalists in their associations with mycorrhizal fungi [4], though there is evidence of specificity at the species and strain level in Australian OMF and their host orchids, especially Caladenia [17, 65].
Most common genera of seasonally dormant terrestrial orchids in Australia belong to the Tribe Diurideae; within this, genera in the Sub-tribe Prasophyllinae usually associate with Ceratobasidium, those in the Caladeniinae with Serendipita, and most of those in the Diuridinae, Drakaeinae and Thelymitrinae associate with Tulasnella. Genera in the Acianthinae and the Megastylidinae associate with Serendipita and/or Tulasnella, e.g. Thelymitra. calospora and Lyperanthus nigricans associated with a wide range of endophytes. Also, variations in seed germination rates with fungal isolates of T. calospora were noticed in Diuris species [39]. However, within these general relationships, fungal strain, seed and fungal provenance play an important role; specificity varies from high in C. tentaculata, in which seed and fungal provenance both varied seed germination significantly, to low, in which more than one species of Tulasnella stimulated germination in Thelymitra [39].
OMF effectiveness leads to increased seed germination rate and fitness of orchids [66]. Specificity can be strictly restricted to the early seed germination stages of orchid or involve the compatibility of the fungal symbiont with the orchid throughout later stages [67]. Masuhara and Katsuya [62] has expanded fungal specificity into “potential and ecological specificity” whereas, earlier in-situ seed baiting studies from endangered and common orchids have shown distributions of OMF independent of their host orchids [68], suggesting that the patchiness of many orchids is not due to patchiness of their compatible species.
Previous research has also shown fungal specificity with particular orchid species during germination stages; for example, Neottia nidus-avis needs a specific Serendipita-like fungus to germinate [61]. Fungal specificity and effectiveness vary with individual isolates associated with the host orchid species for example, OMF isolated from Caladenia species were effective in germinating seeds of both Caladenia and Glossodia as compared to Eriochilus cucullatus and Acianthus reniformis [39]. These seed germination tests, under in-vitro conditions, over-estimate the potential of OMF isolates to form effective symbioses with orchid species, and results in a failure of symbiosis during later stages of orchid development thereby parasitizing the host plant [69]. Also, it does not explain the fungal switching that has been recorded during the lifetime of an orchid in the wild [70].
5. Nutritional trends in OMF
Decomposition of organic materials present in the form of dead decaying material such as fallen leaves, litter, hair, exoskeletons and any other kind of waste product from plants or animals is the main source of carbon compounds available.
In forest ecosystems, mineral nutrients in the form of P and N are mostly locked within living organisms or in the organic layer of soil. The distribution of these resources is heterogeneous in terms of space and time [71]. Access to nutrients by the host plant depends on the ability of the mycorrhizal fungi to mineralize the available organic nutrients to intermediate and soluble forms and then mobilize them to the host plant [72]. OMF can grow freely in the environment and have an ability to sustain itself without its host [21]. Mycelium is the predominant vegetative form among the basidiomycetes, comprising interconnected hyphae [71]. Fungal foraging for the uptake of minerals and other resources that are interlocked in the organic layer of the soil largely takes place at hyphal tips. Fungal hyphae have a large surface to volume ratios and secrete enzymes that digest extracellular organic resources, which are further translocated to a sink in the form of simple soluble compounds [73]. From the nutrient-deprived ecosystems of Australia, very limited information is available on the ability of OMF to utilize various C, N and P sources from the complex litter present on the forest floors.
For successful symbiotic interactions, efficient utilization of nutrients by the fungal partners is a prerequisite. In most mycorrhizal associations, photosynthetic products are transferred from an autotrophic host plant to a heterotrophic fungal partner, while the mineral nutrients obtained from the soil move in the opposite direction [74]. By contrast, in mycorrhizae of the photosynthetic orchids, the flow of nutrients is bidirectional, at least in some orchids [19]. In orchids, nutrient uptake into OMF occurs mainly through the acquisition of soluble nutrients from the decay of organic litter present in the top 4–12 cm of topsoil [73]. Information on the types of soluble carbon sources OMF can utilize from the environment and their host plants are very limited.
Few studies have reported inter- and intra- specific variations in utilization of substrates among orchid and ericoid mycorrhizal fungi from the same habitat [16, 18]. Also, Wright et al. [17] provided evidence of genetic and functional diversity among OMF isolates of C. tentaculata that varied in germination rates and utilization of some C and N sources. Unlike many ECM basidiomycetes, OMF has also retained the genes for the breakdown of these complex carbon compounds [31]. Understanding the nutritional roles of OMF may explain the diversity noticed among fungal isolates, from even single orchid plants in rates of symbiotic seed germination in vitro. However, in most cases, only one symbiotically effective fungus was examined from each orchid species from their habitat despite, a large number of fungal variations commonly isolated from even single plants. The symbiotic effectiveness of these isolates might vary with their ability to take up and utilize various carbon sources from their surroundings, an aspect that has not been studied so far.
5.1 Carbon sources: saprophytic ability of orchids and their dependence on mycorrhizal partners
During the early stages of orchid seed development, both achlorophyllous and fully autotrophic orchid species lack their ability to synthesize carbohydrates and the only available source of carbon and nitrogen to these plants is through OMF associated to them. One of the common assumptions so far in the orchid biology is that OMF can obtain its nutrition by digesting the litter components present on the forest floors and there has not been much evidence of their ability to grow on these litter components apart from few studies [15, 16, 17, 18, 75]. There are reports where orchids are found in close vicinity of moss lying on the forest floors but there is no scientific evidence showing the presence of OMF on them or surrounding litter [15]. S. vermifera complex is mostly root biotrophic [37] and is associated with Caladenia species that is believed to be saprotrophic, at least as far as the fungi isolated from the Australian orchids is concerned.
In their natural habitat’s orchids are commonly surrounded by litter such as bark, leaves and wood. During ex-situ measures for orchid conservation, these components have been extensively used as mulch in the pots of orchids to retain proper moisture levels. In Australia, Casuarina branchlets are commonly used as a source of mulch for re-emergence and growth of orchids during ex-situ conservation measures based on an assumption that they help orchid leaves from drying up but there is a possibility that these litter components on their break down may help them in the nutrition of the OMF and hence the orchid growth [75]. Recently, Mehra et al. [15] have validated their use in ex-situ cultivations by showing the amounts of fungal biomass produced on natural and semi-purified substrates from various endangered and common Caladenia species under in-vitro conditions.
5.1.1 Complex carbon sources in a litter
Nutrient-poor soils are inadequate in their microbial decomposition rates and the dead organic matter present on the soil is mostly utilized by decomposer fungi [76]. Litter constituting bark, wood, and leaves have biopolymers such as chitin, pectin, lignin, cellulose, hemicellulose and contain complex cell wall polysaccharides along with chitin of fungal and invertebrate origin. Most of this organic waste is in the form of plant cell wall components which constitutes 90% of plant cell wall components, having three major polysaccharides: cellulose, hemicelluloses and pectin [77]. Of these, cellulose and pectin are key components of organic substrates in vegetation and are an important source of nutrients for ectomycorrhizal fungi [78]. Also, chitin is the main polysaccharide found in fungal cell walls and invertebrate exoskeletons [79] having significant quantities of nitrogen. These complex biopolymers are degraded enzymatically into simpler water-soluble forms of sugar through saprotrophic or mycorrhizal fungi reflecting their saprophytic ability which can be indirectly related to the survival of their host plant. For the survival of the host plant in wild, its nutritional demands for carbon and energy are met by the decomposition of this organic content present in the environment by OMF at the same site. Little information is available on the saprophytic behavior of OMF and more research is required to understand the nutritional physiology of both the partners by having a complete understanding of the role of OMF in decomposing the organic matter present in the ecosystem.
5.1.2 Litter degradation through enzymes
The decomposition of organic matter by saprotrophic basidiomycetes is a complex mechanism and does involve the participation of various enzymes and reactions. Saprophytic fungi stand apart from other organisms in their ability to decompose non-protein sources [73]. Various chlorophyllous and achlorophyllous orchid species are associated with saprophytic fungi from species of Rhizoctonia and Epulorhiza [80]. Utilization of these complex compounds in a litter is associated with the activity or production of extracellular enzymes (endo- or exo-) in basidiomyceteous fungi. These complex sources of carbon are degraded into their simpler forms through the activity of hydrolytic enzymes. Various litter components require a different set of enzymes for decomposition to occur such as cellobiohydrolases, Endo-1,4-β glucanases, and 1,4-β-glucosidases which effectively decompose cellulose to cellobiose. β-glucosidases then convert cellobiose to glucose.
Hemicelluloses are the second most abundant, heterogeneous polysaccharides present in the plant cell walls and comprise branched polymers of 500–3000 C5 or C6 sugars [81]. Lignin and plant cell wall polysaccharides (hemicellulose) interact with cellulose fibers to strengthen plant cell walls. Pectinases are widely produced by plant pathogens and endopolygalacturonase is one of the major enzymes involved in pathogenesis produced by a large number of pathogens such as Rhiizoctonia solani [82], Phytophthora infestans and Verticillium species [83]. Several pathogenic fungi degrade pectin and the release of these enzymes allows them to infect their host plant under favorable conditions but activates the cascade of defense reactions in plant cells [84].
Recent studies on OMF from Australian orchids, in the genera Caladenia, Diuris, Drakaea and Pterostylis, have shown utilization of pectin as a sole carbon source, resulting in the production of fungal biomass ranging from greater than to less than that on xylan [16]. Several extracellular enzymes, such as dehydrogenases and oxidases from the mycelium, are involved in wood-lignin decomposition and have the potential to utilize all major constituents of litter [81]. Microbial decomposition in heathland soils is a slow process [85] and the penetration of the resource is important [86]. Most wood-associated decay reactions occur close to fungal hyphae due to limited amounts of diffused enzymes [81] and lignocellulose-degrading units in the cell walls [87]. Burnett [88] proposed that enzyme secretion may occur in different areas of the apical region and these findings were further supported by experimental evidence in Neurospora crassa, where structural and physiological differences in the hyphal cell wall at the apical region contributed to the variation in secretion and retention of exoenzymes in the wall.
5.1.3 Breakdown of complex sources into soluble compounds and their use
In many ecosystems, most of the nutrients are locked up in organic compounds, soil microflora and microfauna. Organic macromolecules present in the soil are degraded to intermediate forms through the saprophytic ability of decomposers adding up to higher decay rates in the soil [89]. Some of the complex compounds in the form of cellulose, hemicelluloses (xylans and arabinoxylans), starch and pectin are degraded to soluble intermediate forms such as oligosaccharides, disaccharides, cellobiose, xylobiose and maltose which are finally broken down to their soluble breakdown products such as glucose, mannitol, trehalose, arabinose, galactose, mannose, xylose, rhamnose and glucuronic acid.
On penetrating a substrate, fungi decompose it and absorb its nutrients. The available nutrients help the fungus to grow and proliferate until the nutrients are depleted and fungus becomes dormant. In nature, succession starts at this point and other species feed on the remains. Succession in microorganisms is very important in completely digesting complex carbon sources to simple soluble compounds. The C:N ratio plays a vital role in determining microbial growth and the amount of decomposition taking place. Inter-relationships are sometimes antagonistic, with exploitation, antibiosis and competition being very common [89]. An average of 30–40% of C from decomposed substratum is assimilated by the fungi under favorable conditions [89].
OMF, as saprophytes, break down these complex macromolecules and transfer the intermediate and final soluble products to their hosts. The fungal partner increases the efficiency of the host plant in acquiring C, N and P from litter and soil.
So, it is important to understand the ability of OMF to utilize soluble carbon sources. Fungi break down complex molecules into intermediate and then simpler water-soluble forms. These soluble forms are then assimilated and used in metabolic pathways, or liberated as free metabolites, to be used by the OMF or competitive microorganisms, and may be subsequently transferred to the host plants.
5.1.3.1 Use of soluble carbon sources by OMF
Some of the soluble compounds released on the digestion of complex carbon sources are simpler soluble forms of sugars in the form of monosaccharides and disaccharides. OMF vary in their absorption of nutrients from the soil, similar to other mycorrhizal fungi. The ability of OMF to utilize a range of soluble carbon compounds has been studied previously but information available is fragmentary if compared to other mycorrhizal groups such as ERM and ECM fungi. Earlier physiological studies have stated that OMF metabolize sugars through an activity of enzymes such as and maltases and diastase-invertases [90]. There is little information available on the activity of enzymes and transporters involved in OM symbioses, but soluble carbon sources are likely to be transported rapidly to both pelotons and orchid cells which are later used in metabolism. Moreover, few studies have demonstrated the translocation and hydrolysis of the disaccharide sugar trehalose at the interface of the symbionts in MH orchids [91, 92]. Isotopic studies have shown a two-way transfer of carbon between the OMF and the orchid host [91, 93, 94] and it has recently been suggested that C and N containing compounds (derived from glucose and ammonium nitrate) are transferred from both senescent and live pelotons in Spiranthes sinensis–Ceratobasidium sp. AG-1 symbiosis in vitro [95].
To understand the potential of OMF to use soluble carbon sources requires their growth on a range of single carbon sources followed by measurement of their growth as fungal biomass. Research on Australian OMF has generally shown utilization of various soluble carbon sources such as the C5 arabinose, C6 glucose, C12 sucrose and cellobiose, and C(n) cellulose (as CMC), xylan, and pectin, and tannic acid [16, 17, 18]. Biomass on soluble carbon sources can be easily quantified by measuring the dry weight of mycelium and subtracting the biomass of controls from all the treatments, as used by Midgley et al. [16], Wright et al. [17] and Nurfadilah et al. [18] and Mehra et al. [75]. More recent studies have shown trends in utilization patterns of carbon sources across four fungal taxa from the Rhizoctonia alliance (Ceratobasidium, Rhizoctonia, Tulasnella, and Serendipita). OMF from these taxa produced large biomass on xylan, glucose, cellobiose, cellulose, pectin, and to some extent CMC, and the least fungal biomass was reported in all for tannic acid [18]. In studies on OMF from Australian orchids in the genera Caladenia, Diuris, Drakaea and Pterostylis, xylan consistently produced the greatest growth, often exceeding that on glucose [16, 17, 18].
For the establishment of balanced symbiosis between two partners more research using similar methods is required to determine the nutritional preferences displayed by OMF from other Australian terrestrial orchid species. The ability of an OMF to compete for and use soluble carbon compounds from sources external to the orchid may reflect the ability of its host orchid to survive and thrive.
5.2 Nitrogen sources
N present in the soil litter is typically found in the form of inorganic N (nitrates and ammonium) and organic N. Organic N comprises a large fraction of Australian litter but its utilization by OMF has been poorly studied. In the natural environment, amides and amino acids are easily accessible to the OMF, external to the orchid as a result of a litter breakdown and internally in the orchid as a result of plant metabolism.
The utilization of a wide range of organic and inorganic forms of nitrogen by OMF suggests their specificity of enzymes to hydrolyze complex forms of amides and peptides into simpler soluble organic N sources that are directly absorbed by OMF. The uptake and transfer of N by OMF has already been reported previously for northern hemisphere OMF [20, 96, 97] whereas, Cameron et al. [93] provided direct evidence of uptake and transfer of organic N through Ceratobasidium cornigerum (from Goodyera repens) by double-labeling of amino acid glycine. Recently, studies have also shown a transfer of N from the soil and through tripartite relationships by a single OMF of MH orchid, Rhizanthella gardneri [98]. Most recently, the uptake and transport of nitrogen from NH4NO3 was inferred from isotopic enrichment of 15N in the pelotons and uninfected cells of Spiranthes sinensis protocorms using ultra-high spatial resolution secondary ion mass spectrometry (SIMS) [95]. With inorganic N sources, most authors reported greater utilization of NH4+ than NO3− in OMF strains of Tulasnella (one strain, C. flava) and Serendipita (six strains, C. tentaculata) whereas, many of these did not utilize nitrate [17, 18]. With organic sources, most OMF were capable of utilizing C3 alanine, C4 aspartic acid and/or asparagine, C5 glutamic acid and C6 arginine well as compared to C5 proline and C6 histidine which were poorly utilized [17, 18, 99]. Few OMF utilized C2 glycine well and others poorly; the latter included an isolate from C. flava [18]. In addition, only two out of six OMF from Australian Pterostylis species utilized tryptophan [16]. Recently, research work on Australian endangered orchid species (C. fulva) has shown that one of the symbiotically effective isolates, utilized most of the N sources with minimal variations in their biomass in contrary to the ineffective isolate under in-vitro conditions. The reason suggested for this was that it would affect their competition, at both levels in the host plant (internal/external) whereby, an ineffective isolate can successfully outcompete the effective isolate and its host, leading to chlorosis before the death of an earlier surviving orchid seedling [15].
5.3 Phosphorus sources
Most Australian soils are ancient and are phosphorus-deprived, as most of it has been leached out over time [100]. Along with N, it is one of the major limiting factors for plant growth. In soil, it is present in two major forms: inorganic P (Pi) in the form of phosphates where they are present in the form of scarcely available complexes [101] and mineral and organic phosphorus (Po) as phosphate diesters, phosphate monoesters and inositol phosphates [100] where they are low in orthophosphate levels [102]. In natural environments, fungi degrade organic phosphorus compounds present in the dead matter but organic phosphorus locked in humus-rich forest soils is not easily accessible [100, 103]. Inorganic phosphorus has low solubility and is present in three main fractions: soil solution (dissolved phosphates), a labile pool (phosphates adsorbed to surfaces) and a non-labile pool (metal phosphates) [104].
Plants cannot utilize organic phosphates as they only have access to soluble phosphates and can readily absorb them [104]. Mycorrhizal associations can overcome nutrient limitations to plant growth by increasing the availability of phosphorus. Fungi can release phosphorus into the soil solution from organic phosphates with the help of phosphatases, thereby providing access for plants to otherwise insoluble forms of phosphorus [105]. The greater availability of phosphorus to the mycorrhizal plant host is dependent on the ability of its symbiont to absorb and translocate inorganic phosphates to the host roots and to access the forms of phosphorus ‘locked up’ in organic debris [106, 107]. Fungi can store phosphorus in their vacuoles as polyphosphate chains or as condensed phosphate [108].
Terrestrial orchid habitats are nutrient-deprived in Australia and leaf litter is among one of the major phosphorus sources available to OMF [100], through its richness in the cyclic phytic acid (inositol hexaphosphate, IP6, inositol polyphosphate), the main form of phosphorus storage in plants. In orchids it is assumed that mycorrhizal associations benefit the host plant by increasing the uptake of phosphorus. Earlier studies have reported the secretion of acid phosphatases by fungi in pure cultures [43]. The transfer of organic phosphorus in young protocorms of orchids through mycorrhizal fungi was first demonstrated by Smith [109] whereas, the uptake of inorganic phosphorus in mycorrhizal adult seedlings of Goodyera repens has been reported previously. Whilst, the utilization of organic phosphorus was demonstrated by Smith and Read [4] through the hydrolysis of organic compounds with a release of inorganic phosphorus (Pi). So far, there are few studies on the utilization of various forms of phosphorus by OMF in contrast to extensive work done on other mycorrhizae. A recent study by Nurfadilah et al. [18] showed that OMF from four genera of Australian orchids produced greater biomass with inorganic phosphate than DNA and with intermediate levels in case of phytic acid.
6. Ecological implications
Fungal preferences for specific carbon sources from the heterogeneous and unstable distribution of the substrates on forest floors might suggest that different stages of host plant development may have a preference for different organic substrates, for example, the abundance and presence of orchid seedlings (Tipularia discolor) near decaying logs in specified habitats as opposed to their absence near-adult flowering individuals [43] suggests that OMF does have preferences for their carbon sources, which could therefore explains their patchy distribution in the environment. The relative lack of utilization of some soluble components likely to be generated, may offer opportunities and niches for other fungi and microorganisms in general. OMF must compete not only with one another but also with other mycorrhizal and saprophyticic fungi for these resources, and for their breakdown products.
The relative abilities of OMF from Australian endangered and common orchid species (Caladenia spp.) to grow on the breakdown products of litter may have some ecological implications for their orchid hosts in terms of their taxonomy and conservation status [75]. Similarly, Nurfadilah et al. [18] concluded that the OMF from rare and common orchid species has the same utilization profiles of soluble carbon sources, having slow and uncompetitive growth could explain the conservation status of its host orchid. The importance of these nutritional studies can be related to the patchy spatial distribution of OMF and their host orchids [110]. Previous in-vitro studies showed competition between orchid siblings for available resources through their OMF and there is a possibility that this could be true for the orchids growing in the wild [111, 112].
Mehra et al. [75] showed that the OMF from various Caladenia species are differentiated not so much by different profiles of carbon sources utilized but by different rates of growth and final biomass. This suggests that threatened orchids contain OMF with relatively slow-growing and uncompetitive OMF compared with those from common orchids. It would be interesting to test this further by examining more OMF from a greater range of orchids. Also, Ceratobasidium species have rapid rates of growth compared with those of Serendipita and Tulasnella, the other two main OMF of Australian orchids, and it would be interesting to test these in direct competition in microcosms to see the effects on the survival of orchid seedlings of their respective hosts.
7. Conclusion
Orchids depend on their fungal endophytes for their nutritional demands, which is obligatory in its initial stages but may vary in adult green orchids, though they continue to harbor OMF in their underground organs. The forms of C, N, and P available to the OMF can determine their availability to the orchid host and can indirectly affect its conservation status. Thus, obtaining an effective symbiont is critical for an orchid’s survival and is absolutely a high priority in recovery plans for endangered species. In order to develop effective strategies for conservation of orchids, a large number of orchid taxa should be tested for their nutritional modes as a function of their habitat based partly on organic content using labeling techniques and isotopic fractionations. Also, future research should be focused on developing enzymatic profiles for OMF using sterilized natural substrates and insoluble carbon sources, which may augment our understanding of the role of OMF in the decomposition of organic matter in the ecosystem. Uptake of soluble carbon sources in OMF from terrestrial green orchids can be further investigated through radiotracer techniques through labeling and setting up small microcosm experiments. Tracing the translocation of external highly enriched carbon sources over a short period of time will provide evidence on the net transfers of different forms of carbon between the OMF and the orchid.
Acknowledgments
Author acknowledges all the valuable guidance provided by Professor Ann C Lawrie and Dr Fiona Coates from RMIT University, Melbourne, Australia.
\n',keywords:"orchid mycorrhizal fungi (OMF), autotrophic, endangered, conservation, mycoheterotrophic (MH)",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/71812.pdf",chapterXML:"https://mts.intechopen.com/source/xml/71812.xml",downloadPdfUrl:"/chapter/pdf-download/71812",previewPdfUrl:"/chapter/pdf-preview/71812",totalDownloads:581,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:26,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"November 12th 2019",dateReviewed:"March 3rd 2020",datePrePublished:"April 17th 2020",datePublished:"April 7th 2021",dateFinished:"April 17th 2020",readingETA:"0",abstract:"Orchids are unique as they lack a functional rooting system and share an obligate relationship with their fungal symbionts. This relationship supports their host’s nutritional demands from seed germination to its later development. The orchid fungal endophytes explore large areas in the soil as, to which orchid roots have no access, and thus acquire both organic and inorganic nutrients beyond the depletion zone at low carbon cost. Both ‘autotrophic’ (green) and ‘mycoheterotrophic’ species occur in the Orchidaceae, but the term ‘mixotrophic’ is possibly a truer description of the carbon economy of many green orchids. Some of the major ecological threats of an Australian landscape are habitat destruction and fragmentation. There is little known about the nutritional sources and saprophytic ability of orchid mycorrhizal fungi (OMF) and their role in providing nutrition to orchids. However, several integrated approaches have been developed for the conservation, management and restoration of these plants in wild but there is an urgent need to set appropriate conservation priorities to prevent the loss of habitats for these endangered species in terms of their fungal endophytes. This chapter focuses on the protection of these endangered Australian orchid species by understanding the nutritional behavior of their endophytes.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/71812",risUrl:"/chapter/ris/71812",book:{id:"9685",slug:"agroecosystems-very-complex-environmental-systems"},signatures:"Shalika Mehra",authors:[{id:"315183",title:"Dr.",name:"Shalika",middleName:null,surname:"Mehra",fullName:"Shalika Mehra",slug:"shalika-mehra",email:"shalika.mehra@rmit.edu.au",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Orchid fungal endophytes",level:"1"},{id:"sec_2_2",title:"2.1 Orchid symbionts: rhizoctonias and other mycorrhizal fungi",level:"2"},{id:"sec_2_3",title:"2.1.1 Fungal identification",level:"3"},{id:"sec_2_4",title:"2.1.1.1 Asexual stages",level:"4"},{id:"sec_3_4",title:"2.1.1.2 Sexual stages",level:"4"},{id:"sec_7",title:"3. Fungal endophytes of myco-heterotrophic (MH) and autotrophic orchids",level:"1"},{id:"sec_8",title:"4. Fungal specificity",level:"1"},{id:"sec_9",title:"5. Nutritional trends in OMF",level:"1"},{id:"sec_9_2",title:"5.1 Carbon sources: saprophytic ability of orchids and their dependence on mycorrhizal partners",level:"2"},{id:"sec_9_3",title:"5.1.1 Complex carbon sources in a litter",level:"3"},{id:"sec_10_3",title:"5.1.2 Litter degradation through enzymes",level:"3"},{id:"sec_11_3",title:"5.1.3 Breakdown of complex sources into soluble compounds and their use",level:"3"},{id:"sec_11_4",title:"5.1.3.1 Use of soluble carbon sources by OMF",level:"4"},{id:"sec_14_2",title:"5.2 Nitrogen sources",level:"2"},{id:"sec_15_2",title:"5.3 Phosphorus sources",level:"2"},{id:"sec_17",title:"6. Ecological implications",level:"1"},{id:"sec_18",title:"7. Conclusion",level:"1"},{id:"sec_19",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'IUCN. The IUCN Red List of Threatened Species: The IUCN Red List of Threatened Species; 2019. 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Functional and genetic diversity of mycorrhizal fungi from single plants of Caladenia formosa (Orchidaceae). Annals of Botany. 2009;104(4):757-765'},{id:"B70",body:'McCormick MK, Whigham DF, Sloan D, O’Malley K, Hodkinson B. Orchid-fungus fidelity: A marriage meant to last? Ecology. 2006;87(4):903-911'},{id:"B71",body:'Fricker MD, Bebber D, Boddy L. Mycelial networks: Structure and dynamics. British Mycological Society Symposia Series. Elsevier; 2008;28:3-18'},{id:"B72",body:'Finlay R. Action and interaction in the mycorrhizal hyphosphere—A re-evaluation of the role of mycorrhizas in nutrient acquisition and plant ecology. In: BassiriRad H, editor. Nutrient Acquisition by Plants, Ecological Studies. Vol. 181. Berlin Heidelberg: Springer; 2005. pp. 221-276'},{id:"B73",body:'Boddy L, Frankland J, van West P. Ecology of Saprotrophic Basidiomycetes. Elsevier; 2008. 386 p'},{id:"B74",body:'Jakobsen I. Transport of phosphorus and carbon in arbuscular mycorrhizas. 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Chitin degradation by Hymenoscyphus ericae and the influence of H. ericae on the growth of ectomycorrhizal fungi. In: Read DJ, Lewis DH, Fitter AH, Alexander IJ, editors. Mycorrhizas in Ecosystems. Wallingford, UK: CAB International; 1992. pp. 246-251'},{id:"B80",body:'Currah RS, Smreciu EA, Hambleton S. Mycorrhizae and mycorrhizal fungi of boreal species of Platanthera and Coeloglossum (Orchidaceae). Canadian Journal of Botany. 1990;68:1171-1181'},{id:"B81",body:'Baldrian P. Enzymes of saprotrophic basidiomycetes. In: Ecology of Saprotrophic Basidiomycetes. Elsevier; 2008. pp. 19-41'},{id:"B82",body:'Ayers WA, Papaviza GC, Diem AF. Polygalacturonate trans-eliminase and polygalacturonase production by Rhizoctonia solani. Phytopathology. 1966;56(9):1006'},{id:"B83",body:'Ward OP, Moo-Young M, Venkat K. Enzymatic degradation of cell wall and related plant polysaccharides. Critical Reviews in Biotechnology. 1989;8(4):237-274'},{id:"B84",body:'Hahn MG, Darvill AG, Albersheim P. 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Fundamentals of the Fungi. Englewood Cliffs, NJ, USA: Prentice-Hall, Inc.; 1972. p. 482'},{id:"B90",body:'Burgeff H. Die Wurzelpilze der Orchideen, ihre Kultur und ihre Leben in der Pflanze. Jena: Gustav Fischer; 1909'},{id:"B91",body:'Smith SE. Carbohydrate translocation in orchid mycorrhizas. New Phytologist. 1967;66(3):371-378'},{id:"B92",body:'Smith SE, Smith FA. Structure and function of the interfaces in biotrophic symbioses as they relate to nutrient transport. New Phytologist. 1990;114(1):1-38'},{id:"B93",body:'Cameron DD, Leake JR, Read DJ. Mutualistic mycorrhiza in orchids: Evidence from plant-fungus carbon and nitrogen transfers in the green-leaved terrestrial orchid Goodyera repens. New Phytologist. 2006;171(2):405-416'},{id:"B94",body:'Cameron DD, Johnson I, Leake JR, Read DJ. Mycorrhizal acquisition of inorganic phosphorus by the green-leaved terrestrial orchid Goodyera repens. Annals of Botany. 2007;99(5):831-834'},{id:"B95",body:'Kuga Y, Sakamoto N, Yurimoto H. Stable isotope cellular imaging reveals that both live and degenerating fungal pelotons transfer carbon and nitrogen to orchid protocorms. New Phytologist. 2014;202(2):594-605'},{id:"B96",body:'Bidartondo MI, Burghardt B, Gebauer G, Bruns TD, Read DJ. Changing partners in the dark: Isotopic and molecular evidence of ectomycorrhizal liaisons between forest orchids and trees. Proceedings of the Royal Society of London. Series B: Biological Sciences. 2004;271(1550):1799-1806'},{id:"B97",body:'Leake JR. Myco-heterotroph/epiparasitic plant interactions with ectomycorrhizal and arbuscular mycorrhizal fungi. Current Opinion in Plant Biology. 2004;7(4):422-428'},{id:"B98",body:'Bougoure JJ, Brundrett MC, Grierson PF. Carbon and nitrogen supply to the underground orchid Rhizanthella gardneri. New Phytologist. 2010;186(4):947-956'},{id:"B99",body:'Stephen RC, Fung KK. Nitrogen requirements of the fungal endophytes of Arundina chinensis. 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The structure and function of the vegetative mycelium of ectomycorrhizal plants. II. The uptake and distribution of phosphorus by mycelium inter-connecting host plants. New Phytologist. 1986;103(1):157-165'},{id:"B107",body:'Sawyer NA, Chambers SM, Cairney JWG. Utilisation of inorganic and organic phosphorus sources by isolates of Amanita muscaria and Amanita species native to temperate eastern Australia. Australian Journal of Botany. 2003;51(2):151-158'},{id:"B108",body:'Bolan NS. A critical review on the role of mycorrhizal fungi in the uptake of phosphorus by plants. Plant and Soil. 1991;134(2):189-207'},{id:"B109",body:'Smith SE. Physiology and ecology of orchid mycorrhizal fungi with reference to seedling nutrition. New Phytologist. 1966;65:488-499'},{id:"B110",body:'Wardle DA. A comparative assessment of factors which influence microbial biomass carbon and nitrogen levels in soil. Biological Reviews. 1992;67(3):321-358'},{id:"B111",body:'Batty AL, Dixon KW, Brundrett MC, Sivasithamparam K. Orchid conservation and mycorrhizal associations. In: Microrganisms in Plant Conservation and Biodiversity. The Netherlands: Springer; 2002. pp. 195-226'},{id:"B112",body:'Rasmussen H, Johansen B. Density-dependent interactions between seedlings of Dactylorhiza majalis (Orchidaceae) in symbiotic in vitro culture. Physiologia Plantarum. 1989;77(4):473-478'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Shalika Mehra",address:"shalika.mehra@rmit.edu.au",affiliation:'
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York and William Neal Reynolds",authors:[{id:"13418",title:"Prof.",name:"David",middleName:null,surname:"Jordan",fullName:"David Jordan",slug:"david-jordan"}]},{id:"13135",title:"Computational Biology, Protein Engineering, and Biosensor Technology: a Close Cooperation for Herbicides Monitoring",slug:"computational-biology-protein-engineering-and-biosensor-technology-a-close-cooperation-for-herbicide",signatures:"Giuseppina Rea, Fabio Polticelli, Amina Antonacci, Maya Lambreva, Sandro Pastorelli, Viviana Scognamiglio, Veranika Zobnina and Maria Teresa Giardi",authors:[{id:"13746",title:"Dr.",name:"Giuseppina",middleName:null,surname:"Rea",fullName:"Giuseppina Rea",slug:"giuseppina-rea"},{id:"15034",title:"Dr.",name:"Fabio",middleName:null,surname:"Polticelli",fullName:"Fabio Polticelli",slug:"fabio-polticelli"},{id:"15038",title:"Dr.",name:"Amina",middleName:null,surname:"Antonacci",fullName:"Amina Antonacci",slug:"amina-antonacci"},{id:"15039",title:"Dr.",name:"Sandro",middleName:null,surname:"Pastorelli",fullName:"Sandro Pastorelli",slug:"sandro-pastorelli"},{id:"15040",title:"Dr.",name:"Maya",middleName:null,surname:"Lambreva",fullName:"Maya Lambreva",slug:"maya-lambreva"},{id:"15041",title:"Dr.",name:"Maria Teresa",middleName:null,surname:"Giardi",fullName:"Maria Teresa Giardi",slug:"maria-teresa-giardi"},{id:"15178",title:"Dr.",name:"Veranika",middleName:null,surname:"Zobnina",fullName:"Veranika Zobnina",slug:"veranika-zobnina"},{id:"22620",title:"Dr.",name:"Viviana",middleName:null,surname:"Scognamiglio",fullName:"Viviana Scognamiglio",slug:"viviana-scognamiglio"}]},{id:"13136",title:"Statistical Based Real-Time Selective Herbicide Weed Classifier",slug:"statistical-based-real-time-selective-herbicide-weed-classifier",signatures:"Irshad Ahmad and Abdul Muhamin Naeem",authors:[{id:"13787",title:"Prof.",name:"Irshad",middleName:null,surname:"Ahmad",fullName:"Irshad Ahmad",slug:"irshad-ahmad"},{id:"23691",title:"Prof.",name:"Abdul Muhamin",middleName:null,surname:"Naeem",fullName:"Abdul Muhamin Naeem",slug:"abdul-muhamin-naeem"}]},{id:"13137",title:"Variable Rate Herbicide Application Using GPS and Generating a Digital Management Map",slug:"variable-rate-herbicide-application-using-gps-and-generating-a-digital-management-map",signatures:"Majid Rashidi and Davood Mohammadzamani",authors:[{id:"14094",title:"Prof.",name:"Majid",middleName:null,surname:"Rashidi",fullName:"Majid Rashidi",slug:"majid-rashidi"}]},{id:"13138",title:"Soil Electrical Conductivity as One Possible Tool for Predicting of Cirsium Arvense Infestation Occurrence",slug:"soil-electrical-conductivity-as-one-possible-tool-for-predicting-of-cirsium-arvense-infestation-occu",signatures:"Milan Kroulik, Atonin Slejska, Dana Kokoskova and Veronika Venclova",authors:[{id:"13477",title:"Dr.",name:"Milan",middleName:null,surname:"Kroulik",fullName:"Milan Kroulik",slug:"milan-kroulik"},{id:"14742",title:"Prof.",name:"Antonin",middleName:null,surname:"Slejska",fullName:"Antonin Slejska",slug:"antonin-slejska"},{id:"14743",title:"Dr.",name:"Dana",middleName:null,surname:"Kokoskova",fullName:"Dana Kokoskova",slug:"dana-kokoskova"},{id:"14744",title:"Dr.",name:"Veronika",middleName:null,surname:"Venclova",fullName:"Veronika Venclova",slug:"veronika-venclova"}]},{id:"13139",title:"Herbicides in the Soil Environment: Linkage between Bioavailability and Microbial Ecology",slug:"herbicides-in-the-soil-environment-linkage-between-bioavailability-and-microbial-ecology",signatures:"M. 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Andrade",slug:"adalgisa-de-andrade"},{id:"13476",title:"Prof.",name:"Sidney",middleName:null,surname:"Aquino Neto",fullName:"Sidney Aquino Neto",slug:"sidney-aquino-neto"}]},{id:"13150",title:"The Bioassay Technique in the Study of the Herbicide Effects",slug:"the-bioassay-technique-in-the-study-of-the-herbicide-effects",signatures:"Pilar Sandín-España, Iñigo Loureiro, Concepción Escorial, Cristina Chueca and Inés Santín-Montanya",authors:[{id:"13724",title:"Dr.",name:"Maria-Cristina",middleName:null,surname:"Chueca",fullName:"Maria-Cristina Chueca",slug:"maria-cristina-chueca"},{id:"13725",title:"Dr.",name:"Ines",middleName:null,surname:"Santin-Montanya",fullName:"Ines Santin-Montanya",slug:"ines-santin-montanya"},{id:"13726",title:"Dr.",name:"Iñigo",middleName:null,surname:"Loureiro",fullName:"Iñigo Loureiro",slug:"inigo-loureiro"},{id:"13727",title:"Dr.",name:"Maria-Concepcion",middleName:null,surname:"Escorial",fullName:"Maria-Concepcion Escorial",slug:"maria-concepcion-escorial"},{id:"23961",title:"Pilar",name:"Sandin",middleName:null,surname:"España",fullName:"Sandin España",slug:"sandin-espana"}]},{id:"13151",title:"Plasmodesmata: Symplastic Transport of Herbicides Within the Plant",slug:"plasmodesmata-symplastic-transport-of-herbicides-within-the-plant",signatures:"Germani Concenco and Leandro Galon",authors:[{id:"13555",title:"Dr.",name:"Germani",middleName:null,surname:"Concenco",fullName:"Germani Concenco",slug:"germani-concenco"},{id:"15476",title:"Prof.",name:"Leandro",middleName:null,surname:"Galon",fullName:"Leandro Galon",slug:"leandro-galon"}]},{id:"13152",title:"7-Keto-8-Aminopelagonic Acid Synthase as a Potential Herbicide Target",slug:"7-keto-8-aminopelagonic-acid-synthase-as-a-potential-herbicide-target",signatures:"In-Taek Hwang, Dong-Hee Lee and No-Joong Park",authors:[{id:"14070",title:"Dr.",name:"In-Taek",middleName:null,surname:"Hwang",fullName:"In-Taek Hwang",slug:"in-taek-hwang"}]},{id:"13153",title:"Possibilities of Applying Soil Herbicides in Fruit Nurseries – Phytotoxicity and Selectivity",slug:"possibilities-of-applying-soil-herbicides-in-fruit-nurseries-phytotoxicity-and-selectivity",signatures:"Zarya Rankova",authors:[{id:"13412",title:"Dr.",name:"Zarya",middleName:null,surname:"Rankova",fullName:"Zarya Rankova",slug:"zarya-rankova"}]},{id:"13217",title:"Herbicide Sulcotrione",slug:"herbicide-sulcotrione",signatures:"Nanxiang Wu",authors:[{id:"14277",title:"Dr.",name:"Nanxiang",middleName:null,surname:"Wu",fullName:"Nanxiang Wu",slug:"nanxiang-wu"},{id:"14804",title:"Senior Experimentalist",name:"Feng",middleName:null,surname:"Jin",fullName:"Feng Jin",slug:"feng-jin"},{id:"14805",title:"assistant researchers",name:"Yong",middleName:null,surname:"Jin",fullName:"Yong Jin",slug:"yong-jin"}]},{id:"13154",title:"The Hemodynamic Effects of the Formulation of Glyphosate-Surfactant 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Leite, Ricardo Afonso and M. Leonor Cancela",authors:[{id:"14471",title:"Dr.",name:"M. Leonor",middleName:null,surname:"Cancela",fullName:"M. Leonor Cancela",slug:"m.-leonor-cancela"},{id:"14472",title:"MSc.",name:"Ricardo",middleName:null,surname:"B. Leite",fullName:"Ricardo B. 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Larramendy and Sonia Soloneski",coverURL:"https://cdn.intechopen.com/books/images_new/9685.jpg",editedByType:"Edited by",editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"78812",title:"Nanotechnology Application and Intellectual Property Right Prospects of Mammalian Cell Culture",doi:"10.5772/intechopen.99146",slug:"nanotechnology-application-and-intellectual-property-right-prospects-of-mammalian-cell-culture",body:'
1. Introduction
Nanomaterials (NMs) are engineered chemical substances or materials with a particle size of 1–100 nm in diameter. Today NMs are extensively explored and engaged for commercial purposes in different fields, and many sophisticated NMs have shown great promise in biotechnology and biomedicine [1]. NMs display inimitable physicochemical attributes due to their size range in nanometers, high surface area, tunable surface charge, unique composition, various morphologies, and surface composition. Due to their remarkable physicochemical attributes, NMs are significantly different from their bulk materials of a similar symphony, allowing them to perform remarkably well with improved functionality, sensitivity, competence, and selectivity towards developing biomedicines. Various NMs are evaluated to get desired biomedical efficacy for nanomedicine-related applications, including different metal nanoparticles, liposomes, quantum dots, polymeric micelles, dendrimers, and carbon-based nanoparticles. Two critical mechanisms for delivering drug-loaded NMs to the diseased sites are passive targeting and active targeting. A passive targeting mechanism happens via enhanced permeability and retention (EPR) [2]. Inactive targeting mechanism relies on surface functionalized NMs with various biomarkers that bind with receptors over-expressed at the pathological tissue [3].
The importance of cell culture advances in the medical sector has long been recognized. Mammalian cell culture (MCC) entails first isolating cells from a specific organ tissue and then creating a culture in a suitable artificial setting. Disaggregation using different methods may be used to obtain preliminary separation of cells from the identified organ tissues. The isolated primary cells are typically obtained from an in vivo setting, although some cells come as established cell lines. MCCs are widely used in the biomedical field to investigate numerous applications [4]. Since cell culture-based studies provide highly stable and repeatable results, researchers consider this technique as an essential model system in cellular and molecular biology. MCC needs an ideal environment for development, which can be divided into nutritional and physicochemical requirements.
Nutritional necessities comprise an adherent substrate or growing medium that offers conditions like essential amino acids, sugars, vitamins, minerals, growth factors, hormones, and gases (O2, CO2). All these features regulate physicochemical factors such as pH, osmotic pressure, and temperature. Many cell lines need solid or semi-solid support in the form of a substrate, while others can be grown in a suspension culture medium. These technologies have evolved as a means of assessing the efficacy and side effects of novel active pharmaceutical ingredients (APIs), immunotherapeutic, and biopharmaceuticals [5]. Animal, plant, and bacterial cells are regularly cultured in fixed culture medium under precise laboratory circumstances; among this, animal-based cell cultures are more complex than others due to their genetic complexity. Directed differentiation of adult stem cells and pluripotent stem cell culture is another challenging aspect. Recent advances in stem cell culture technology have provided significant input for the successful culture of tissue-mimicking 3D organoids [4, 6].
In recent years, nanotechnology (NT) and associated disciplines have gained rapid escalation in biomedical implementations such as diagnosis, testing, tracking, drug delivery, nanomedicine, medical implants, and electronics due to their camaraderie with biological entities. Biomedicine embraces the design and synthesis of NMs, along with other nanoparticles (NPs) and nano-devices [7]. Once properly formulated, NMs show their natural aptitude to traverse with the blood flow via various routes based on their attributes and eventually get access to all the organs. Due to their intrinsic biocompatible interactions, the NPs exhibit unique physicochemical attributes associated with lesser immunogenicity and non-toxicity. There are numerous advantages of using NMs for various biological applications: i) it increases the concentration of drug in the pathological tissues and control the slow release of the drug; ii) it solves issues connected to the low solubility and bioavailability of the drug; and iii) enhanced biodegradability and biocompatibility iv) drugs/genes/imaging agents can be easily loaded due to their tunable surface functionalities [1, 7, 8]. Imaging agents could endow in vivo drug tracking ability to determine drug delivery efficacy during treatment. In recent years, various nanoparticles such as liposomes, polymers, metal nanoparticles, inorganic nanoparticles have been developed for selectively targeting tumor cells and other pathological tissues without causing any destruction to healthy cells or organs. In this chapter, the application of nanotechnology and Intellectual property rights (IPR) prospects of mammalian cell culture will be discussed in the subsequent sections.
2. Compatibility of nanomaterials towards biological interactions
NMs attract considerable interest due to their unique, tunable, versatile physicochemical properties, easy preparation methods, biocompatibility, and surface functionalization [1]. Nonetheless, the compatibility of the nanoparticles with biological entities constitutes the most fundamental phenomenon and highlights the importance of basic research [9]. Most bio-applications, including drug delivery, bioimaging, and treatment, start from the attachment of nanoparticles onto the target cells. The biocompatibility of nanoparticles depends on the physical and chemical attributes like diameter, shape, composition, concentration, functionalized moieties, and surface potential (Figure 1) [10]. Among the various NMs, Quantum dots have risen as an innovative bio-imaging tool due to their unique tunable physicochemical attributes. Existing research has guided the development of versatile quantum dots that are highly fluorescent and stable under diverse biological circumstances. Moreover, quantum dots with enclosed amphipathic polymers have been developed and surface-functionalized with receptor targeting ligands for bio-imaging and drug-delivery in animal models. Fascinatingly, these materials were found to be compatible with the cells. However, their complete chronic in vivo genotoxicity, blood, and organ compatibility need to be assessed [1, 7, 11].
Figure 1.
Precision of targeted drug delivery using nanocarriers and bio-compatibility. Nanoparticle based drug delivery platform depends on surface functionality, size and shape and surface charge and composition.
Polymeric nanoparticles have drawn considerable attention in drug and gene delivery, tissue engineering, and many biomedical applications due to their non-toxic nature and high compatibility to biological systems. They are colloidal in nature and composed of natural or synthetic, or semi-synthetic polymers. In this perspective, biodegradable nanoparticles of the highly compatible triblock copolymer are used for non-viral gene transfections [3].
Liposomes are another popular nanomaterial drug delivery system that is best documented and adapted owing to their bio-congenial physicochemical properties [12]. Liposomes consist of unilamellar/ multilamellar lipid bilayers having an aqueous core inside. The nanoscale carrier system offers substantial advantages such as biodegradability, biocompatibility, ease of synthesis, less toxicity, sustained drug release, and the ability to incorporate hydrophilic and hydrophobic drugs. Liposomal-surface modification is a crucial strategy for targeted therapy and especially for cancer treatment [13]. Seventeen liposomal formulations are clinically approved for cancer, inflammation, infectious diseases, antibiotic drugs, and anesthetics, while several liposomal formulations are under various phases of clinical trials [12, 13].
Despite several encouraging biomedical implementations of nanoparticles, the biocompatible assessments including, complete acute and chronic toxicological evaluation of NMs, are inadequately comprehended. Additionally, the toxicity of the nanoparticle design aims to find out favorable physicochemical attributes of different materials. Hence, the active bio-molecule with biological entities must be highly allied to the nanoparticles approaching direct contact with biological objects rather than its transient initial distribution. Much to our intrigue, various nanoparticles - liposomes, lipoplexes, polymeric nanoparticles, polyplexes, metal nanoparticles, metal oxides, dendrimers, and quantum dots are wisely engineered for their medical application like diagnosis, drug and gene delivery, tissue engineering, and biosensing [8, 13, 14]. Moreover, it is unavoidable to thoroughly assess and investigate compatibility/unwanted toxicity with nanoparticles to bring clinical success. The subsequent section will relate to how the physicochemical properties of engineered nanoparticles can be persuaded towards accomplishing the desired biological aspiration lacking any toxicological impact.
2.1 Tunable physicochemical attributes of nanomaterials compatible with biomedical applications
Nanoparticles exhibit outstanding physicochemical attributes which can be manipulated to harness the best possible benefits out of them - their tunable diameter, high surface area, various morphologies, different concentrations and compositions, surface functionalization, etc. [15] (Figure 1). Interactions of NMs to the cell surface, their internalization, and subcellular localization, communication with the cells eventually contribute to therapeutic or adverse effects. Understanding the physicochemical attributes of NMs and their interactions with biological entities can help design superior NMs for further applications. We are jotting down the relevant physicochemical attributes of nanoparticles, which may modulate their function in therapeutic or toxicity aspects; thus, they need to be engineered wisely [16].
2.1.1 Nanomaterials size
For engineered nanoparticles, the primary crucial feature is their dimensions/size, which partially governs other physicochemical characteristics. The reduced diameter of the nanoparticles, provide possibilities for high cellular localization making them interact with cellular tissues, especially pathological tissue to a greater extent to attain specific biological outcome for the remedial purpose. Size-dependent bio-distribution studies were performed using three different sizes containing (20, 50, and 200 nm) drug conjugated silica nanoparticles. It revealed that nanoparticles having 50 nm diameter had the highest tumor localization, enhanced cancer tissue retention, and slower clearance [16]. Moreover, nano-sized particles preside over their pharmacokinetics, are predictable to traverse biological barriers, which is not possible for bulk particles. Besides, ~50 nm diameter particles showed higher efficacy because of active engagement to the biological tissues, modulating pathways, and cellular activities [17].
2.1.2 Nanomaterials surface charge
The surface charge is a unique character of NMs to manage its therapeutic and toxicological effects and plays a significant role in electrostatic interactions of NMs and living entities (Figure 1) [10]. Besides, the cellular localization pathways and tissue interactions are regulated by the surface charge of the nanoparticles, thus playing a significant role in the compatibility and cellular toxicity. Several reports suggest that nanoparticles with a positive charge highly interact with the negatively charged cell membranes and provoke genotoxicity [18]. Positively charged cationic liposomal drug and gene delivery systems have been extensively studied for the last decade. It was recently shown that cationic lipoplexes are not showing any genotoxicological aberrations in the Swiss albino mice. Typically, cell membranes are anionic in nature; thus, negatively charged NMs have very slow cellular internalization compared to neutral and positive nanoparticles [14]. Surface potentials of metal particles in regulating different tumorous and non-tumorous tissue types are also established. Several studies have suggested the role of the surface potential of different nanoparticles and their interactions with the biological entities and how surface charge modulates their biological functions, which shed light to design and engineer nanoparticles for a selective cellular target for various diseases with minimal toxicity [16, 18].
2.1.3 Surface functionalization
Nanoparticles play a vital role in promoting intracellular delivery of encapsulated therapeutic agents and increase their retention in pathological tissues compared to healthy tissues [1]. Surface functionalization with suitable receptor-targeted ligands using different methods results in the formation of targeted nanoparticles with improved therapeutic response and minimized off-target side effects by prolonging their circulation time in blood, increasing target specificity, cellular uptake, and drug accumulation in the tumors (escaping lysosomal degradation and enhancing stimuli-responsive drug release) (Figure 1) [17, 19]. Depending on their application, nanoparticles are functionalized with different targeting ligands either by directly conjugating ligands to PEGylated nanoparticles through post-insertion technique or by covalent grafting on the surface of the nanoparticles. In this context, surface functionalization of nanoparticles with antibodies, peptides, folic acid, aptamers has been extensively studied. This prompts scientists to design and engineer nanoparticles for selective targeting and high retention in the tumor tissue rendering minimal toxicity to the vital organs [19, 20].
3. Mechanism of targeted drug delivery using nano-carrier
Nanoparticles play a vital role in promoting intracellular delivery of enclosed therapeutic agents and increase their retention in the different pathological tissues compared to other therapies [21]. Like normal tissues, tumors need nourishments by means of food and oxygen and a capacity to remove metabolic excretes and carbon dioxide. Diverse patterns of tumor-associated neovascularization, obtained by angiogenesis, cope with these demands. Primary conservative treatment modalities involved in cancer treatment are surgery, radiotherapy, and chemotherapy, while additional therapies such as immune therapy, targeted therapy, and hormone therapy are chosen depending on the type of tumor [22]. On the other hand, the failure of chemotherapeutic drugs to specifically target cancer tissue hinders many treatment modalities. It is habitually faster and economically cheaper to design an existing drug to encapsulate in a delivery system a more effective way to superior targeting of tissues than to invent a completely new one. The drug delivery mechanism can be classified into passive and active, respectively.
3.1 Nanoparticle drug delivery by passive targeting
Passive targeted drug delivery mainly depends on the physicochemical attributes of the NMs, such as shape, diameter, surface potentials, and pathophysiological conditions of the disease microenvironment. Intravenously injected drug encapsulated NMs tend to disperse throughout the body evenly [23]. However, unlike normal tissues, tumor cells tend to take up particles of a definite diameter to a greater extent than healthy cells due to the arrangement of capillary endothelial cells, accumulating extravasated molecules in the interstitial spaces poor lymphatic drainage increases the permeation and accumulation of drug-mediated NMs. This type of NMs accumulation in the tumor region is known as the EPR effect [1, 2]. The EPR effect is influenced by physicochemical attributes of NM including particle diameter, shape, and surface potentials greatly influence the circulation time, penetration speed, tumor localization, and intracellular internalization.
Particle diameter plays a critical role in achieving effective drug delivery as it enhances permeation and circulation time and reduces renal clearance. For example, phagocyte cells facilitate larger particle uptake, while non-phagocytic cells favor the uptake of smaller particles. PEGylated NPs reduced plasma protein adsorption on their surface and reduced hepatic filtration when their size is smaller than 100 nm [24]. Particle diameter with 20–200 nm effectively enhances the permeation in both hyper-permeable and poorly permeable tumors, and particles with less than 6 nm avoid renal clearance. The NPs surface potentials could play a vital role in circulation and cellular localization [24, 25]. NPs with positive surface potentials such as cationic liposomes induce non-specific interactions with blood components and aggregation of liposomes results in a reduction of EPR effect and increased renal clearance. However, positively charged NPs are more readily taken up by cancer cells. Whereas anionic and neutral surface potential-bearing NPs circulate longer in the blood circulation [1, 2, 24].
Besides, Polyethylene glycol (PEG) polymer is used as a stabilizer (stealth liposomes) that increases the circulation time in blood up to 24–48 hours and improves in vivo stability [26]. PEG-coated liposomes induce the ‘steric stabilization effect’ by creating hydrophilicity on the surface of liposomes that shield surface charge and increases the repulsive forces between liposomes and blood components. Thus, it prevents aggregation of liposomes and opsonization by the reticuloendothelial system, macrophages, mononuclear phagocytic cells and prolongs their systemic circulation. On the other hand, PEG-coated liposomes induce PEG-specific IgM antibodies, enhancing hepatic uptake and rapid clearance of liposomes from systemic circulation on subsequent administration. PEG corona produces steric hindrance with tumor cells that prevent effective internalization, which could be minimized by using short PEG chains with molecular weight less than 1000 Da or by designing PEG with enzyme-cleavable bound or tumor-targeting ligands [20, 26]. To investigate the influence of shape on the cellular localization of NPs, Li et al. conducted large-scale molecular simulations to evaluate different NP geometries with identical surface area, ligand-receptor interaction strength, and PEG grafting density. They observed that spheres exhibited the fastest internalization rate, followed by cubes, while rods and disks were the slowest. Many liposomal formulations have received clinical approval, like Doxil, Abraxane, etc. However, nanoparticles grafted with PEG prolong the systemic circulation of the particles and induces the EPR effect in tumor cells, but lack of target specificity often results in reduced therapeutic efficacy [27]. Because of that, more than 95% of passively targeted formulations fail to go bench to bedside.
3.2 Nanoparticle-based drug delivery by active targeting
An ideal nanoparticle delivery system should be proficient at reaching, recognizing, and delivering its payload to determined morbid tissues and avoid drug-induced toxicity to healthy tissues [7]. Therefore, functionalizing specific targeting moieties on the surface of nanoparticles is the most usual plan. Nanoparticles are functionalized on their outer surface by targeting moieties such as small molecule ligands, monoclonal antibodies, aptamers, cell-penetrating peptides, and proteins that are internalized into morbid cells by interacting with cell surface receptors like folate receptors, transferrin receptors, tyrosine kinases like EGFR, and so on [28] (Figure 1). Cell surface receptors that are significantly overexpressed in diseased cells, compared to normal healthy cells, provide a potential target for the design and development of actively targeted drug delivery and help to reduce off-target effects [7, 17]. These ligand moieties can interact with target-specific diseased cells and protect nanoparticles from enzymatic demolition.
Targeted drug delivery significantly minimizes the toxicity and induces patient compliance with less frequent dosing. Active targeting depends on ligands bound to the NP surface to improve their uptake selectivity and protect NPS from enzymatic destruction. The main principle of active targeting involves functionalizing an NP with a ligand that binds to a molecule overexpressed on cells. Ligands with a high binding affinity to a specific cell type exhibit higher delivery efficiency. One important thing to consider is that healthy cells still express the same molecule, and as healthy cells greatly outnumber, the chances of NPs missing their target will also increase. An intelligent selection and functionalization with multiple ligands can effectively mitigate the problem. Apart from this, active targeting mainly determined the kind of nanoparticle carrier, ligand targeting specific receptors, functional agents used for linking a ligand to the nanoparticles, hydrophilic polymers, and encapsulated active ingredients [28, 29].
Targeting tumor cell surface receptors is a common approach in active targeting. Nanoparticles were linked with targeted ligands for targeting specific cell receptors and thus upregulated the intracellular localization and therapeutic efficiency. Liposomes are conjugated with antibodies, a Y-shaped glycoprotein, or its fragments often termed as immunoliposomes, increasing the specificity of liposomes by targeting antigen-presenting cancer cells, which undergo endocytosis and destroy cancer cells followed by immune system clearance [28]. Folate receptors are membrane proteins overexpressed by various tumor cells. Folic acid is a ligand for targeting folate receptors, which pose high affinity, stability, and conjugation capacity [30]. It is conjugated with nanoparticles and a PEG spacer that inhibits steric hindrance between the cells and liposomes, which helps to increase cellular uptake and drug delivery of folate-targeted anticancer drugs. Targeting folate receptors with folic acid ligands helps deliver therapeutic and imaging agents effectively to the requisite site. Endothelial growth factor receptors (EGFR) overexpressed in solid tumors like non-small cell lung cancer, colorectal, squamous cell carcinoma of the ovary, kidney, head, neck, pancreas, prostate, and breast cancers can help in designing EGFR targeted drug delivery system. Antibody fragments used for targeting EGFR are functionalized on nanoparticle surfaces in order to acquire high targeting specificity [31]. Fibroblast growth factor receptors are overexpressed in cancers like lung, prostate, bladder, etc. Several groups have reported remarkable interaction of FGFs conjugated liposome with FGFR and discussed in detail [32, 33]. Overexpression of CD44 is observed in cancers like leukemia, ovarian, colon, gastric, pancreatic, and epithelial cancers. Hyaluronic acid acts as a ligand for CD44 and is used to deliver gemcitabine and DOX encapsulated within the liposomes [34].
Targeting the tumor microenvironment is another approach in active targeting, and one aspect is targeting the tumor vasculature instead of the tumor. This approach helps in the targeted destruction of neo-angiogenic blood vessels essential for tumor growth and metastasis [29, 35]. Vascular endothelial growth factor receptors (VEGFR) play a significant role in tumor angiogenesis and vascular permeability and regulate other aspects of tumorigenesis. Bevacizumab, a monoclonal antibody approved by USFDA, is used as an anti-human VEGF for targeting VEGFRs and FGFRs tyrosine receptors for active targeting [29]. Vascular cell adhesion molecules (VCAM-1) are cell adhesion molecules (CAMs) present on the endothelial cells responsible for inflammation. VCAM-1 is overexpressed in cancers like non-small cell lung cancer and tumor vasculature. Anti-VCAM and Fab-conjugated liposomes have high cellular uptake into Human Umbilical Vein and Endothelial Cells (HUVEC) compared to conventional liposomes [36].
Matrix metalloproteases (MMPs) are calcium-dependent endopeptidases involved in remodeling extracellular matrix, tumor invasiveness, and metastasis by modulating the formation of new blood vessels [37]. Conjugating MMP-2 cleavable peptides to liposomes loaded with cell-penetrating peptides increase the tumor selectivity. αβ-integrins are the heterodimeric transmembrane glycoproteins that facilitate the adhesion of endothelial cells with adjacent tissue and blood vessels. A tripeptide Arg-Gly-Asp (RGD) exhibited high specificity for αvβ3 integrin helps in developing integrin targeted liposomes, which inhibits adhesion and angiogenesis in the tumor microenvironment (TME) [38]. Active targeting amends the intuitive patterns of a nanocarrier, directing to the specificity of the pathological tissue. In contrast, passive targeting delivery depends on the natural distribution of the therapeutic motifs and the EPR effect. Both the targeting mechanisms depend on blood circulation and the location of initial drug delivery. However, rare commercial advances are made using actively targeted NPs [39].
4. Nanomaterial and their application from biological analysis
4.1 Nanomaterial-driven faster and more accurate cell analysis
Early detection and diagnosis can play a pivotal role in the battle against many diseases. Scientists harness the unique attributes of nanomaterials to generate novel molecular contrast agents for in vivo imaging, sensing, measuring response to therapy, and liquid biopsy to study disease initiation, progression, and therapeutic response. Nanotechnology has a spacious range of accurate cell analyses. As described above, nanotechnology facilitates the development of desired formulations for individual cell analysis and their specific treatment applications, developing only one of its kind of applications for cell sensing/sensors, imaging, delivery, and diagnosis [39]. Since the importance of accurate cell analysis for nanoparticles is the latest approach, there is a big void for more discoveries and optimizations in various bio-applications.
4.2 Nanomaterial and in vivo imaging
The main lacunae in cancer treatment are a late diagnosis. The resolution of current imaging methods is low and can detect cancers at the late/ advanced stage or metastasized. A tissue biopsy can only help physicians to ascertain the tumor type and characteristics. Detection becomes even more challenging when metastatic modules and micrometastasis need to be identified. In vivo imaging enables us to non or minimally-invasively delve deep into the patient’s tissue and is becoming increasingly popular for basic research and clinical applications. In vivo, molecular imaging focuses on obtaining spatiotemporal information about molecules of medical interest or biomarkers within a living body in real-time. Molecular in vivo imaging relies on contrast agents or medium that increases the contrast of physiological structure and enhances the sensitivity of detection. Different contrast agents are used for different in vivo imaging techniques including, radiocontrast, magnetic resonance imaging (MRI) contrast, ultrasound contrast, and optical contrast agents [40]. Precision diagnostics is dependent on high-resolution and high-contrast images. Nanomaterials are critical players in the generation of advanced contrast agents or media. Imageable nanoparticles can be classified based on their applications in nuclear, magnetic, optical, and acoustic imaging modalities. Moreover, NP-based contrast agents may be designed to integrate multiple detection modules and target specific cells. The advantages of nanoparticle-based contrast agents include enhanced specificity, increased photo and chemical stability, longer circulation time, engineered clearance pathways, and multimodal applications. The main in vivo imaging modalities include MRI, computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT), ultrasonography (US), near-infrared fluorescence (NIRF), and two-photon intravital microscopy [41, 42, 43].
4.3 Nanoparticles as bio-sensors
By virtue of their unique properties, NPs make them ideal for their use for nano bio-sensing applications with enhanced sensitivity. Nanoparticles are widely used for detecting cells and pathogens, separating pathogens, recognize different biological substances, and detecting molecular and cellular functions [41, 42]. Accurate and professional separation of desired cells from the composite of various cell mixtures is essential for numerous biological applications. Nanoparticles have been investigated as a promising and very sensitive tool for the specific identification of cells. Identification and incarceration of metastatic cancer cells in the circulation can help understand and a strong analytical biomarker for various metastatic cancers, which can change the patient’s prognosis. Nanoparticle-based methods are more frequently used for the identification and capture of metastatic circulating cancer cells. In this technique, magnetic nanoparticles were used to specifically track and separate the cells by using a ligand-receptor-based mechanism [42]. These techniques can also be used for the white blood cells with an anti-CD45-APC as a nanoparticle targeting ligand [44].
Additionally, various nanoparticle-based technologies have been investigated as a sensor for the identification and selection of various pathogens. The most frequently used method for finding bacteria is magnetic biosensors that involve immunological mechanisms using magnetic nanoparticles functionalized with antibodies against surface antigens. Many researchers have been utilizing small molecule tethered nanoparticles to analyze the bacteria successfully. Magnetic glyco-nanoparticles mediated particles could detect bacteria within 5 minutes, including subtraction from the sample by the bacterial interaction with carbohydrates on mammalian cell surfaces [41].
4.4 Nanoparticles as imaging agents
Nanoparticles have been investigated as imaging agents due to their exceptional physicochemical attributes for various biomedical applications such as cancers and cardiovascular diseases. Fluorescent labels can be easily conjugated to the surfaces of the nanoparticles by various chemical methods to design a wide range of imaging agents for dynamic in vitro and in vivo cellular imaging [45, 46]. Due to their passive and active targeting nature, nanoparticles can easily identify their specific biomarkers and accumulate at high concentrations in the targeted tissue. The high capability for nanoparticle modification and retention properties in the specific tissue region empowers their utilization as imaging amplifiers. Quantum dots are the most promising fluorescent labels for cellular imaging among all nanoparticles due to their inherent near infra region light emitting nature, reducing autofluorescence [47].
RGD peptide conjugated self-emitting quantum dots can be used for specific integrins highly expressed in tumors. The targeted nanoparticle has been examined for complex imaging competence, like imaging various molecular targets using different spectral emissions specific nanoparticles. Recently, nanotechnology has been used for imaging metastatic tumor cells in circulation, tumor cells, and their vasculature, stem cells, and lymph nodes [48]. Che et al. designed shortwave infrared window (SWIR)-responsive QDs for bone-specific real-time in vivo and ex vivo imaging and could visualize the significant bone structures Balb/C nude and Balb/C mouse [49]. The use of specific nanoparticles can help accurately decipher and image the gram-negative and gram-positive bacteria. Due to their fluorescence characteristics and specific bacterial cell wall interactions, they can be used in a wash-free fashion in bacterial imaging, which is significant for health care, food processing, and medical hygiene.
4.5 Application of nanoparticles in theranostics
Theranostic NMs are designed by the consolidation of diagnostic and therapeutic abilities in one biodegradable nanoparticle [50]. Novel theranostic materials should have the following properties; i) highly compatible with biological entities, ii) proficiently and precisely accumulate in desired morbid tissue, iii) describe the biochemical and morphological attributes of maladies, iv) exhibit minimal toxicological effects, v) and deliver a sufficient amount of therapeutic agent. Several techniques have been used to functionalize the surface of nanoparticles for theranostics use. Surface functionalization may include imaging agents, drugs, therapeutic cargo, nucleic acid, and contrast agents by either chemical functionalization or by biofunctionalization. Chemical functionalization depends on chemical cross-linking, while biofunctionalization of nanoparticles relies on bioinspired ligands obtained from natural phytochemicals). The use of nanotechnology offers a promising alternative for the diagnosis of various cancers. Various investigations convey that nanoparticles could be engineered for advanced diagnostic agents to detect cancers [51]. Double drug encapsulated liposomes can be functionalized to enhance theranostic efficacy [51, 52]. Multifunctional Metal nanoparticles can serve as a unique platform for cancer theranostics. The range of use of metal nanoparticles includes MRI imaging, biological catalysis, magnetic hyperthermia, magnetic drug delivery, photo-responsive drug delivery, and cell separation. Metal nanoparticles, including, Polymer-NP constructs containing Gd3+ complexes, Fe3 + − terpyridine complexes, and polymeric shell-based contrast agents, are widely studied for their theranostic use as MRI contrast. Magnetic particle imaging (MPI), a novel imaging technique, is based on the analysis of iron oxide NPs in response to a magnetic field.
Cheng et al. used GE11, a novel peptide with EGFR binding affinity and complexed with doxorubicin-loaded liposomes, and observed higher liposomal uptake and accumulation than, unconjugated liposomes using NIRF [53]. In another study Song et al. designed a multifunctional targeting liposome for targeting lung cancer. Octreotide (OCT), a synthetic 8-peptide analog of somatostatin, was used to surface coat the liposome for enhanced binding with the somatostatin receptors overexpressed in a subset of tumors. Double anti-cancer drug (Honokiol and epirubicin) co-encapsulated liposomes showed enhanced OCT- somatostatin receptor binding and in vivo response [54]. Cittadino et al. designed a theranostic long-circulating liposome with co-loaded prednisolone phosphate and an amphiphilic paramagnetic gadolinium contrast agent [Gd-DOTAMA(C18)(2)] for MRI monitoring of melanoma. The theranostically engineered liposomes showed long-term MRI-based detection without a loss in drug action [51]. The theranostic nanoparticle could assist in the patient’s pre-selection, a prediction for responding to nanomedicine therapy. Moreover, nanomedicine-treated patients could be monitored throughout treatment duration while using nanomedicine formulations [39].
5. Biosafety and bioethics issues in handling mammalian cells
Biosafety is a notion that requires protecting human health and the surroundings of pathogenic and genetically modified mammalian cells or organisms used in the research. Mammalian cell culture is identified as a shelter for infectious etiologic substances, and it should change the compliance with containment measures recommended for the etiologic agent itself. The utility of cell cultures comes under the preview of a range of regulatory provisions that consider the estimation of biological risks. Genetically modified mammalian cell cultures were used in different continents; in that case, a bio-safety assessment should be regulated. The major guidelines issued to mitigate the biological risks for the users and environment are mainly by the World Health Organization; the Centers for Disease Control and Prevention, and the Swiss Expert Committee for Biosafety. Several countries or geographical zones have different directives; for example, in Europe, genetically modified research was brought into the regulatory provision (Directive 2009/41/EC). Mammalian cell culturing activities focusing on developing pharmaceutical drugs are covered by the Regulation (EC) No 726/2004 and its amendment laying down actions for the authorization and direction of medicinal goods for human and animal use. 3D cultures, especially organoid culture systems, are regularly used for disease modeling and studying nanomaterial-based physiological effects. Human Pluripotent stem cell-derived organoids are being generated from various human cell types and need better bio-safety and bioethics assessment. It must be ascertained that rules focusing on extenuating the biological risks for laboratory researchers, public health, and the environment falls under the preview one or several regulatory provisions based on biological risk assessment. Here, we are going to address the bio-safety issues involving mammalian cell cultures.
5.1 Bio-safety assessments of mammalian cell cultures
Biosafety refers to the way of protecting scientists, the health of other humans, and the environment from the probable side effects of microorganism, pathogenic, and genetically modified organisms and cells from human and mouse backgrounds. Laboratory biosafety uses safety principles and techniques to minimize the health hazard from accidental exposure or unplanned spillage while using infectious agents, toxins and other biological hazards in the laboratory setting. The bio-safety assessments applied to mammalian cells depend on a systematic assessment of the intrinsic attributes of the mammalian cultures like genetically modified cells and contaminated or intentionally infected with pathogens. Figure 2 shows a summary of the biosafety assessment and management process that is followed while handling cell culture-based experiments. This also considers an exposure analysis, which means that type of exploitation carried out with the cultures should be considered. The risk analysis of cell cultures that carry the pathogens follows the same methods for analyzing pathogens themselves. Primarily, the inclusive depiction of major pathogens is measured by the subsequent guidelines (i) pathogenicity and the infectious dose (ii) mode of transmission, (iii) host range, (iv) the epidemiology, potential reservoir and vectors, and the ability to zoonosis (v) the stability and the resilience of the pathogens in the surroundings.
Figure 2.
Flow diagram illustrating the summarizing the biosafety assessment and management process while handling cell culture-based experiments. Flow chart is inspired by reference [55].
Moreover, information related to the physicochemical properties of the pathogenic organism is considered, such as (i) susceptibility to disinfectants, (ii) physical inactivation, and (iii) drug susceptibility (e.g., sensitivity and known resistance to antibiotics or antiviral compounds). Lastly, aspects related to the disease caused by the pathogen are also to be taken into consideration. This includes (i) the availability of effective prophylaxis, (ii) the availability of efficient therapy, and (iii) any reported case of laboratory-acquired infections (LAIs). Even though underemphasized, several LAIs of mammalian cell cultures (or having virus suspension) has appeared. Among all, the exposure to vaccinia viruses amplified in mammalian cell cultures causes infections to laboratory researchers. Guidelines have been developed recently to work cautiously with vaccinia viruses and take a count of LAIs relating to this virus [55].
Understanding and having a complete analysis of the intrinsic infections of cell cultures help to perform well and safe mammalian cell culture. To assess biological risks connected with the mammalian cell cultures, three intrinsic properties related to cell cultures should be considered: the species of origin, the cell type or type of tissue (the organ of origin of the cell line), and the status of the culture. Correspondingly, mammalian cells other than human cells render less risk; still, some infectious agents are proficient at crossing one species to another species, leading to zoonosis. Highly reported infections of viruses comprise hantavirus, hemorrhagic fever viruses, bird Influenza virus, and severe acute respiratory syndrome (SARS) associated virus. Primary cell cultures are created from organ tissues. Highly characterized mammalian cells give the lowest risks compared to primary cultures or less characterized cell lines. Mammalian cells originating from different laboratories without having any proof of identity may cause cross-contamination and pathogen spreading problems, and thereby proper risk assessment and cell characterization are warranted [55, 56]. Several techniques are available for the bio-safety assessment, like RT-PCR, flow cytometry, cytogenetic analysis, DNA fingerprinting, and iso-enzyme analysis. Adventitious contagions of mammalian cell cultures are a vital problem for any activity that involves cell culturing. Contamination agents for cell cultures are bacteria, fungi, mycoplasms, parasites, viruses, prions, and even other animal cells. Modulated experimental results suggest that they spoil the cell cultures. Bio-safety point of view modified mammalian cell cultures for laboratory research, production purposes, or diagnosis purposes they may give support for contaminating materials that cause harm to human health.
5.2 Bioethics and mammalian cell culture
The futuristic technologies in bio-medicine are changing the current concepts and opening up new dimensions. Interestingly as new optimistic channels are opening and expanding, the issues of bioethics are becoming accurate and pertinent. Bioethics is the use of ethical principles in the field of medicine and healthcare. The rational application of ethics in evaluating mammalian cell culture-based experiments is highly warranted, especially during the emerging waves of change in biomedicine. Increased International cross-connection to facilitate open discussion in bioethics and related fields across cross-cultural aspects in bioethics is vital [57]. Several relevant questions arise regarding the private and sensitive use of source data for cells, moral concerns regarding the uses of embryonic and fetal tissue, genetic manipulation, gene therapy, mixing of animal and human cells, tissue banking, legal and intellectual properties associated with ex vivo tissue-engineered cell-based products, an extension of human-ness, etc.
Regarding the humane use of animals, the National Institutes of Health has issued policies as mentioned in the Public Health Service Policy on Humane Care and Use of Laboratory Animals. FDA Human Tissue Task Force and the Center for Biologics Evaluation and Research (CBER) regulates the use of human cells or tissue for implantation, transplantation, infusion, or transfer into a human recipient. The International Society for Stem Cell Research (ISSCR) has also released guidelines for stem cell research and clinical translation. The United States Congress and state legislatures are instrumental in creating laws concerning bioethics. Several professional bioethics organizations, including the American Society for Bioethics and Humanities, American Society for Law, Medicine, and Ethics, Canadian Bioethics Society, provide a platform for discussion over bioethics [57]. Several public institutions supported by academicians and researcher-based initiative for propagating public dialog plays a vital role in educating the masses.
6. Significance of IPR on industrial and academic scale
Intellectual property rights (IPR) prevail in any primitive design of the human brain, such as methodical design. IPR mentions the lawful rights agreed to the designer for guarding his innovation for a definite period. These lawful rights grant special rights to the originator or his lender to exploit his idea for a specific period. It is well established that IPR participates in the financial system. It is furthermore overwhelmingly recognized that the intellectualism linked with the originality must be agreed due to value so that products come out of intelligence. The importance of the producer of the technology has turn into lofty and consequently guard the information against unauthorized persons, the use has become a measure, at least sometimes, that would make sure revitalization of the research, investments in developing the technology. IPR helps to look after funds, time, capital, endeavor invested by the producer of an intellectual idea; as a result, IPR, in this way, encourages the profitable encouragement of a realm by encouraging positive competition and heartening trade and industry [58].
The industries have reputations in discussions about IPR strategies, and they are in the face line for controversies about the association among IPRs, R&D incentives, cost, and right to use to supplies [59]. Although, some discussions on the critical issue are relatively little practical proof to support developing IPR policy. This experimental evidence on IP and products inspect practical issues are the primary sources of the data. The industrial sector is composite and much synchronized in the majority of economies. Looking cross-nationally, the contrast among the countries in their perspective on these essential policy affairs generates some additional provocations. In a cosmopolitan industry having control over research and development conveniences in many countries, anticipating a successful transnational technology, goods are raised and developed internationally and are commercialized worldwide. Still, retails are nationalized, with no considerable uniformity across the nations in IPR authorities and various public health care organizations. IPRs may shore up significant discrepancies to price across the nations in returns and demand to prices. These discrepancies in the prices may potentially develop new local and global disagreements. Prominently, for any nation, the essential exchange in IPR regulation options is incredibly dependent on the organizations and function of its health care system.
While having a commendable collaboration, the complete fulfillment of a patent portfolio is to give equal rights for industry and academic institutions. In many countries, research organizations pursuing research in academic institutions, despite their most important work in society as a generator of the intellectual idea, the main concern is to be to deal with IP in a proficient mode. All academic institutions must become accustomed to this development to successfully fulfill the responsibility entrusted to a national or regional innovation ecosystem.
On the supply side, goods safety, supervision of manufacturing, and legal frameworks leading technology transfer among public-funded academic institutions and money-making industries playing an equal role in determining competition. Providing IPR policy to academic institutions has a favorable outcome and various settlements for shareholders. The most significant overarching advantage of these IPR policies was pronounced increases involvement in improving the global innovation performance, i.e., ultimately leading to improving the marketable products and processes. The development of spin-out companies from universities is also growing at a faster rate. The critical part is that the university should own the background IP. Then a resource of external financial support is necessary to finance the start-up company. IPR affairs at academic institutions glow enormous meandering return impending for the national economy. Publishing articles regarding innovations play an essential role in the profession of academic scientists. Participating in knowledge transfer from academia to manufacturing industries can promote academic entrepreneurship. Moreover, these patents have precious information than other publishing articles. Thus, utilizing and increasing patent writing might be beneficial in scientific research. Appropriate IPR policies and tractable technology transfer professionals play a pivotal role in streamlining the necessary work-frame. Published patents improve the economy and reputation of the academic institutions as well as the researchers.
7. Conclusion
Nanomaterials, due to their nano-size and unique physicochemical properties, have contributed significantly to the advance of biomedicine. The scope of nanomedicine also relies on the intelligent engineering of different nanoparticles with tunable attributes to modulate their nano-bio communications for biomedical applications. Elucidation of nanoparticle interactions with biological systems will help find favorable physicochemical properties to enhance biocompatibility and therapeutic efficacy with no adverse effects. A complete toxicological evaluation of engineered nanomaterials is still inadequately understood, restraining the successful translation of nanomedicine. Nanoparticle surface functionalization with specific targeting moieties can effectively develop ideal nanoparticle delivery systems for various biomedical applications and targeted therapeutics. Hence, in vitro 2D and 3D cell culture systems can accelerate biocompatibility and biotoxicity studies to drive the disease-specific application of nanoparticles [60]. Nanoparticles are progressively used in a wide variety of cell and tissue-specific biological analyses, including cell analysis, in vivo imaging, biosensors, and theranostics. Hence the issue of biosafety and bioethics has become a vital issue while using mammalian cell cultures. This chapter summarizes the critical aspects of biosafety and bioethics associated with nanomaterial-associated studies.
In conclusion, MCC is an essential tool in modern-day biomedicine, and its applications are countless in the diagnosis and therapy of human diseases. Cell culture procedures are reliable, reproducible, and unbiased, but culturing the cells is complex at times. The vast opportunities to employ MCC procedures to address rudimentary and translational research queries have elucidated the essential attentions for setting up a cell culture laboratory. Especially 3D organoid culture methods have created a cellular environment that mimics the in vivo environment.
Genome sequencing, mapping, and annotating its genetic code have become a priority in biotechnology, especially intending to understand the interaction of nanoparticles and mammalian cells. Reporting and cataloging the identified gene sequences can be critical for the progress of science and also for disease-specific therapeutics. Nanotechnology-based research has contributed significantly to many scientific fields and associated industries. Hence nanotechnology, combined with the mammalian cell culture system, can result in a research solution and can deliver considerable benefits to society at large. Hence the importance of intellectual property rights for protecting the innovator’s right over the discovery. A good understanding of the IPR policies and technology transfer protocol is vital. Academic institutions and government organizations can assist in creating a congenial platform for efficient policy management. A deeper understanding of nanoparticle-cell interaction and the design of futuristic nanocarriers can open up an era of next-generation therapeutics and theranostics.
Acknowledgments
M.K.P. acknowledges Professors S. Dubinett, B. Gomperts, and V. Hartenstein from UCLA for providing constant support and mentoring.
Conflicts of interest
The authors declare no conflict of interest. The authors have no other pertinent affiliations or financial connection with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Author contributions
Conceptualization - MKP; writing original draft preparation - HR, AM, MKP; Review and editing - MKP.
Funding
No funds available.
Abbreviations
CBER
Centre for Biologics Evaluation and Research
CT
Computed Tomography
EGFR
Epidermal Growth Factor Receptor
EPR
Enhanced Permeability and Retention
FGFR
Fibroblast Growth Factor Receptor
HUVEC
Human Umbilical Vein Endothelial Cells
IgM
Immunoglobulin M
IPR
Intellectual Property Rights
ISSCR
International Society for Stem Cell Research
LAIs
Laboratory-Acquired Infections
MMPs
Matrix Metalloproteases
MPI
Magnetic Particle imaging
MRI
Magnetic Resonance Imaging
NIH
National Institutes of Health
NMs
Nanomaterials
NPs
Nanoparticles
NRIF
Near-infrared Fluorescence
NT
Nanotechnology
OCT
Octreotide
PEG
Polyethylene glycol
PET
Positron Emission Tomography
QD
Quantum Dots
SARS
Severe Acute Respiratory Syndrome
SPECT
Single-photon Emission Computed Tomography
SRA
Sequence Read Archive
SWIR
Shortwave Infrared
TME
Tumor Microenvironment
US
Ultrasonography
USFDA
United States Food and Drug Administration
VCAM-1
Vascular Cell Adhesion Molecules-1
VEGFR
Vascular Endothelial Growth Factor Receptors
\n',keywords:"nanotechnology, intellectual property right, mammalian cell culture, nanoparticle biocompatibility, targeted drug delivery, bioethics",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78812.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78812.xml",downloadPdfUrl:"/chapter/pdf-download/78812",previewPdfUrl:"/chapter/pdf-preview/78812",totalDownloads:145,totalViews:0,totalCrossrefCites:1,dateSubmitted:"March 20th 2021",dateReviewed:"June 29th 2021",datePrePublished:"September 29th 2021",datePublished:"June 15th 2022",dateFinished:"September 29th 2021",readingETA:"0",abstract:"The significant challenges faced by modern-day medicine include designing a target-specific drug delivery system with a controlled release mechanism, having the potential to avoid opsonization and reduce bio-toxicity. Nanoparticles are materials with nanoscale dimensions and maybe natural and synthetic in origin. Engineered nano-sized materials are playing an indispensable role in the field of nanomedicine and nanobiotechnology. Besides, engineered nano-sized particles impart therapeutic applications with enhanced specificity because of their unique bespoke properties. Moreover, such application-customized nanoparticles offer an enormous possibility for their compatibility with different biological molecules like proteins, genetic materials, cell membranes, and organelles at the nano-bio frame. Besides, surface functionalization with targeting moieties such as small molecule ligands, monoclonal antibodies, aptamers, cell-penetrating peptides, and proteins facilitate nanoparticle-based specific tissue targeting. This review summarizes some of the advances in nanoparticle-based therapeutics and theranostics. A better understanding of idealistic preparation methods, physicochemical attributes, surface functionalization, biocompatibility can empower the potential translation of nanomaterials from the ‘bench-to-bedside’. In modern-day medicine, engineered nanoparticles have a wide range of demands ranging from bio-imaging, theranostics, tissue engineering, sensors, drug and nucleic acid delivery, and other pharmaceuticals applications. 2D and 3D mammalian cell-based assays are widely used to model diseases, screening of drugs, drug discovery, and toxicity analyses. Recent advances in cell culture technology and associated progress in nanotechnology have enabled researchers to study a wide variety of physiologically relevant questions. This chapter explores the properties of nanoparticles, different targeted delivery methods, biological analysis, and theranostics. Moreover, this chapter also emphasizes biosafety and bioethics associated with mammalian cell culture and discusses the significance of intellectual property rights from an industrial and academic perspective.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78812",risUrl:"/chapter/ris/78812",signatures:"Harikrishnareddy Rachamalla, Anubhab Mukherjee and Manash K. Paul",book:{id:"10797",type:"book",title:"Cell Culture",subtitle:"Advanced Technology and Applications in Medical and Life Sciences",fullTitle:"Cell Culture - Advanced Technology and Applications in Medical and Life Sciences",slug:"cell-culture-advanced-technology-and-applications-in-medical-and-life-sciences",publishedDate:"June 15th 2022",bookSignature:"Xianquan Zhan",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-446-2",printIsbn:"978-1-83969-445-5",pdfIsbn:"978-1-83969-447-9",isAvailableForWebshopOrdering:!0,editors:[{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",fullName:"Manash K. Paul",slug:"manash-k.-paul",email:"paul_cancerbiotech@yahoo.co.in",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",institution:{name:"University of California Los Angeles",institutionURL:null,country:{name:"United States of America"}}},{id:"354816",title:"Dr.",name:"Harikrishnareddy",middleName:null,surname:"Rachamalla",fullName:"Harikrishnareddy Rachamalla",slug:"harikrishnareddy-rachamalla",email:"rahakrireddy@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Indian Institute of Chemical Technology",institutionURL:null,country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",fullName:"Anubhab Mukherjee",slug:"anubhab-mukherjee",email:"dranubhab@esperernutrition.com",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Compatibility of nanomaterials towards biological interactions",level:"1"},{id:"sec_2_2",title:"2.1 Tunable physicochemical attributes of nanomaterials compatible with biomedical applications",level:"2"},{id:"sec_2_3",title:"2.1.1 Nanomaterials size",level:"3"},{id:"sec_3_3",title:"2.1.2 Nanomaterials surface charge",level:"3"},{id:"sec_4_3",title:"2.1.3 Surface functionalization",level:"3"},{id:"sec_7",title:"3. Mechanism of targeted drug delivery using nano-carrier",level:"1"},{id:"sec_7_2",title:"3.1 Nanoparticle drug delivery by passive targeting",level:"2"},{id:"sec_8_2",title:"3.2 Nanoparticle-based drug delivery by active targeting",level:"2"},{id:"sec_10",title:"4. Nanomaterial and their application from biological analysis",level:"1"},{id:"sec_10_2",title:"4.1 Nanomaterial-driven faster and more accurate cell analysis",level:"2"},{id:"sec_11_2",title:"4.2 Nanomaterial and in vivo imaging",level:"2"},{id:"sec_12_2",title:"4.3 Nanoparticles as bio-sensors",level:"2"},{id:"sec_13_2",title:"4.4 Nanoparticles as imaging agents",level:"2"},{id:"sec_14_2",title:"4.5 Application of nanoparticles in theranostics",level:"2"},{id:"sec_16",title:"5. Biosafety and bioethics issues in handling mammalian cells",level:"1"},{id:"sec_16_2",title:"5.1 Bio-safety assessments of mammalian cell cultures",level:"2"},{id:"sec_17_2",title:"5.2 Bioethics and mammalian cell culture",level:"2"},{id:"sec_19",title:"6. Significance of IPR on industrial and academic scale",level:"1"},{id:"sec_20",title:"7. Conclusion",level:"1"},{id:"sec_21",title:"Acknowledgments",level:"1"},{id:"sec_26",title:"Conflicts of interest",level:"1"},{id:"sec_21",title:"Author contributions",level:"1"},{id:"sec_22",title:"Funding",level:"1"},{id:"sec_25",title:"Abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'Poon W, Kingston BR, Ouyang B, Ngo W, Chan WCW. A framework for designing delivery systems. Nat Nanotechnol 2020;15(10):819-829.[10.1038/s41565-020-0759-5]'},{id:"B2",body:'Golombek SK, May JN, Theek B, et al. Tumor targeting via EPR: Strategies to enhance patient responses. Adv Drug Deliv Rev 2018;130:17-38.[10.1016/j.addr.2018.07.007]'},{id:"B3",body:'Mukherjee S, Madamsetty VS, Bhattacharya D, Roy Chowdhury S, Paul MK, Mukherjee A. Recent Advancements of Nanomedicine in Neurodegenerative Disorders Theranostics. Advanced Functional Materials 2020;30(35).[10.1002/adfm.202003054]'},{id:"B4",body:'Freshney RI. Culture of Animal Cells.[10.1002/9780470649367]'},{id:"B5",body:'Stacey G. 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Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
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IntechOpen publishes all of the aforementioned formats in compliance with the requirements and criteria established by the European Commission for the Horizon 2020 Program.
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Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
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Metadata for all publications is also automatically deposited in IntechOpen's OAI repository, making them available through the Open Access Infrastructure for Research in Europe's (OpenAIRE) search interface further establishing our compliance.
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In other words, publishing with IntechOpen guarantees compliance.
When choosing a publication, Horizon 2020 grant recipients are encouraged to provide open access to various types of scientific publications including monographs, edited books and conference proceedings.
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IntechOpen publishes all of the aforementioned formats in compliance with the requirements and criteria established by the European Commission for the Horizon 2020 Program.
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The chapter will also address, the evolution of the materials used for fabricating microfluidic chips, and will discuss the application‐oriented pros and cons regarding especially their critical strategies and properties for devices assembly and biocompatibility, as well their potential for downstream biochemical surface modification are presented.",book:{id:"5099",slug:"advances-in-microfluidics-new-applications-in-biology-energy-and-materials-sciences",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics - New Applications in Biology, Energy, and Materials Sciences"},signatures:"Emmanuel Roy, Antoine Pallandre, Bacem Zribi, Marie‐Charlotte\nHorny, François Damien Delapierre, Andrea Cattoni, Jean Gamby\nand Anne‐Marie Haghiri‐Gosnet",authors:[{id:"45172",title:"Prof.",name:"Anne-Marie",middleName:null,surname:"Haghiri-Gosnet",slug:"anne-marie-haghiri-gosnet",fullName:"Anne-Marie Haghiri-Gosnet"}]},{id:"29686",doi:"10.5772/38072",title:"Smart Microfluidics: The Role of Stimuli- Responsive Polymers in Microfluidic Devices",slug:"smart-microfluidics-the-role-of-stimuli-responsive-polymers-in-microfluidic-devices",totalDownloads:4646,totalCrossrefCites:3,totalDimensionsCites:9,abstract:null,book:{id:"1792",slug:"advances-in-microfluidics",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics"},signatures:"Simona Argentiere, Giuseppe Gigli, Mariangela Mortato Irini Gerges and Laura Blasi",authors:[{id:"12979",title:"Prof.",name:"Giuseppe",middleName:null,surname:"Gigli",slug:"giuseppe-gigli",fullName:"Giuseppe Gigli"},{id:"115443",title:"Dr.",name:"Simona",middleName:null,surname:"Argentiere",slug:"simona-argentiere",fullName:"Simona Argentiere"},{id:"115444",title:"Dr.",name:"Laura",middleName:null,surname:"Blasi",slug:"laura-blasi",fullName:"Laura Blasi"},{id:"138512",title:"Dr.",name:"Mariangela",middleName:null,surname:"Mortato",slug:"mariangela-mortato",fullName:"Mariangela Mortato"},{id:"138513",title:"Dr.",name:"Irini",middleName:null,surname:"Gerges",slug:"irini-gerges",fullName:"Irini Gerges"}]},{id:"29682",doi:"10.5772/34690",title:"Hydrodynamic Focusing in Microfluidic Devices",slug:"hydrodynamic-focusing-in-microfluidic-devices",totalDownloads:7494,totalCrossrefCites:7,totalDimensionsCites:9,abstract:null,book:{id:"1792",slug:"advances-in-microfluidics",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics"},signatures:"Marek Dziubinski",authors:[{id:"101230",title:"Prof.",name:"Marek",middleName:"Stanislaw",surname:"Dziubinski",slug:"marek-dziubinski",fullName:"Marek Dziubinski"}]},{id:"51264",doi:"10.5772/64284",title:"Microfluidics in CO2 Capture, Sequestration, and Applications",slug:"microfluidics-in-co2-capture-sequestration-and-applications",totalDownloads:2008,totalCrossrefCites:5,totalDimensionsCites:7,abstract:"The abnormal climate change has made the reduction of CO2 emission that received worldwide attention. The integration of CO2 capture-sequestration application for enhanced oil recovery (EOR) technology will be the new trend. Several scholars have applied microfluidics in CO2 capture, oil and gas analysis, and CO2 sequestration. The mass transfer process for CO2 capture can be intensified owing to the large specific surface/volume ratio and high contact area in microchannels. The small amount of feeding volumes of oil and gas samples and the quick response for the analysis make the microfluidics a promising tool for the oil and gas analysis. Moreover, microfluidics can reveal the transport mechanism at microscale for multiphase interfacial phenomena in microchannels within porous media during the CO2 flooding process in line with the pressure, temperature, and material properties of the rock within the oil reservoir. This chapter will elaborate the progress of the application of microfluidic technology in the utilization of CO2, including the mechanism of mass transfer for CO2 in microreactors, the advantages of microfluidics in oil and gas analysis, and the fundamentals of microfluidics in CO2 flooding, oil recovery improvement, and CO2 sequestration.",book:{id:"5099",slug:"advances-in-microfluidics-new-applications-in-biology-energy-and-materials-sciences",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics - New Applications in Biology, Energy, and Materials Sciences"},signatures:"Taotao Fu",authors:[{id:"177065",title:"Associate Prof.",name:"Taotao",middleName:null,surname:"Fu",slug:"taotao-fu",fullName:"Taotao Fu"}]}],mostDownloadedChaptersLast30Days:[{id:"51263",title:"High and Efficient Production of Nanomaterials by Microfluidic Reactor Approaches",slug:"high-and-efficient-production-of-nanomaterials-by-microfluidic-reactor-approaches",totalDownloads:2647,totalCrossrefCites:5,totalDimensionsCites:15,abstract:"This chapter overviews different approaches for the synthesis of nanostructured materials based on alternative methodologies to the most conventional and widespread colloidal wet chemical route and with a great potential applicability to large-scale and continuous production of nanomaterials. Their major outcomes, current progress in synthesis of micro and nanostructures by using microfluidics techniques and potential applications for the next future are reviewed throughout three different sections. Emphasis is placed on nanomaterials production basics, nanomaterials production techniques and microfluidic reactors (types, materials, designs). The integration of nanoparticle and microreactor technologies delivers enormous possibilities for the further development of novel materials and reactors. In this chapter, recent achievements in the synthesis of nanoparticles in microfluidic reactors are stated. A variety of strategies for synthesizing inorganic and polymeric nanoparticles are presented and compared, including continuous flow, gas–liquid segmented flow and droplet-based microreactors",book:{id:"5099",slug:"advances-in-microfluidics-new-applications-in-biology-energy-and-materials-sciences",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics - New Applications in Biology, Energy, and Materials Sciences"},signatures:"Victor Sebastian Cabeza",authors:[{id:"177071",title:"Dr.",name:"Victor",middleName:null,surname:"Sebastian",slug:"victor-sebastian",fullName:"Victor Sebastian"}]},{id:"52333",title:"Advances in Low Volume Sample Analysis Using Microfluidic Separation Techniques",slug:"advances-in-low-volume-sample-analysis-using-microfluidic-separation-techniques",totalDownloads:1749,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"During the last decades, a great interest has been shown for miniaturised separation techniques. The use of microfluidic techniques fulfills the constant needs for increasing sample throughput and analysis sensitivity, while reducing costs and sample volume consumption. In this chapter, three microfluidic separation techniques will be addressed: capillary electrophoresis, gas chromatography and liquid chromatography. A special attention will be paid to miniaturised liquid chromatography, with a deep investigation of its advantages compared with classical liquid chromatography. Sample preparation adapted to low volumes (a few µl) will also be discussed.",book:{id:"5099",slug:"advances-in-microfluidics-new-applications-in-biology-energy-and-materials-sciences",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics - New Applications in Biology, Energy, and Materials Sciences"},signatures:"Virginie Houbart and Marianne Fillet",authors:[{id:"177056",title:"Prof.",name:"Marianne",middleName:null,surname:"Fillet",slug:"marianne-fillet",fullName:"Marianne Fillet"}]},{id:"29687",title:"Robust Extraction Interface for Coupling Droplet-Based and Continuous Flow Microfluidics",slug:"robust-extraction-interface-for-coupling-droplet-based-and-continuous-flow-microfluidics",totalDownloads:2290,totalCrossrefCites:0,totalDimensionsCites:1,abstract:null,book:{id:"1792",slug:"advances-in-microfluidics",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics"},signatures:"Xuefei Sun, Keqi Tang, Richard D. Smith and Ryan T. Kelly",authors:[{id:"111896",title:"Dr.",name:"Ryan",middleName:null,surname:"Kelly",slug:"ryan-kelly",fullName:"Ryan Kelly"},{id:"111900",title:"Dr.",name:"Xuefei",middleName:null,surname:"Sun",slug:"xuefei-sun",fullName:"Xuefei Sun"},{id:"135791",title:"Dr.",name:"Richard",middleName:null,surname:"Smith",slug:"richard-smith",fullName:"Richard Smith"},{id:"135792",title:"Dr.",name:"Keqi",middleName:null,surname:"Tang",slug:"keqi-tang",fullName:"Keqi Tang"}]},{id:"51262",title:"Electroosmotic Flow Pump",slug:"electroosmotic-flow-pump",totalDownloads:2515,totalCrossrefCites:0,totalDimensionsCites:4,abstract:"Electroosmotic flow (EOF) pumping has been widely used to manipulate fluids such as liquid sample reagents in microfluidic systems. In this chapter, we will introduce the research progress on EOF pumps in the fields of microfluidic science and technology and briefly present their microfluidic applications in recent years. The chapter focuses on pump channel materials, electrodes, and their fabrication techniques in microfluidics.",book:{id:"5099",slug:"advances-in-microfluidics-new-applications-in-biology-energy-and-materials-sciences",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics - New Applications in Biology, Energy, and Materials Sciences"},signatures:"Meng Gao and Lin Gui",authors:[{id:"176994",title:"Prof.",name:"Lin",middleName:null,surname:"Gui",slug:"lin-gui",fullName:"Lin Gui"},{id:"177064",title:"Ph.D.",name:"Meng",middleName:null,surname:"Gao",slug:"meng-gao",fullName:"Meng Gao"}]},{id:"51878",title:"Application of Microfluidics in Stem Cell Culture",slug:"application-of-microfluidics-in-stem-cell-culture",totalDownloads:2195,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"In this chapter, we review the recent developments, including our studies on the microfabricated devices applicable to stem cell culture. We will focus on the application of pluripotent stem cells including embryonic stem cells and induced pluripotent stem cells. In the first section, we provide a background on microfluidic devices, including their fabrication technology, characteristics, and the advantages of their application in stem cell culture. The second section outlines the use of micropatterning technology in stem cell culture. The use of microwell array technology in stem cell culture is explored in the third section. In the fourth section, we discuss the use of the microfluidic perfusion culture system for stem cell culture, and the last section is a summary of the current state of the art and perspectives of microfluidic technologies in stem cell culture.",book:{id:"5099",slug:"advances-in-microfluidics-new-applications-in-biology-energy-and-materials-sciences",title:"Advances in Microfluidics",fullTitle:"Advances in Microfluidics - New Applications in Biology, Energy, and Materials Sciences"},signatures:"Shinji Sugiura, Kohji Nakazawa, Toshiyuki Kanamori and Kiyoshi\nOhnuma",authors:[{id:"83549",title:"Dr.",name:"Kiyoshi",middleName:null,surname:"Ohnuma",slug:"kiyoshi-ohnuma",fullName:"Kiyoshi Ohnuma"},{id:"177083",title:"Dr.",name:"Shinji",middleName:null,surname:"Sugiura",slug:"shinji-sugiura",fullName:"Shinji Sugiura"},{id:"177084",title:"Prof.",name:"Kohji",middleName:null,surname:"Nakazawa",slug:"kohji-nakazawa",fullName:"Kohji Nakazawa"},{id:"177085",title:"Dr.",name:"Toshiyuki",middleName:null,surname:"Kanamori",slug:"toshiyuki-kanamori",fullName:"Toshiyuki Kanamori"}]}],onlineFirstChaptersFilter:{topicId:"697",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
\r\n
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
\r\n
\r\n\t
\r\n
\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
\r\n
\r\n\t
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"June 23rd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. 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She serves as an Associate Editor for the International Journal of the Analytic Hierarchy Process. She is a member of AHP Academy and a member of several editorial boards. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation"},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/272683",hash:"",query:{},params:{id:"272683"},fullPath:"/profiles/272683",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()