Collagen based biomaterials for 3D printed tissues.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\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:"5493",leadTitle:null,fullTitle:"Escherichia coli - Recent Advances on Physiology, Pathogenesis and Biotechnological Applications",title:"Escherichia coli",subtitle:"Recent Advances on Physiology, Pathogenesis and Biotechnological Applications",reviewType:"peer-reviewed",abstract:"Escherichia coli is a versatile organism and very diverse. Members of this species vary from very pathogenic agents causing different types of diseases including meningitis, gastroenteritis, and septicemia, just to cite a few, to harmless organisms living in the intestines of both humans and animals. E. coli has also been used as a model organism for most bacteria except a few. For this reason, its study provides a huge advantage and can help understand the mechanisms involved in different processes such as pathogenesis, environmental disinfection, nutrient utilization, antibiotic resistance, and diagnostic/detection methods, and these are indeed the topics discussed in this book. The book has been divided into four main sections representing the different facets of E. coli applications, which include disease, biotechnology, environmental engineering and innovative approaches to detection, and lastly its physiology and cell biology. Such processes can be applied to the study of other organisms as well considering the development of diversity; for example, many organisms are capable of horizontal gene transfer, which is capable of increasing the fitness of the bacterial organisms involved and has a great impact on the control of such bacterial organism.",isbn:"978-953-51-3330-8",printIsbn:"978-953-51-3329-2",pdfIsbn:"978-953-51-4735-0",doi:"10.5772/63146",price:139,priceEur:155,priceUsd:179,slug:"-i-escherichia-coli-i-recent-advances-on-physiology-pathogenesis-and-biotechnological-applications",numberOfPages:434,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"1ef47003dd99be6a53eaa91efb882dff",bookSignature:"Amidou Samie",publishedDate:"July 12th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5493.jpg",numberOfDownloads:53374,numberOfWosCitations:8,numberOfCrossrefCitations:64,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:126,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:198,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 27th 2016",dateEndSecondStepPublish:"May 18th 2016",dateEndThirdStepPublish:"August 22nd 2016",dateEndFourthStepPublish:"November 20th 2016",dateEndFifthStepPublish:"December 20th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"52247",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/52247/images/5820_n.jpg",biography:"Dr. Amidou Samie is an associate professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at the category C2 and has published widely in the field of infectious diseases and graduated several MSc and PhD students. His research activities cover mostly topics in infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point of use water treatment technologies using nanoparticles from silver and copper in collaboration with the University of Virginia in the USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],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:"54926",title:"Enterotoxigenic and Enterohemorrhagic Escherichia coli: Survival and Modulation of Virulence in the Human Gastrointestinal Tract",doi:"10.5772/intechopen.68309",slug:"enterotoxigenic-and-enterohemorrhagic-i-escherichia-coli-i-survival-and-modulation-of-virulence-in-t",totalDownloads:2083,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Enterotoxigenic Escherichia coli (ETEC) and Enterohemorrhagic Escherichia coli (EHEC) are major food‐ and water‐borne pathogens that constitute a serious public health threat in low‐income and developed countries, respectively. Survival and expression of virulence genes in the human digestive tract are key features in bacterial pathogenesis, but the mechanisms behind these processes remain largely unknown due to obvious prohibition of human studies. Use of well‐controlled and multi‐parametric in vitro models can aid in addressing knowledge gaps in ETEC and EHEC pathogenesis. After a general description of the physiopathology of ETEC and EHEC infections, this chapter will give an overview of all the in vitro studies that have investigated the effect of the main physicochemical and biotic parameters of the human gut on pathogen survival and expression of virulence factors. We bring a picture of how ETEC and EHEC are able to adapt to each of the successive environments of the human gastrointestinal tract by reading many cues provided by both the host and the gut microbiota.",signatures:"Charlène Roussel, Charlotte Cordonnier, Valérie Livrelli, Tom Van de\nWiele and Stéphanie Blanquet‐Diot",downloadPdfUrl:"/chapter/pdf-download/54926",previewPdfUrl:"/chapter/pdf-preview/54926",authors:[{id:"120350",title:"Prof.",name:"Tom",surname:"Van De Wiele",slug:"tom-van-de-wiele",fullName:"Tom Van De Wiele"},{id:"191864",title:"Dr.",name:"Stéphanie",surname:"Blanquet-Diot",slug:"stephanie-blanquet-diot",fullName:"Stéphanie Blanquet-Diot"},{id:"191866",title:"Mrs.",name:"Charlène",surname:"Roussel",slug:"charlene-roussel",fullName:"Charlène Roussel"},{id:"191867",title:"Dr.",name:"Charlotte",surname:"Cordonnier",slug:"charlotte-cordonnier",fullName:"Charlotte Cordonnier"},{id:"197027",title:"Prof.",name:"Valérie",surname:"Livrelli",slug:"valerie-livrelli",fullName:"Valérie Livrelli"}],corrections:null},{id:"54475",title:"Virulence Factors and Innovative Strategies for the Treatment and Control of Uropathogenic Escherichia coli",doi:"10.5772/67778",slug:"virulence-factors-and-innovative-strategies-for-the-treatment-and-control-of-uropathogenic-i-escheri",totalDownloads:1547,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Urinary tract infections (UTIs) are considered to be the most frequent bacterial infections. Escherichia coli is the major factor of community-acquired UTI (80–90%) and a large part of nosocomial UTI (30%), including cystitis, pyelonephritis, prostatitis, and asymptomatic bacteriuria. Uropathogenic E. coli (UPEC) shows a variety of virulence factors that allow their transition from the intestinal tract to the urinary tract and causing infection. The virulence factors responsible for pathogenesis outside the gastrointestinal tract belong to various functional groups. Antimicrobial resistance among E. coli causing UTIs is increasing in many countries around the world. This paper presents key virulence factors of UPEC such as adhesins, toxins, iron acquisition systems, and biofilm formation by UPEC, which are major problems in patients with long-term catheterization. The resistance of UPEC to antibiotics and innovative strategies of treatment and control of UPEC including drug therapy, preventive vaccines, probiotics, cranberry as source of antimicrobial metabolites, bacteriophages, new therapeutic antibiofilm treatment such as engineered phages, nanoparticles, and plant-derived antibacterial agents are also presented.",signatures:"Barbara Kot",downloadPdfUrl:"/chapter/pdf-download/54475",previewPdfUrl:"/chapter/pdf-preview/54475",authors:[{id:"189685",title:"Associate Prof.",name:"Barbara",surname:"Kot",slug:"barbara-kot",fullName:"Barbara Kot"}],corrections:null},{id:"56154",title:"The Pathogenesis of Escherichia coli Urinary Tract Infection",doi:"10.5772/intechopen.69030",slug:"the-pathogenesis-of-i-escherichia-coli-i-urinary-tract-infection",totalDownloads:3854,totalCrossrefCites:4,totalDimensionsCites:6,hasAltmetrics:1,abstract:"Urinary tract infections (UTIs) are the commonest human bacterial infections and are responsible for substantial morbidity and mortality, resulting in increased healthcare costs. Most UTIs are caused by specialized Escherichia coli (E. coli) strains referred to as uropathogenic E. coli (UPEC). UPEC possess a variety of virulence factors (VFs), which the organism uses to attach, invade, and injure the host. These VFs include adhesins, toxins, iron acquisition factors, lipopolysacharide capsules, and other invasins. Most studies on UTI pathogenesis have targeted VFs. The source of UPEC is the host’s fecal flora. According to the pathogenicity theory, UPEC strains with special VFs move from the host’s fecal flora to the urogenital tract and cause UTI. However, another theory states that the numerically abundant strain is responsible for UTI. Effective UTI management is hampered by the recent rise in antibiotic resistance, specifically, the recent emergence of multidrug-resistant E. coli sequence type 131. The distribution of VFs and other bacterial characteristics among different patient groups and UTI syndromes, is crucial understanding UTI pathogenesis, which would guide clinical decision making. For ST131 clonal group, further epidemiological studies are needed to clarify transmission pathways, risk factors for spread, and reservoirs, so that effective control measures can be devised.",signatures:"Timothy Kudinha",downloadPdfUrl:"/chapter/pdf-download/56154",previewPdfUrl:"/chapter/pdf-preview/56154",authors:[{id:"192136",title:"Dr.",name:"Timothy",surname:"Kudinha",slug:"timothy-kudinha",fullName:"Timothy Kudinha"}],corrections:null},{id:"54978",title:"Effect of Uropathogenic Escherichia coli on Human Sperm Function and Male Fertility",doi:"10.5772/intechopen.68312",slug:"effect-of-uropathogenic-i-escherichia-coli-i-on-human-sperm-function-and-male-fertility",totalDownloads:1578,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Infections of the reproductive tract represent nearly 15% of male infertility cases. The most frequently isolated bacterium in the ejaculate of infertile men is Escherichia coli (E. coli), which causes between 60 and 85% of cases of chronic bacterial prostatitis leading to sperm damage. The aim of this chapter is to discuss the negative effects of E. coli on sperm quality and male fertility. The E. coli isolated from semen is uropathogenic (UPEC) and can damage sperm in different ways. UPEC induces activation of polymorphonuclear leukocytes with the release of cytokines and reactive oxygen species, the latter being harmful due to their ability to induce lipid peroxidation and early sperm capacitation. Also, UPEC decreases sperm motility, vitality and mitochondrial membrane potential through direct contact or mediated by its soluble metabolites. The negative effects are higher with strains with specific characteristics such as hemolytic capacity. In vivo studies with mice models have shown that UPEC inoculated into the epididymis induces inflammatory damage with testicular mass decrease and low sperm concentration. Future studies are needed to clarify the molecular mechanisms by which E. coli damages sperm. This knowledge will make it possible to take measures to avoid deleterious consequences on the fertilizing potential of men.",signatures:"Juana V. Villegas, Rodrigo Boguen and Pamela Uribe",downloadPdfUrl:"/chapter/pdf-download/54978",previewPdfUrl:"/chapter/pdf-preview/54978",authors:[{id:"191444",title:"Dr.",name:"Juana V.",surname:"Villegas",slug:"juana-v.-villegas",fullName:"Juana V. Villegas"},{id:"191447",title:"Dr.",name:"Rodrigo",surname:"Boguen",slug:"rodrigo-boguen",fullName:"Rodrigo Boguen"},{id:"192019",title:"Dr.",name:"Pamela",surname:"Uribe",slug:"pamela-uribe",fullName:"Pamela Uribe"}],corrections:null},{id:"54056",title:"Antimicrobial Mechanisms of Escherichia coli",doi:"10.5772/67363",slug:"antimicrobial-mechanisms-of-i-escherichia-coli-i-",totalDownloads:2531,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Increasing antimicrobial resistance in strains of Escherichia coli is having a major impact on the healthcare industry worldwide. The appearance of extended-spectrum β-lactamase (ESBL) and carbapenem-resistant Enterobacteriaceae (CRE) strains has caused clinicians to worry that these strains might become as deadly as methicillin-resistant Staphylococcus aureus (MRSA) strains. It is vital that physicians have resources available to help keep them updated on these bacteria and the potential impact on healthcare. This chapter reviews the major strains of E. coli (intestinal and urinary), along with a review of the virulence factors, main diseases caused, and pertinent pathogenesis. The chapter then discusses antimicrobial therapy, what drugs are effective against these E. coli strains, and the development of resistance to these specific drug classes. Lastly, the molecular aspects of antimicrobial resistance mechanisms in this organism are discussed. This information will be especially helpful for physicians in providing them with a concise review of E. coli and an understanding of what is involved in antimicrobial resistance. Hopefully this information can be used to improve the outcomes for patients with E. coli infections.",signatures:"Wanda C. Reygaert",downloadPdfUrl:"/chapter/pdf-download/54056",previewPdfUrl:"/chapter/pdf-preview/54056",authors:[{id:"190201",title:"Dr.",name:"Wanda",surname:"Reygaert",slug:"wanda-reygaert",fullName:"Wanda Reygaert"}],corrections:null},{id:"54220",title:"Antibiotic Resistance among Escherichia coli: Isolates and Novel Approaches to the Control of E. coli Infections",doi:"10.5772/67400",slug:"antibiotic-resistance-among-i-escherichia-coli-i-isolates-and-novel-approaches-to-the-control-of-i-e",totalDownloads:2478,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Bacteria are the microorganisms that most frequently cause infectious diseases in humans. The synthesis of silver nanoparticles (AgNPs) has attracted interest due to the new and different physical and chemical characteristics with applications in new fields. AgNPs, alone or supported on ceramic, are used as antimicrobial fillers in textiles and polymers for food-packaging and biomedical applications, for antimicrobial paints, and potentially for drug delivery. The evaluation of mesoporous nanostructures or nanocomposites as FDU-12/lignin/silver was effective in inhibiting Staphylococcus aureus, E. coli, Enterococcus faecalis, and Candida albicans. The best results were achieved against the inhibition of E. coli and with the structures FDU-12/silver. In plates with FDU-12/lignin/silver, FDU-12, FDU-12/lignin, and the positive control, it was enumerated at 0, 6, 14, and 27 colonies, respectively. While the development of resistance to a new antibiotic is expected, the time course and degree of resistance are uncertain and depend on various factors. The application of AgNPs as nanocomposites can alter the expression of bacterial proteins and could be used for inactivation. This review explores such aspects and a number of factors arising like the use of nanostructures against E. coli, from the knowledge acquired.",signatures:"Henrique C. Alves, Felipe de P. N. Cruz, Pamela C. P. de Assis, José D.\nC. Pessoa, Luis C. Trevelin, Angela M. de O. Leal and Cristina P. de\nSousa",downloadPdfUrl:"/chapter/pdf-download/54220",previewPdfUrl:"/chapter/pdf-preview/54220",authors:[{id:"192008",title:"Associate Prof.",name:"Cristina",surname:"Paiva De Sousa",slug:"cristina-paiva-de-sousa",fullName:"Cristina Paiva De Sousa"},{id:"192009",title:"Dr.",name:"Henrique",surname:"Cezar Alves",slug:"henrique-cezar-alves",fullName:"Henrique Cezar Alves"},{id:"192010",title:"Dr.",name:"Jose Dalton",surname:"Cruz Pessoa",slug:"jose-dalton-cruz-pessoa",fullName:"Jose Dalton Cruz Pessoa"},{id:"192011",title:"Prof.",name:"Luis Carlos",surname:"Trevelin",slug:"luis-carlos-trevelin",fullName:"Luis Carlos Trevelin"},{id:"192012",title:"Prof.",name:"Angela",surname:"Merici De Oliveira Leal",slug:"angela-merici-de-oliveira-leal",fullName:"Angela Merici De Oliveira Leal"},{id:"195264",title:"Dr.",name:"Felipe",surname:"de Paula Nogueira Cruz",slug:"felipe-de-paula-nogueira-cruz",fullName:"Felipe de Paula Nogueira Cruz"},{id:"195370",title:"BSc.",name:"Pamela Carla",surname:"Pereira De Assis",slug:"pamela-carla-pereira-de-assis",fullName:"Pamela Carla Pereira De Assis"}],corrections:null},{id:"53957",title:"E. coli as an Indicator of Contamination and Health Risk in Environmental Waters",doi:"10.5772/67330",slug:"-i-e-coli-i-as-an-indicator-of-contamination-and-health-risk-in-environmental-waters",totalDownloads:3033,totalCrossrefCites:6,totalDimensionsCites:10,hasAltmetrics:1,abstract:"Good public health depends on regular monitoring of water quality as faecal contamination is a serious problem due to the potential for contracting disease. Bacterial contamination in water is measured using indicator organisms, notably Escherichia coli and Enterococci which are used as primary indicators of contamination in fresh and marine water quality, respectively, rather than the total coliforms present. Although most E. coli and Enterococci strains cause only mild infections, their presence is indicative of the potential presence of other more pathogenic organisms which are a danger to human health. The acceptable levels of indicator organisms are defined in legislation and are set for drinking, river, well and marine water. This chapter will consider current gold standard culture methods of analysis for E. coli and compare them with molecular DNA procedures. Established culture methods use β‐D-glucuronidase to identify E. coli and β‐D-galactosidase to detect coliforms. Emphasis will be placed on newer procedures that can be used onsite supported by laboratory procedures used for confirmation. Available rapid fluorimetric procedures which have been developed for use in the field, based on the assay of β‐D-glucuronidase, will be discussed. The rapid advances in procedures using a molecular approach will be considered and compared with the more established methods for determining E. coli in water. It is essential that all these methods should be quantitative in order to comply with legal norms, and in this regard, the potential involvement of biosensor technology will be of great value in successfully transferring laboratory procedures to the field.",signatures:"Robert G. Price and Dirk Wildeboer",downloadPdfUrl:"/chapter/pdf-download/53957",previewPdfUrl:"/chapter/pdf-preview/53957",authors:[{id:"190960",title:"Prof.",name:"Robert",surname:"Price",slug:"robert-price",fullName:"Robert Price"}],corrections:null},{id:"55322",title:"Detection Methods for Lipopolysaccharides: Past and Present",doi:"10.5772/intechopen.68311",slug:"detection-methods-for-lipopolysaccharides-past-and-present",totalDownloads:3162,totalCrossrefCites:7,totalDimensionsCites:14,hasAltmetrics:0,abstract:"Lipopolysaccharide (LPS) is the primary component of the outer membrane of Gram‐negativebacteria. LPS aids in protecting bacterial cells, and also defines the unique serogroups used to classify bacteria. Additionally, LPS is an endotoxin and the primary stimulator of innate immune cells in mammals, making it an ideal candidate for early detection of pathogens. However, the majority of methods for detection of LPS focus on detection of the endotoxic component of the molecule, lipid A. Since lipid A is largely conserved among bacterial species and serogroups, these detection approaches are highly nonspecific. Thus, the importance of identifying the O‐polysaccharide antigenic portion of LPS, which confers serogroup specificity, has received a great deal of attention in recent years. However, methods that are highly selective to the O‐antigens are typically less sensitive than those that target the endotoxin. Here we present a history and comparison of the sensitivity of these methods and their value for detecting bacteria in a variety of different sample types.",signatures:"Loreen R. Stromberg, Heather M. Mendez and Harshini Mukundan",downloadPdfUrl:"/chapter/pdf-download/55322",previewPdfUrl:"/chapter/pdf-preview/55322",authors:[{id:"45308",title:"Dr.",name:"harshini",surname:"mukundan",slug:"harshini-mukundan",fullName:"harshini mukundan"},{id:"195105",title:"Dr.",name:"Loreen",surname:"Stromberg",slug:"loreen-stromberg",fullName:"Loreen Stromberg"},{id:"195106",title:"Mrs.",name:"Heather",surname:"Mendez",slug:"heather-mendez",fullName:"Heather Mendez"}],corrections:null},{id:"54599",title:"Effect of Environmental Conditions on Escherichia coli Survival in Seawater",doi:"10.5772/67912",slug:"effect-of-environmental-conditions-on-i-escherichia-coli-i-survival-in-seawater",totalDownloads:1421,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:1,abstract:"We investigated separate and simultaneous effect of temperature, salinity and solar radiation, as well as bacterial strain and origin on Escherichia coli (E. coli) survival in seawater in experimental conditions. The experiments were carried out by placing the bottles filled with seawater of different salinity (15.0, 30.0 and 36.5 psu) and contaminated by bacterial cultures in three light‐protected air incubators set to different temperatures (6, 12, 18 and 24°C), or by placing the bottles in plastic containers filled with water of controlled temperature and exposing them to direct solar light. In experiments in the dark, two typed and two wild E. coli strains were tested. The mean T90 values were 33.55 h for E. coli ATCC 8739, 42.50 h for E. coli ATCC 35218, 72.8 h for E. coli originating from seagull feces and 278.6 h for E. coli originating from sewage, indicating differences between survival abilities among strains. The effect of temperature on T90 was significant only in seagull E. coli at 36.5 psu and sewage E. coli at 30.0 psu and was positive. The effect of salinity was significant only in seagull strain and also was positive. No interactive effect of temperature and salinity was recorded. Experiments in the presence of solar radiation, carried out with two ATCC E. coli strains, demonstrated its dominate harmful effect on bacterial cells, reducing T90 of both strains to 0.30–0.82 h for E. coli ATCC 35218 and 0.31–5.93 h for E. coli ATCC 8739. Within the ultraviolet A (UVA) and photosynthetically active radiation (PAR) spectrum of solar radiation, the wavelengths of 320–360 nm were found as most bactericidal. By comparing survival of cultivated E. coli cells to those in natural seawater samples, significantly higher survival E. coli cells in natural seawater samples was found.",signatures:"Slaven Jozić and Mladen Šolić",downloadPdfUrl:"/chapter/pdf-download/54599",previewPdfUrl:"/chapter/pdf-preview/54599",authors:[{id:"190668",title:"Dr.",name:"Slaven",surname:"Jozić",slug:"slaven-jozic",fullName:"Slaven Jozić"},{id:"193627",title:"Prof.",name:"Mladen",surname:"Šolić",slug:"mladen-solic",fullName:"Mladen Šolić"}],corrections:null},{id:"54411",title:"Isolation and Characterization of Escherichia coli from Animals, Humans, and Environment",doi:"10.5772/67390",slug:"isolation-and-characterization-of-i-escherichia-coli-i-from-animals-humans-and-environment",totalDownloads:6142,totalCrossrefCites:5,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Working on a diverse species of bacteria that have hundreds of pathotypes representing hundreds of strains and many closely related family members is a challenge. Appropriate research design is required not only to achieve valid desired outcome but also to minimize the use of resources, including time to outcome and intervention. This chapter outlines basics of Escherichia coli isolation and characterization strategies that can assist in research designing that matches the set objectives. Types of samples to be collected, collection and storage strategies, and processing of samples are described. Different approaches to isolation, confirmation and concentration of various E. coli strains are summarized in this chapter. Characterization and typing of E. coli isolates by biochemical, serological, and molecular methods have been explained so that an appropriate choice is made to suite a specific E. coli strain/pathotype. Some clues on sample and isolate preservation for future use are outlined, and general precautions regarding E. coli handling are also presented to the researcher to avoid improper planning and execution of E. coli-related research. Given different options, the best E. coli research design, however, should try as much as possible to shorten the length of time to outcomes.",signatures:"Athumani Msalale Lupindu",downloadPdfUrl:"/chapter/pdf-download/54411",previewPdfUrl:"/chapter/pdf-preview/54411",authors:[{id:"185959",title:"Dr.",name:"Athumani",surname:"Lupindu",slug:"athumani-lupindu",fullName:"Athumani Lupindu"}],corrections:null},{id:"54927",title:"Escherichia coli Inactivation Using Pressurized Carbon Dioxide as an Innovative Method for Water Disinfection",doi:"10.5772/intechopen.68310",slug:"-i-escherichia-coli-i-inactivation-using-pressurized-carbon-dioxide-as-an-innovative-method-for-wate",totalDownloads:1434,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Advanced water disinfection technologies that do not produce harmful by-products would be highly desirable. This study presents results for the use of pressurized carbon dioxide (CO2) and a liquid-film-forming apparatus for disinfection of seawater. The sensitivity of Escherichia coli to the pressurized CO2 was examined for various conditions of pressure, temperature, working volume ratios (WVRs), flow rates, and pressure cycling. Morphology of E. coli was observed by using scanning electron microscopy (SEM). A strong correlation between the E. coli inactivation efficiency and pressure cycling was detected (p < 0.001). The frequency and magnitude of pressure cycling were the key factors responsible for high rates of E. coli inactivation during the pressurized CO2 treatment. The results from linear regression analyses suggest that the model can explain about 91% of the E. coli inactivation efficiency (p < 0.001). The pressurized CO2 treatment (at 0.7 MPa, 20°C, 50% WVR) in the process involving pressure cycling (∆P = 0.12 MPa, 15 cycles) resulted in complete inactivation (5.2 log reduction) of E. coli within 3 min. These findings suggest that pressurized CO2 could be a potentially useful disinfection method for water treatment.",signatures:"Tsuyoshi Imai and Thanh-Loc Thi Dang",downloadPdfUrl:"/chapter/pdf-download/54927",previewPdfUrl:"/chapter/pdf-preview/54927",authors:[{id:"49754",title:"Prof.",name:"Tsuyoshi",surname:"Imai",slug:"tsuyoshi-imai",fullName:"Tsuyoshi Imai"},{id:"192033",title:"Dr.",name:"Thanh-Loc Thi",surname:"Dang",slug:"thanh-loc-thi-dang",fullName:"Thanh-Loc Thi Dang"}],corrections:null},{id:"54393",title:"Evaluating Meta-Analysis Research of Escherichia coli",doi:"10.5772/67337",slug:"evaluating-meta-analysis-research-of-i-escherichia-coli-i-",totalDownloads:1388,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter summarizes the progress in Escherichia coli research that used the meta-analysis approach. Using systematic searches for E. coli literature, we tracked meta-analysis publications and analyzed them based on a number of parameters. These included subject/topic (epidemiology, clinical/intervention/prevention and environmental), geographical region (the Americas, Europe and Australasia) and clinical syndrome (enteric, renal, and sepsis/meningitis). These parameters were plotted in terms of time span to obtain a sense of dynamic change or its absence through the years since the turn of the twentieth century. In terms of region, topic and syndrome, highest meta-analysis productivity was attributed to the Americas, clinical/intervention/prevention and enteric, all of which took place in the last 5 years (2011–2016). Over the combined time span of 16 years, the Americas significantly dominated meta-analysis outputs when compared to Europe and Australasia (P = 0.003). In conclusion, our findings facilitate awareness of the progress in this field wherein the studied parameters were analyzed for patterns over time and differential rates of publication productivity.",signatures:"Noel Pabalan, Eloisa Singian, Lani Tabangay and Hamdi Jarjanazi",downloadPdfUrl:"/chapter/pdf-download/54393",previewPdfUrl:"/chapter/pdf-preview/54393",authors:[{id:"190341",title:"Dr.",name:"Noel",surname:"Pabalan",slug:"noel-pabalan",fullName:"Noel Pabalan"},{id:"195013",title:"MSc.",name:"Eloisa",surname:"Singian",slug:"eloisa-singian",fullName:"Eloisa Singian"},{id:"195014",title:"Dr.",name:"Hamdi",surname:"Jarjanazi",slug:"hamdi-jarjanazi",fullName:"Hamdi Jarjanazi"},{id:"195015",title:"MSc.",name:"Lani",surname:"Tabangay",slug:"lani-tabangay",fullName:"Lani Tabangay"}],corrections:null},{id:"53916",title:"Escherichia coli as a Model Organism and Its Application in Biotechnology",doi:"10.5772/67306",slug:"-i-escherichia-coli-i-as-a-model-organism-and-its-application-in-biotechnology",totalDownloads:5618,totalCrossrefCites:10,totalDimensionsCites:30,hasAltmetrics:1,abstract:"Without a doubt, in the past 20 or so years, we have achieved the power of biology in different ways. In the present, we have many tools for developing novel technologies and applications for organism modifications that ultimately let us know many aspects of organisms’ biology and, therefore, apply that knowledge for technological purposes. Of all the model organisms and tools for genetic modification available, Escherichia coli stands out as a model organism and what we would like to call “molecular biologist tool box.” In the present chapter, we aim to review our current knowledge regarding genetic modifications and tools for modifying E. coli to generate plasmid vectors, single and multiple gene knockouts, whole genome editing, biosensor generation and applications and synthetic gene circuits and genomes.",signatures:"Vargas-Maya Naurú Idalia and Franco Bernardo",downloadPdfUrl:"/chapter/pdf-download/53916",previewPdfUrl:"/chapter/pdf-preview/53916",authors:[{id:"191984",title:"Dr.",name:"Bernardo",surname:"Franco",slug:"bernardo-franco",fullName:"Bernardo Franco"},{id:"191985",title:"Dr.",name:"Naurú Idalia",surname:"Vargas-Maya",slug:"nauru-idalia-vargas-maya",fullName:"Naurú Idalia Vargas-Maya"}],corrections:null},{id:"54261",title:"Biosensor Platforms for Rapid Detection of E. coli Bacteria",doi:"10.5772/67392",slug:"biosensor-platforms-for-rapid-detection-of-i-e-coli-i-bacteria",totalDownloads:6928,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Risks of contamination with the well-known food pathogen Escherichia coli are increasing over the years. Therefore, rapid and portable technologies using different types of advanced devices named biosensors with various transduction capabilities (electrochemical, optical, or acoustic) were developed and seem to offer the most elegant solutions for research communities and final users-humans. Thus, integration of microfluidic biochips/biosensors into smartphones offer the real-time detection of any infection with E. coli, helping doctors in proceeding immediately with the clinical treatment. The present chapter will discuss about the analytical performances of biosensors and microfluidics such as selection of substrates, type of (bio)functionalization, low limit of detection, specificity, and response time for monitoring different E. coli strains. Thus, it is possible to rapidly identify (30–90 s) very low concentrations of E. coli (101 CFU/mL) down to a single bacterium in real samples (water, urine, milk, beef-meat) by simple integration of an angle scatter method and microfluidic-cellulosic pads (μPAD) loaded with micro-/nanoparticles functionalized with either polyclonal anti E. coli antibodies or with DNA strains into a portable device—a smartphone. Such biosensor configuration can also be used for the detection of other types of microorganisms with potential human and animal health concerns.",signatures:"Rodica Elena Ionescu",downloadPdfUrl:"/chapter/pdf-download/54261",previewPdfUrl:"/chapter/pdf-preview/54261",authors:[{id:"190834",title:"Associate Prof.",name:"Rodica",surname:"Ionescu",slug:"rodica-ionescu",fullName:"Rodica Ionescu"}],corrections:null},{id:"54674",title:"Essential Oils: The Ultimate Solution to Antimicrobial Resistance in Escherichia coli?",doi:"10.5772/67776",slug:"essential-oils-the-ultimate-solution-to-antimicrobial-resistance-in-i-escherichia-coli-i-",totalDownloads:1416,totalCrossrefCites:7,totalDimensionsCites:13,hasAltmetrics:1,abstract:"Antimicrobial resistance (AMR) is on the rise; the only solution for overcoming this is through accelerated drug discovery. At current, bacterial evolutionary rates is still clearly the undisputed winner in this war. To circumvent this, evolution of resistance need to be curbed and this can only be effective via novel approaches, one of which includes the use of a resistance modifying agent. The criterion to qualify as a resistance modifier necessitates the co-administration of the agent with an inhibitor that deactivates the bacterial resistance mechanism, restoring its original effectiveness. Natural products such as plant extracts and essential oils (EOs) have been viewed as a privileged group for investigation of their potential roles to combat antibiotic resistance, due to their compositions of active chemical compounds. The route for multidrug resistance development in Gram‐negative bacteria is primarily mediated by the sophisticated inner and outer membrane barriers, which function to protect the cell against external toxic compounds; hence, bypass of these bacterial membranes would successfully restore or improve efficacy of the antimicrobials. The aim of this chapter is to concisely describe some examples for recent strategies used in the screening of possible resistance modifiers from essential oils specifically against MDR Escherichia coli.",signatures:"Polly Soo Xi Yap, Shun Kai Yang, Kok Song Lai and Swee Hua Erin\nLim",downloadPdfUrl:"/chapter/pdf-download/54674",previewPdfUrl:"/chapter/pdf-preview/54674",authors:[{id:"190224",title:"Dr.",name:"Swee Hua Erin",surname:"Lim",slug:"swee-hua-erin-lim",fullName:"Swee Hua Erin Lim"},{id:"195385",title:"MSc.",name:"Polly Soo Xi",surname:"Yap",slug:"polly-soo-xi-yap",fullName:"Polly Soo Xi Yap"},{id:"195386",title:"BSc.",name:"Shun Kai",surname:"Yang",slug:"shun-kai-yang",fullName:"Shun Kai Yang"},{id:"221544",title:"Dr.",name:"Kok-Song",surname:"Lai",slug:"kok-song-lai",fullName:"Kok-Song Lai"}],corrections:null},{id:"54823",title:"Horizontal Gene Transfer and the Diversity of Escherichia coli",doi:"10.5772/intechopen.68307",slug:"horizontal-gene-transfer-and-the-diversity-of-i-escherichia-coli-i-",totalDownloads:1903,totalCrossrefCites:4,totalDimensionsCites:8,hasAltmetrics:1,abstract:"Escherichia coli (E. coli) strains are normal flora of human gastrointestinal tract. The evolution encoded by horizontally-transferred genetic (HGT) elements has been perceived in several species. E. coli strains have acquired virulence potential factors by attainment of particular loci through HGT, transposons or phages. The heterogeneous nature of these strains is because of HGT through mobile genetic elements. These genetic exchanges that occur in bacteria provide the genetic diversity.",signatures:"Maryam Javadi, Saeid Bouzari and Mana Oloomi",downloadPdfUrl:"/chapter/pdf-download/54823",previewPdfUrl:"/chapter/pdf-preview/54823",authors:[{id:"141443",title:"Prof.",name:"Mana",surname:"Oloomi",slug:"mana-oloomi",fullName:"Mana Oloomi"},{id:"191998",title:"Prof.",name:"Saeid",surname:"Bouzari",slug:"saeid-bouzari",fullName:"Saeid Bouzari"},{id:"191999",title:"MSc.",name:"Maryam",surname:"Javadi",slug:"maryam-javadi",fullName:"Maryam Javadi"}],corrections:null},{id:"53934",title:"Molecular Mechanisms of Phosphate Homeostasis in Escherichia coli",doi:"10.5772/67283",slug:"molecular-mechanisms-of-phosphate-homeostasis-in-i-escherichia-coli-i-",totalDownloads:2143,totalCrossrefCites:7,totalDimensionsCites:10,hasAltmetrics:0,abstract:"Life’s processes absolutely require inorganic phosphate for structural and energetic purposes. Escherichia coli has developed sophisticated mechanisms to acquire phosphate and to maintain intracellular amounts at optimal levels. The processes by which these simple cells maintain stable intracellular concentrations of phosphate are termed phosphate homeostasis, which involves mechanisms to balance the import, assimilation, sequestration, and export of phosphate. This chapter introduces the proteins involved in phosphate homeostasis and reviews information concerning the multiple phosphate transporters and the mechanisms by which they are regulated. It also introduces new concepts of how this bacterium responds to elevated extracellular levels of phosphate and presents a model for the integration of all of these processes to achieve homeostasis. The predominant importers are PitA, PitB, and the PstSCAB complex. Assimilation, or the incorporation of Pi into organic molecules, occurs primarily through the formation of ATP. Gene regulation relies on the PhoB/PhoR two-component system and the formation of a signaling complex at the membrane. The amount of intracellular phosphate can be fine-tuned through the formation or degradation of polyphosphate. Polyphosphate formation requires adequate supplies of ATP. In addition, when intracellular phosphate levels become too high, phosphate can be exported through PitA, PitB, or the YjbB transporters.",signatures:"William R. McCleary",downloadPdfUrl:"/chapter/pdf-download/53934",previewPdfUrl:"/chapter/pdf-preview/53934",authors:[{id:"191441",title:"Dr.",name:"William",surname:"McCleary",slug:"william-mccleary",fullName:"William McCleary"}],corrections:null},{id:"54277",title:"From Biology to Biotechnology: Disulfide Bond Formation in Escherichia coli",doi:"10.5772/67393",slug:"from-biology-to-biotechnology-disulfide-bond-formation-in-i-escherichia-coli-i-",totalDownloads:1598,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Disulfide bonds formed between a pair of oxidized cysteines are important to the structural integrity and proper folding of many proteins. Accordingly, Nature has evolved several systems for the genesis and maintenance of such bonds. Beginning with the discovery of protein disulfide isomerase, which provided the first evidence for enzyme-catalyzed disulfide-bond formation, many years of research have resulted in the explication of the complex network of electron transport pathways needed for this process. Herein, we take a historical approach in describing the elucidation of disulfide-bond formation in E. coli. We frame this topic in the context of genome sequencing eras. The first section describes the discovery of eukaryotic protein disulfide isomerase and the subsequent research that followed from the early 1960s to the early 1990s, a time period we have named the pre-genomic sequencing era. The second section details the renaissance in research on disulfide-bond formation in the periplasm of prokaryotes, fueled by bacterial genetic screens and the development of genomic sequencing technology. Accordingly, we have named this section the genomic sequencing era, which ranges from the early 1990s to approximately 2010. The final section outlines the use of bacterial genetic screens to select for new oxidoreductase enzymes and their potential uses in biotechnological and pharmaceutical applications. This era we have dubbed the post-genomic sequencing era, and we envision it to represent the future of research on oxidative folding.",signatures:"Bradley J. Landgraf, Guoping Ren, Thorsten Masuch, Dana Boyd and\nMehmet Berkmen",downloadPdfUrl:"/chapter/pdf-download/54277",previewPdfUrl:"/chapter/pdf-preview/54277",authors:[{id:"190999",title:"Dr.",name:"Mehmet",surname:"Berkmen",slug:"mehmet-berkmen",fullName:"Mehmet Berkmen"}],corrections:null},{id:"54396",title:"Survival Strategy of Escherichia coli in Stationary Phase: Involvement of σE-Dependent Programmed Cell Death",doi:"10.5772/67672",slug:"survival-strategy-of-i-escherichia-coli-i-in-stationary-phase-involvement-of-e-dependent-programmed-",totalDownloads:1542,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In a natural habitat, microbes respond to alterations in the amounts of nutrients or to stresses such as osmotic stress and stresses caused by low or high pH, salt, heat, and antibiotics by changing their mode for proliferation or survival. Similarly, Escherichia coli cells in a test tube change the growth mode according to environmental conditions when they enter a stationary phase. Until a sufficient supply of nutrients, the organism survives under such stressful and nutrient-limited conditions by altering gene expression to be more protective against such conditions. The definite trigger of the onset of stationary phase is still unclear, but several lines of evidence indicate that the regulation mechanism is very complicated and involves several transcriptional factors including alternative sigma factors, σE and σS. In addition, E. coli cells behave as a community of species and give rise to programmed cell death (PCD) for ensuring survival by controlling the cell number and supplying nutrients to sibling cells in long-term stationary phase (LTSP). The main PCD is probably performed by σE in E. coli. In this chapter, physiological functions of σE and PCD are introduced and reviewed and their possible involvement in survival mechanisms in stationary phase, especially LTSP, is shown.",signatures:"Tomoyuki Kosaka, Masayuki Murata and Mamoru Yamada",downloadPdfUrl:"/chapter/pdf-download/54396",previewPdfUrl:"/chapter/pdf-preview/54396",authors:[{id:"105925",title:"Prof.",name:"Mamoru",surname:"Yamada",slug:"mamoru-yamada",fullName:"Mamoru Yamada"}],corrections:null},{id:"54626",title:"Survival of Escherichia coli under Nutrient-Deprived Conditions: Effect on Cell Envelope Subproteome",doi:"10.5772/67777",slug:"survival-of-i-escherichia-coli-i-under-nutrient-deprived-conditions-effect-on-cell-envelope-subprote",totalDownloads:1575,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In the aquatic ecosystems, microorganisms are exposed to seasonal and circadian cycles. Abiotic factors (e.g. low temperature, nutrient deprivation) can cause morphological and physiological changes in bacteria, thereby facilitating cell survival. While representing the interface between the cells and external environment, the cell envelope plays a major role in bacterial response to stress and characterization of the changes it undergoes can help to understand the adaptation process. In this study, analysis of the morphological and physiological changes as well as variations in protein composition of the Escherichia coli cell envelope was carried out for populations maintained for 21 days under nutrient deprivation and suboptimal temperatures (4°C and 20°C). It was found that the absence of nutrients led to a temperature-dependent reduction of cell culturability but had no effect on cell viability and integrity. The concentration of membrane proteins playing the key roles in cellular transport, maintenance of cell structure or bioenergetics processes remained mainly unchanged. In contrast, the level of several proteins such as the elongation factor EFTu 1, components of Bam complex or proteins implicated in chemotaxis was altered, thus indicating that cells were readily responding and adapting to stress.",signatures:"Maite Orruño, Claudia Parada, Vladimir R. Kaberdin and Inés Arana",downloadPdfUrl:"/chapter/pdf-download/54626",previewPdfUrl:"/chapter/pdf-preview/54626",authors:[{id:"190260",title:"Dr.",name:"Inés",surname:"Arana",slug:"ines-arana",fullName:"Inés Arana"},{id:"190272",title:"Dr.",name:"Maite",surname:"Orruño",slug:"maite-orruno",fullName:"Maite Orruño"},{id:"190273",title:"Dr.",name:"Claudia",surname:"Parada",slug:"claudia-parada",fullName:"Claudia Parada"},{id:"190275",title:"Dr.",name:"Vladimir",surname:"Kaberdin",slug:"vladimir-kaberdin",fullName:"Vladimir Kaberdin"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"825",title:"Current Topics in Tropical Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ef65e8eb7a2ada65f2bc939aa73009e3",slug:"current-topics-in-tropical-medicine",bookSignature:"Alfonso J. 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Mahmoud",coverURL:"https://cdn.intechopen.com/books/images_new/799.jpg",editedByType:"Edited by",editors:[{id:"92016",title:"Dr.",name:"Barakat",surname:"Mahmoud",slug:"barakat-mahmoud",fullName:"Barakat Mahmoud"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2068",title:"Understanding Tuberculosis",subtitle:"New Approaches to Fighting Against Drug Resistance",isOpenForSubmission:!1,hash:"077a11a53e4b135020092b8c1143f93c",slug:"understanding-tuberculosis-new-approaches-to-fighting-against-drug-resistance",bookSignature:"Pere-Joan Cardona",coverURL:"https://cdn.intechopen.com/books/images_new/2068.jpg",editedByType:"Edited by",editors:[{id:"78269",title:"Associate Prof.",name:"Pere-Joan",surname:"Cardona",slug:"pere-joan-cardona",fullName:"Pere-Joan Cardona"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"322",title:"Flavivirus Encephalitis",subtitle:null,isOpenForSubmission:!1,hash:"269535b3a2f21a46216f4ca6925aa8f1",slug:"flavivirus-encephalitis",bookSignature:"Daniel Růžek",coverURL:"https://cdn.intechopen.com/books/images_new/322.jpg",editedByType:"Edited by",editors:[{id:"33830",title:"Dr.",name:"Daniel",surname:"Ruzek",slug:"daniel-ruzek",fullName:"Daniel Ruzek"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3842",title:"Leishmaniasis",subtitle:"Trends in Epidemiology, Diagnosis and Treatment",isOpenForSubmission:!1,hash:"861f3ca84eede677ba6cd863093d62f8",slug:"leishmaniasis-trends-in-epidemiology-diagnosis-and-treatment",bookSignature:"David M. 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Annous and Joshua B. Gurtler",coverURL:"https://cdn.intechopen.com/books/images_new/2061.jpg",editedByType:"Edited by",editors:[{id:"101172",title:"Dr.",name:"Bassam",surname:"Annous",slug:"bassam-annous",fullName:"Bassam Annous"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"971",title:"Malaria Parasites",subtitle:null,isOpenForSubmission:!1,hash:"d7a9d672f9988a6d5b059aed14188896",slug:"malaria-parasites",bookSignature:"Omolade O. 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\r\n\tBiocomposites are biomaterials made up of matrices (resins) and natural fibres reinforcing. Natural fibre has been used as reinforcement in polymeric composites as a result of environmental concerns and the high cost of synthetic fibres. Thus, biofibers are the main constituents of biocomposites, which are made from biological sources such as natural polysaccharides (chitosan, alginate, starch, gelatine, and carrageenan), crop fibres (cotton, hemp, or flax), recycled wood, wastepaper, agricultural processing by-products, or regenerated cellulose fibre.
\r\n\r\n\tBiocomposites are gaining popularity quickly on the industrial level due to their high versatility and excellent performance. Examples of these applications are tissue engineering, drug delivery systems, restorative applications, storage devices, photocatalysts, biosensors, encapsulation of enzymes and cells, construction, energy, and packaging.
\r\n\r\n\tIn this book, we will focus on some of the applications of biocomposites based polysaccharides in immobilized enzymes, drug delivery systems, and packaging. The book will also be covering some of the methods used for the preparation and characterisation of these biocomposites including nanocomposites.
\r\n\t
The history of oxidation reduction reactions can be traced back to the early time of the human development, since the first time that the human knew the fire and used it in their daily life, especially the Copper‐Bronze age of the human development, the early time, around 4000–8000 years ago. In that era, people were benefited by the use of copper in their life; they heated copper ores and coal in an oxidation reduction reaction by which copper ores are reduced to copper metal and coal is oxidized to carbon dioxide, and besides the production of copper, the Bronze age is also known to use clay in the production of pottery. Greeks are the first to use oxidation reduction reaction as oxidizing and reducing fire conditions for pottery making; this can be summarized as firing clay in a rich or indigent atmosphere of oxygen. Clay containing iron will turn to orange‐red if fired under rich atmosphere of oxygen due to the presence of red iron oxide (higher oxidation state) or will turn to black if fired under indigent atmosphere of oxygen when black iron oxide forms (lower oxidation state). Then, the human development jumped to the Iron Age, which is around 3000–5000 years ago, when the human for the first time used iron mainly in production of knives and bayonets which were used in their daily lives and wars. A great historic jump in the oxidation reduction reactions is the use of explosives, first used by Chinese as early as 950 A.D. It was the Chinese who first developed this deadly weapon, but around the thirteenth century, the Europeans would have jumped on the technological band wagon, using it to devastate the natives of the New World during the Age of Exploration.
A modern exploration of the oxidation reduction reaction starts formally with Georg Ernst Stahl [1] in 1697 when he proposed the phlogiston theory [2], which was based on the premise that the metals often produce a calx when heated (calx is defined by Stahl as the crumbly residue left after a mineral or metal is roasted), and phlogiston is given off whenever metals or something were burned; moreover, the calxes form metals when heated with charcoal and wood, and charcoal is particularly rich in phlogiston because they leave very little ash when they are burned; however, the theory of phlogiston was not widely accepted in the scientific media. Seventy‐five years later, Antoine‐Laurent Lavoisier (1743–1794) came with solid explanation of combustion [3]. In 1772, Lavoisier discovered that when phosphorus or sulfur is burned in air, the products are acidic in nature, and the products also weigh more than the original phosphorus or sulfur, and he came to the conclusion that the elements combine with something in the air to produce acids [4], but he could not recognize what was in the air that combined with phosphorus or sulfur. In 1974, he met Joseph Priestley (the father of oxygen discovery, 1733–1804) during his visit to Paris; he told Lavoisier about the gas produced when he decomposed the compound which we now call mercury oxide. This gas supported combustion much more powerfully than normal air. Priestley believed the gas was a particularly pure version of air; he started calling it dephlogisticated air, believing its unusual properties were caused by the absence of phlogiston. In 1779, Lavoisier coined the name oxygen for the element released by decomposition of mercury oxide, and from here, explanation of certain reactions as oxidation reduction officially started [5].
Coming back to the explosive materials, the year 1964 was the year that explosives, nitrocellulose and nitroglycerin, were both discovered, and later on trinitrotoluene (TNT), involved in weapon production and widely used in the First World War (1914–1919). The cheap mixture of ammonium nitrate and fuel oil was recognized as a powerful explosive in 1955, and this was used to bomb the Federal Building in Oklahoma City in 1995; finally, the explosives that were used in the fireworks are believed to be used for the first time in China in the sixth century.
Now, the five main types of redox reactions are combinations, decompositions, displacements, combustions, and disproportionations. In combination redox reactions, two elements are combined whereas one element becomes oxidant and the other reluctant; in decomposition redox reactions, a compound is broken down into its constituent parts; in displacement redox reactions, one or more atoms is swapped out for another; in combustion reactions, a compound reacts with oxygen to produce carbon dioxide, water, and heat; and in disproportionation redox reactions, a molecule is both reduced and oxidized. These types of reactions are rare, and many reactions are considered in the interface between these areas.
Concluding this historical background that chemists worldwide later recognized that other elements reacted in the same general manner as oxygen, the concepts of oxidation and reduction were extended to include other elements; electrochemistry as a new field is further broadening the definition of the oxidation reduction reaction. Investigators observed that the ferric ions could be formed from the ferrous ions by the action of oxygen gas. This consumption of oxygen, oxidation, involved a loss of electrons by the ferrous ions species, and hence, an oxidation reaction could refer also to a transfer of electrons.
An understanding of the redox reactions of inorganic and organic compounds is central to understanding the metabolism of living things. One of the most important processes that occurs in living organisms is photosynthesis, which consists of a series of oxidation reduction reactions; the series begins when the chlorophyll in barks or leaves of plant cells absorbs sunlight with certain wavelengths and converts carbon dioxide into carbon and oxygen in a reduction process and ends the series with the production of glucose molecules. In other organisms, glucose is being consumed to generate energy in a long series of enzyme‐catalyzed reactions; in simple words, electrons can be transferred from glucose to molecular oxygen, oxidizing the carbon molecules to carbon dioxide and reducing O2 to water.
This aspect of redox reactions in living organisms is called cellular respiration by which cells break down molecules of food (glucose) in a series of chemical reactions to produce energy, carbon dioxide, and water; the process depends heavily on the reduction of NAD+ to NADH and the reverse oxidation reaction of NADH to NAD+ as intermediate steps [6]. The oxidation of glucose is a thermodynamically favored process, meaning the transfer of electrons from glucose to O2 is thermodynamically downhill, and cells use this released energy to carry out a wide variety of energy‐requiring activities. Figure 1 illustrates how glucose is burned in a series of redox reactions and ends up in the formation of carbon dioxide and energy that is stored as adenosine triphosphate (ATP); in the diagram called Krebs Cycle which describes cell burning of glucose, enzymes are used in each step to lower the activation energy for each step and aid in breaking and formation of bonds; the overall reaction is a redox reaction, that is, electrons are lost or gained in each step.
An illustrated diagram for Krebs cycle, copied from the website, https://wikispaces.psu.edu.
Other biological processes that involve the redox reaction is the production of free radicals, which can be produced by detaching electrons from certain type of molecules and reattaching to another type of molecule instantaneously; free radicals play an important role for the programmed cell death (apoptosis), and any uncontrolled production of free radicals may lead to cause cancer [7].
Corrosion is another type of redox reaction; it occurs when a metal comes in contact to a solution or at least moisture; the metal corrodes with evolving of electrons that move to cathodic part of the so‐called localized galvanic cell, and then, cathodic reaction starts with the production of hydrogen gas if the electrolyte is acidic or conversion of water to hydroxide if the electrolyte is neutral or basic. In this case, the intensity of flow of electrons from the anodic part (metal) to cathodic part (electrolyte) is defined as the corrosion current; there may be some microscopic galvanic cells with adjacent distance or some distance apart if the electric current in the galvanic cells is huge and is more than the electrolyte capacity to allow the current to pass, then the operation is governed by the movement of electrolyte ions; on the other hand, if the electric current is less than the electrolyte capacity to allow the current to pass, then the operation is governed by activation energy. One of the famous corrosion examples is the iron rust, and in this case, iron is oxidized at the beginning to ferrous ions releasing two electrons, and the reaction will proceed as long as the metal is capable of releasing electrons and electrolytic solution to carry the ions; the corrosion current is increased by increasing the number of oxidized iron atoms, and if there is excess of oxygen in electrolyte, then ferrous ions are oxidized further to ferric ions that can give ferric oxide or ferric carbonate which is the main constituent of the iron rust. Besides iron, most of elements in the periodic table are capable to corrode, and corrosion now has become a global problem that should be controlled if it could not be stopped (according to the second law of thermodynamics); the biggest breakthrough that has been achieved in the corrosion research is the invention of the electrochemical series, a series in which ordering the periodic table elements depends on the redox potential, and the most benefit of this is trying not to gather two elements of far different reduction potential in one alloy because that is produced in fast corrosion.
To start a discussion on this, let us first ask this question, is the combustion reactions is a redox reaction? Answering this, as the oxidation state is changed from 0 in the molecular oxygen to −2 in the species that produce in the reaction, the reaction is a redox in nature; combustion in the form of fire produces flame and a considerable amount of heat, which can make combustion self‐sustaining. In case of burning metals such as mercury, copper, zinc, and so on, the product is the metal oxide; in case of burning organic molecules, the products are carbon dioxide, water, and heat, and the combustion reaction is not as easy as it looks; probably the reaction takes place in a series of more than 10 steps, and hence finding the overall rate of reaction becomes extremely complicated, and the computer softwares are the only logical solution for this. MatLab, Avogadro, Copasi, and Kintecus are some of the most powerful softwares used in this regard.
Potassium nitrate, when mixed with carbon and sulfur in correct ratios which are the constituents of gunpowder, nitrate is reduced to form nitrogen, mono and dioxides, while carbon is oxidized to form carbon mono and dioxides, and sulfur is oxidized to form di and trioxides. The reaction will not start unless it is initiated; it has been found that such reactions can be initiated by electric shocks, spark, or electric current, and the reaction is maintained in a series of complicated steps; production of all these gases increase suddenly the pressure, the contents of the reaction come to explode to relieve the pressure, and besides increase in pressure, temperature is also increased tremendously; the main mechanism of explosive reaction is the chain reaction by which one product of the reaction, called free radical, is initiated and activates other molecules in the reaction mixture, and the reaction is proceeded till all free radicals are used up.
Although nuclear explosion is one of the massive explosions on earth, but is not itself a redox reaction, and is something more complicated, as in the case of uranium, the nuclei split and form two different elements and release energy more than any ordinary explosive.
Nowadays, redox reactions fuel the most advanced form of the space transportation and the space shuttle; powdered aluminum and ammonium perchlorate are used to undergo redox reactions that produce the gases hydrogen and oxygen and give the shuttle enormous amount of extra thrust; the redox reaction is represented as follows:
It produces temperatures of about 5700 F and 3.3 million pounds of thrust in each rocket; thus, the redox reactions furnish the energy to launch the space shuttle.
Besides the above examples, so many examples can be drawn to prove the importance of applications of redox reactions in general life; in electrochemical cells, electrons formed from the oxidation of one element and pass through a conductor to the reduction element; bleaching solutions that are used to brightening clothes are made of oxidizing agent (clorox), and this oxidizes any constituent that is capable of being oxidized and then make clothes clean and bright, and so on.
In this summarized introduction, we aimed to draw the reader’s attention to the wide range of applications as well as the importance of redox reactions; luckily, chapters of this book can be categorized into two main parts: Part (1) batteries and computer applications and part (2) drugs and biological applications, and the diverse of chapters exhibit clearly the wide range of researches in the field of redox reactions.
Biomedical application of nanotechnology has revolutionized tissue engineering as it can generate efficient biocompatible scaffolds with tuneable physico-chemical properties. Controllable biodegradability is one of the most important aspects as it supports the cells to produce extracellular matrix and promote effective healing. Likewise, adjustable pore structures of the scaffolds provides attractive site for loading drugs for resisting post-surgical infections and promoting cell attachment and colonization. Excellent biomechanical properties obtained by rational selection of the bioink help to mimic the tissue microenvironment and provide load bearing capacity to the tissue after repair [1]. Adherence of cells, proliferation and induction of osteogenic differentiation is higher when the total porosity of the 3D printed surfaces are more than 90% [2, 3]. Hence, such scaffolds with architectural specificity to the desired tissue like bone, cartilage, heart or nerves is immensely critical during implantation in order to ensure regeneration of the new tissue followed by repair [4].
Complete healing in traumatic injury is often a challenge that requires complicated surgical procedures which are often associated with failures and post-surgical infections. Till date bone grafting using autografts, allografts, xenografts, and synthetic bone grafts are employed for fixing the injury [5, 6]. However, the factors critical for success of grafting are the optimal size, shape, biomaterial and the anatomical structure of the bone defects. Thus, 3D printed scaffolds or synthetic bone grafts are considered more feasible due to their tuneable mechanical properties identical to the original bone tissue, and ease of rapid re-vascularization [7].
Weakening and gradual damage to cartilage may also lead to joint injury. Likewise, sudden traumatic injury, formation of lesions and developmental defects may also result is degradation of cartilage and impairment of its function [8]. In the United States alone, it is estimated that around 200,000–300,000 patients have undergone cartilage surgery [9]. It is important to note that the articular cartilage is non-neural, lymphatic, and avascular, having very low self-regenerating capacity [10]. Hence 3D printing mediated fabrication of scaffolds for repair or replacement is thought to be one of the most preferable technologies for cartilage tissue engineering [11]. Similarly, in treating cardiac dysfunctions, it is essential to maintain and mimic the cardiovascular anatomy while fixing the heart defects using tissue engineered vascular grafts (TEVGs). The 3D printing has tremendously helped to fabricate patient- and operation-specific vascular grafts [12]. Further, growing cases of neurodegenerative diseases also require effective therapeutic interventions, which are ideal for axonal regeneration and functional recovery for brain and spinal cord injury (SCI). Neuroregenerative scaffolds developed by 3D printing are considered as innovative materials that mainly focus on providing supportive substrates to guide axons and break the physical and chemical barriers, thereby promoting healing [13].
Collagen type 1 is most favorable for microextrusion based 3D bioprinting of biodegradable and biosorbable scaffolds. Collagen type 1 is the most predominant protein in the extracellular and intercellular matrix, constituting 20–30% of the vertebrate connective tissue, alongside hyaluronic acid (HA). Most importantly, the biocompatibility and low antigenicity of the collagen is attributed to the repeating motifs formed by the alpha chain of hydroxyproline-proline-glycine [14]. Collagen provides highly porous structure and hence permeability which in turn facilitates adhesion, migration, differentiation in addition to the regulation of the cellular morphology [15, 16].
This chapter highlights the collagen based 3D printed scaffolds with their attractive properties such as hydrophilicity, biodegradability, permeability, plasticity and biocompatibility critical for tissue engineering.
Biomaterials composed of collagen as listed in Table 1 are considered ideal substrate for 3D printing mediated fabrication of scaffolds for tissue engineering purposes [32]. However, simulation of the tissue microenvironment is crucial to mimic the physical and morphological properties of the native tissues in order to ensure proper restoration and replacement. The following section elaborates various advances of 3D bioprinting with collagen for tissue engineering.
Tissue | Biomaterials | Reference | |
---|---|---|---|
Bone | polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP), atelocollagen | circular calvarial defects in male Sprague–Dawley rats | [17] |
Bone | calcium phosphate, Phosphoric acid, collagen | critically sized murine femoral defect | [18] |
Bone | Bioglass 45S5 (BG), methacrylated collagen (CMA) | human mesenchymal stem cells | [19] |
Bone | mesoporous bioactive glass (BG) microspheres with 4% molar percentage of strontium, Type I collagen | simulated body fluid (SBF) | [20] |
Bone | rod-like nano-hydroxyapatite particles embedded in a type I collagen matrix | — | [21] |
Cartilage | collagen, oligomeric proanthocyanidin, oxidized hyaluronic acid | rat bone marrow mesenchymal stem cells (rBMSCs), bone defects in skulls of the Sprague Dawley (SD) rat | [22] |
Cartilage | methacrylated gelatin (GelMA), nanohydroxyapatite (nHA) | bone marrow mesenchymal stem cells (BMSCs), rabbit osteochondral defect | [23] |
Cartilage | crude collagen extracted from tendons of skeletally mature rat tails | primary meniscal fibrochondrocytes | [24] |
Heart valve | gelatin support gel 3D printed with Lifeink® 200 | subcutaneous implantation in Sprague–Dawley rats | [25] |
Neonatal scale human heart | gelated collagen | human stem cell– derived cardiomyocytes | [12] |
Cardiac tissue | gelatin, gum arabic microparticles, rat collagen-I | human induced pluripotent stem cells (hiPSC)-cardiomyocytes | [26] |
Nerve | collagen, silk fibroin | neural stem cells (NSCs), spinal cord injury (SCI) in Sprague–Dawley rats | [27] |
Peripheral nerve | poly-lactic acid (PLA), collagen | PC-12 cells, Schwann cells, and primary chick dorsal root ganglia | [28] |
Elastic nerve guidance conduits (NGCs) | poly(lactide- | sciatic nerve injury models in rats | [29] |
Neural tissue | VEGF-releasing fibrin gel, Type I collagen | C17.2 cells | [30] |
Axon | chitosan, collagen | spinal cord injury (SCI) in rats | [31] |
Spinal cord | heparin sulfate, collagen | neural stem cells (NSCs) from embryonic day 14 (E14) brains, spinal cord injury (SCI) in rats | [13] |
Collagen based biomaterials for 3D printed tissues.
Collagen based scaffolds are widely used for bone tissue engineering. Hwang et al. (2017) fabricated bone grafts employing 3D printing using a composite of polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) mixed in a ratio of 4:4:2 [17]. Figure 1 shows the scanning electron microscope (SEM) images of the bone grafts. The bone graft developed by solid freeform fabrication (SFF) technique were further mixed with 3% atelocollagen and poured into a mold and incubated at 37°C for 15 min followed by deep freezing for 6 h and freeze drying for 12 h. The collagen based biomaterial was then immersed in ethanol/water (90% v/v) co-solvent containing 50 mM of 1-ethyl-3-(3-dimethyaminopropyl) carbodiimide (EDC) and 20 mM of N-hydroxysuccinimide (NHS) for 24 h at room temperature for effective cross-linking. Each cross-linked collagen block had a diameter and height of 8 mm and 2 mm, respectively. Circular calvarial defects of 8 mm diameter were created by removal of periosteum in male Sprague–Dawley rats. The PCL/PLGA/β-TCP composite block bone grafts were implanted into the defect cites. Interestingly the bone grafts were surrounded by fibrous connective tissues. Subtle bone formation was noted while infiltration of the giant cell and inflammatory cells were seen. However, after eight weeks both neovascularization and new bone formation were noted around the bone grafts. It was speculated that these novel PCL/PLGA/β-TCP composite block bone grafts may be considered as an alternative to synthetic bone grafts.
SEM images of PCL/PLGA/β-TCP particulate bone grafts. (a) Well-defined PCL/PLGA/β-TCP particulate bone grafts were confirmed at a magnification of ×100; (b) rough surface of PCL/PLGA/β-TCP particulate hone grafts were observed at a magnification of ×800. Reprinted from Hwang et al. [
In another study, Inzana et al. tailored a composite scaffold using calcium phosphate and collagen for bone tissue regeneration [18]. Phosphoric acid at a concentration of 8.75 wt% was used as a binder that significantly improved the cellular viability. Tween 80 supplementation further enhanced the strength of the 3D printed scaffolds. Further, supplementation of the binder solution with 1–2 wt% collagen significantly enhanced the maximum flexural strength and cell viability. The pore size was in range from 20 to 50 μm that may significantly facilitate in-growth of the bone and reestablishment of the marrow compartment. The surface was covered by plate like crystal growth which increased the surface area significantly that is ideal for adsorption of drugs and/or proteins. On implanting the 3D printed scaffolds into a critically sized murine femoral defect for 9 weeks, promising osteoconductive properties were noticed.
Kajave et al. (2021) developed a bioactive ink composed of Bioglass 45S5 (BG) and methacrylated collagen (CMA) for 3D printing of biomimetic constructs for bone tissue engineering [19]. The bioink resembled native bone tissue in the organic and inorganic composition. Superior stability with minimum swelling of the collagen based hydrogel was achieved due to homogeneous dispersion of BG particles within the collagen network. Excellent rheological property was confirmed by the betterment in the yield stress. Similarly, incorporation of the BG resulted in improvement in the percent recovery of 3D printed constructs. Additionally, improved bone bioactivity of 3D printed constructs in stimulated body fluid was advantageous. Osteogenic induction and differentiation by BG incorporated CMA (BG-CMA) constructs was associated with high cell viability and enhanced alkaline phosphatase activity and calcium deposition in human mesenchymal stem cells.
In another interesting study, Montalbano et al. fabricated a hybrid bioactive material suitable for 3D printing of scaffolds mimicking the natural composition and structure of healthy bone [20]. Initially mesoporous bioactive glass (BG) microspheres with 4% molar percentage of strontium were synthesized. Thereafter, Type I collagen and strontium-containing mesoporous BG were combined to obtain suspensions able to perform a sol–gel transition under physiological conditions. The fibrous nanostructures were homogeneously distributed embedding inorganic particles as evident from the field emission scanning electron microscopy (FESEM). Large calcium phosphate deposition was observed while release of strontium ions from the embedded BG was attributed to the high-water content of the composite. These features can cumulatively promote the osteogenic induction which is significant for bone tissue engineering. On soaking the composite scaffolds in simulated body fluid (SBF), hydroxyapatite (HA) crystals were uniformly distributed along the cross section of the sample that increased with time from 3rd to 7th day as evident from Figure 2.
Cross-sectional FESEM images showing HA crystal deposition on collagen/MBG_Sr4% samples after three and seven days of incubation in SBF at different magnifications. Reprinted from Montalbano et al. [
In subsequent study Montalbano et al. reported composite biomimetics comprised of rod-like nano-hydroxyapatite particles embedded in a type I collagen matrix [21]. This composite was developed to mimic the bone composition. Initially a hydrothermal method using 0.2% ammonium-based dispersing agent (Darvan 821-A) was employed for the fabrication of the HA nanorods that were uniform-sized with length of 40–60 nm and a width of 20 nm. On suspending this material in a collagen solution in presence of Darvan 821-A, a uniform collagen/nano-HA suspension was obtained that was ideal for extrusion 3D printing. The mesh-like structures printed in a gelatine-supporting bath led to fabrication of 3D bone-like scaffolds.
One of the most prevalent tissue damages suffered by adults, children and adolescents is articular cartilage defects. In severe cases degenerative joint diseases may result due to exposure of bone terminals caused by progressive wear and tear of articular cartilage. However, low rate of tissue regeneration and self-repairing capacity poses a challenge for effective healing and restoration of the function. Several collagen based 3D scaffolds are being developed for inducing cartilage regeneration that is discussed in detail in this section. Recently, Lee et al. fabricated a highly biocompatible collagen/oligomeric proanthocyanidin/oxidized hyaluronic acid (C/OPC/OHA) composite scaffold with superior compressive strengths between 0.25–0.55 MPa [22]. The composite scaffolds were 3D printed using four types of needles, 25G red plastic, 22G blue plastic, 25G red metal, and 22G blue metal to achieve 20%, 25%, and 30% porosities when pressure of 25, 15, 125, and 100 kPa were applied, respectively as illustrated in Figure 3. Porous nature of the scaffolds is advantageous for promoting both angiogenesis and cartilage ossification. The minimum and maximum storage moduli of the hydrogel were approximately 2.6 kPa and 4.1 kPa, respectively. Interestingly, an increased degradation rate of the composites was 26.6%, 30%, and 30.7% for 0, 5, and 10 mg/mL of OHA, respectively after 49 days. Higher apatite deposition on the scaffold surface was evident on day 21 on immersion in simulated body fluid. Superior cell viability (up to 90%) was achieved when rat bone marrow mesenchymal stem cells (rBMSCs) were grown on the composite scaffolds. On implantation of the scaffolds into bone defects in skulls of the Sprague Dawley (SD) rat, angiogenesis and new bone formation was evident that indicated 3D collagen-based scaffolds could be used as potential candidates for articular cartilage repair.
Optimization of 3D bioprinting parameters for obtaining porosity at 20%, 25%, and 30% using different needle densities (25G red plastic and metal, 22G blue plastic and metal) and different pressures (25, 15, 135, and 100 kPa). Reprinted from Lee et al. [
Liu et al. developed a tri-layered scaffold employing extrusion-based multi-nozzle 3D printing technology where the bioink was comprised of 15% methacrylated gelatin (GelMA) hydrogel for cartilage on top layer, a combination of 20% GelMA and 3% nanohydroxyapatite (nHA) (20/3% GelMA/nHA) hydrogel for interfacial layer, and a 30/3% GelMA/nHA hydrogel for subchondral bone at bottom layer [23]. The composite was biodegradable with maximum degradation (61.4%) in 14 days. Interconnected microtubule-like structure of each layer with interconnected spherical pores with a size of about 300 μm was observed. The Young’s modulus increased with the increase in GelMA concentration in the scaffold. The scaffolds were biocompatible with the bone marrow mesenchymal stem cells (BMSCs) while they exhibited effecting healing of rabbit osteochondral defect. Higher cartilage-specific extracellular matrix formation and collagen type II were observed on treatment with the tri-layered scaffolds. Further, effective new tissue formation and even integration with the surrounding tissues indicated their promises for repair of damages in subchondral bone by inducing cartilage regeneration.
In an interesting study, Rhee et al. fabricated 3D printing assisted soft tissue implants with high-density collagen hydrogels as illustrated in Figure 4 [24]. External heating and collagen concentrations of 12.5, 15, and 17.5 mg/mL enhanced the shape fidelity. At the highest printable concentration, the modulus of printed gel was ̴ 30 kPa. Cell viability within the tissue constructs was high and no notable decrease was observed even after 10 days of culturing. Higher infiltration of the fibochondrocytes cells throughout the collagen matrix was found by 10 days. Adherence of the cells on the outer surface of the nascent collagen fibers was prominent while very few cells colonized the spaces between the fibers.
Printing process of sheep meniscus, (a) CT scan of meniscus, (b) print path of meniscus deposition of collagen hydrogel during printing, (c) 3D printed meniscus. (d) Geometry assessment of constructs. (e) Constructs scanned using Cyberware 3D scanner. (f) Geometry of the test construct: Half-cylinder. Reprinted with permission from Rhee et al. [
Cardio-vascular defects such as aortic valve disease (AVD) require high precision surgical procedure that include either mechanical or bioprosthetic valve replacement. Recently, tissue engineered heart valves (TEHV) have gained more attention that are effectively achieved by 3D bioprinting. Maxson et al. evaluated the recellularization potential of 3D-bioprinted scaffold and investigated its applicability as a heart valve implant [25]. Allogenic rat mesenchymal stem cells (rMSCs) with green fluorescent protein (GFP) label were grown and mixed with Lifeink® 200 to obtain a homogenous bioink. Thereafter, a computer aided design (CAD) model for the implant disk scaffolds was prepared wherein the dimensions of the scaffold facilitated easy implantation and mounting in order to avoid migration and folding. Neovascularization was observed after 4 weeks with integration of host tissues with the bioink explants. Moreover after 8 weeks, minimal difference between the two layers was observed; however, the structural integrity of the extracellular matrix (ECM) was maintained. Furthermore, Mason’s trichome revealed fibrosis on the cutaneous side of the explant whereas CD3 and CD163 biomarkers demonstrated chronic inflammation as well as ECM remodeling whose expressions were decreased with subsequent increase in incubation period. CD163 displayed a steady reduction in expression from week 1 to week 8, respectively. On the other hand, CD31 biomarker expression was considerably increased within the same time period due to endothelialization and angiogenesis. The vimentin (a major intermediate filament of smooth muscle cells) concentration of surrounding tissues was also increased with improvement in elastin concentration. This was attributed to the infiltration of the Bioink by interstitial-like cells. In addition, the ultimate tensile strength (UTS) was decreased from 0.344 ± 0.120 MPa in the second week to 0.169 ± 0.077 MPa in the fourth week while it was increased to 0.275 ± 0.166 MPa in the eighth week. Likewise, the tensile modulus was also reduced from 1.186 ± 0.872 MPa in the second week to 0.548 ± 0.341 MPa in the fourth week followed by an increase to 1.425 ± 0.620 MPa in the eighth week. Elastin concentration was significantly increased in the fourth week. Post eight weeks of implantation, expression of CD31 biomarker continued to decrease while CD163 expression increased in week 12 which was attributed to M2 macrophage infiltration. Additionally, the bioink explant was encapsulated by the fibrotic tissue within week 12 while UTS was further increased within this time period. Enhanced levels of both vimentin and elastin indicated strengthening of the extracellular matrix in the bioprinted scaffold due to active collagen deposition. Hence, collagen-based bioink application was demonstrated to be efficient for formation of heart valves.
In another study, Lee et al. also demonstrated 3D bioprinting of collagen for human heart engineering [12]. Herein, 3D bioprinting was carried out using a second generation of the free form reversible embedding of suspended hydrogels (FRESH v2.0) that provides support for printing and then subsequently melts away at 37°C. Moreover, uniform gelatin microparticles with spherical morphology (with diameter ̴ 25 μm) reduced polydispersity. An optimal balance between the resolution of individual strand and strand-to-strand adhesion was further maintained using a 50 mM N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES) buffered bath with pH 7.4 which in turn facilitated multiple bioink printing. A linear small coronary artery-scale tube was then fabricated using collagen type I perfusion system with an inner diameter and wall thickness of 1.4 mm and 300 μm, respectively. Thereafter, C2C12 cells were perfused in the tube that displayed viability along with active remodeling of the gel after five days. Further, cellular infiltration was also analyzed using fabrication of collagen disks with a thickness of 5 mm and a diameter of 10 mm wherein excessive cellular infiltration as well as collagen remodeling was observed post three days of implantation in the printed collagen as compared to solid-cast collagen. Moreover, fibronectin and vascular endothelial growth factor (VEGF) were incorporated into the bioink for enhanced vascularization. An extensive vascular network was observed in the printed collagen disk with red blood cells and CD31-positive vessels having a diameter range of 8–50 μm. Thereafter, collagen bioink was used along with human stem cell-derived cardiomyocytes to FRESH print a left ventricle model wherein around 96% post-printing cell viability was achieved through rapid collagen neutralization. A dense layer of interconnected and striated human embryonic stem cell-cardiomyocytes (hESC-CMs) was obtained after seven days of culturing. A baseline spontaneous ventricle beat rate of around 0.5 Hz was captured that was paced at 1 and 2 Hz using field stimulation. Furthermore, the mechanical integrity of the constructs was demonstrated using a 28 mm tri-leaflet heart valve that was robust enough to withstand air pressure. In addition, a neonatal-scale human heart was also printed using collagen bioink that highlighted the potential of FRESH v2.0 printing technique for fabrication of advanced tissue scaffolds for other organ systems as well.
Collagen-based bio-ink was also demonstrated to be an effective tool for direct 3D printing of human induced pluripotent stem cells (hiPSC)-cardiomyocytes that could then be utilized for cardiac tissue engineering [26]. Cardiomyocytes were differentiated in a 2D monolayer followed by CHIR99021-treatment mediated cell expansion and regular passing. Later on, a rat collagen-I based bioink was used for the encapsulation of cells followed by printing in a support bath composed of complex coacervate gelatin/gum arabic microparticles. The bioink was then gelated at 37°C and cultivated under free-floating conditions for a time period of thirty days. Ring-shaped cardiac tissues were printed with 5 × 5 × 1 mm dimension wherein the initial contractions were seen post three days of culturing. Striated sarcomeres were demonstrated with significant responsiveness toward pharmacological stimulations. Therefore, this study demonstrated potential of cardiac tissue engineering with enhanced properties and functions through 3D-bioprinting.
Scaffolds rationally fabricated employing 3D bioprinting could help in the treatment of spinal cord injury (SCI) by nerve tissue engineering. In a study by Jiang et al., Collagen/silk fibroin scaffold was 3D bioprinted and combined with neural stem cells (NSCs) to promote nerve regeneration [27]. A collagen/silk fibroin ratio of 4:2 was used for scaffold preparation using a 3D-bioprinter with a nozzle diameter of 210 μm, printing speed of 9 mm, extrusion speed of 2-mm/min, 0.1 mm thickness and a platform temperature of −20°C. Characterization of the 3D bioprinted scaffolds in rats revealed complete degradation of the composite scaffold after 4 weeks of implantation. Furthermore, the scaffold had considerable ductility as well as compression resistance with a compressive elastic modulus of 60.05 ± 5.12 kPa. Fourier transform infrared (FTIR) spectroscopy results then revealed presence of absorption peaks at 3445.7, 2932.46, 1640.58, and 1376.45 cm−1 that corresponded with -OH or -NH peak, methyl or C-H stretching vibrations of methylene group, C=O or C=C stretching vibrations, and saturated C-H bending vibration, respectively. Hence, these functional groups suggested presence of suitable lipid- and water-soluble bonds in the 3D bioprinted scaffold that may facilitate adhesion and growth of nerve cells. Moreover, significant biocompatibility between the scaffold and NSCs were attained with evenly distributed micropores and pore connections in the scaffold as observed in scanning electron microscopy (SEM) images. Fusiform-shaped cells grew in the scaffold pores, while some cells grew densely on the scaffold surface with extended pseudopods facilitating cell adhesion, growth as well as provided a carrier and channel for regeneration of the nerve fibers. Hence, a conducive microenvironment for NSC adhesion, growth and differentiation was provided by the 3D-bioprinted scaffold. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay also demonstrated successful seeding and proliferation of the NSCs on the scaffold. Thereafter, behavioral changes at the spinal cord injury site were investigated after implantation of the scaffold. The Basso-Beattie-Bresnahan (BBB) open-field locomotor score of the group implanted with 3D-collagen/silk fibroin scaffolds and NSCs was higher as compared to the control after 8 weeks of surgery. In addition, motor function recovery was better in groups having the scaffold and NSCs. Similarly, electrophysiological studies revealed prominent recovery in groups having 3D bioprinted scaffold along with NSCs as compared to control groups. Left hind limb amplitude was significantly higher in scaffold group when compared with control after 1 month of surgery. In addition, magnetic resonance imaging (MRI) and diffusion tensor imaging revealed improved filling of the injury cavity, enhanced spinal cord continuity, increased regenerative axons as well as reduced glial scarring in groups implanted with the scaffold and NSCs.
In another study, Li and Gao fabricated 3D microtubular collagen scaffolds and investigated its potential in peripheral nerve repair [28]. Melt spinning or 3D printing using poly-lactic acid (PLA) was carried out to obtain fibrous template material with a diameter range of 50–100 μm that was then utilized for fabrication of collagen scaffolds. Microtubules were prepared by parallel stacking of melt spun PLA fibers followed by polymerization of the collagen whereas PLA fibers with a diameter of 200 μm and 100 μm interspacing was fused and deposited using 3D printing. The thickness of inner ranged from 10 to 20 μm while the exterior wall formed a shell with a thickness of about 70 μm. Furthermore, cell adhesion ability of adrenal phaeochromocytoma (PC-12) and D62PT Schwann cells was evaluated wherein the cells firmly attached to native as well as chloroform-exposed Matrigel films. Two crosslinkers namely, 0.3% genipin and 0.3% glutaraldehyde were used that decreased swelling as well as enzymatic degradation of the Matrigel. Untreated gels demonstrated retention of 34.5% of total mass after 24 h incubation with 0.05% collagenase, whereas genipin and glutaraldehyde treated gels showed total mass retention of 96.7% and 99.3%, respectively. PC-12 and D62PT Schwann cells further showed well adherence and confluent growth onto microtubule scaffolds after 10 and 4–5 days of culturing, respectively. Moreover, a strong alignment of cells as well as formation of channels was seen in Schwann cells while primary chick dorsal root ganglia displayed neurite growth along the major axis of the microtubes.
Likewise, Yoo et al. reported fabrication of elastic nerve guidance conduits (NGCs) using poly(lactide-
Lee et al. also demonstrated bio-printing of collagen and VEGF-releasing fibrin gel scaffolds and investigated its potential in artificial neural tissue construction [30]. Murine neural stem cells (NSCs) were cultured in Dulbecco’s modified Eagle’s medium (DMEM) and further used for cell printing. Type I collagen was then prepared and 1.16 mg/mL of the collagen scaffold was used for 3D bio-printing of C17.2 cell-scaffold complex. An average of 56 ± 9 cells/droplet was obtained with a cell viability of 93.23 ± 3.77% which was similar to that of manually-plated cells. Moreover, a collagen scaffold concentration of 1.74 mg/mL demonstrated highly dense and proliferating cells with a viability of 96.72 ± 3.58% after 3 days of culturing. Furthermore, the combinatorial effect of collagen scaffold and VEGF-containing fibrin gel on C17.2 cells was investigated wherein, the cell morphology altered after two days of culturing with active proliferation and formation of clusters. In addition, the cells located near the fibrin gel border gradually migrated toward the VEGF-containing fibrin gel and continued differentiation. After three days of culturing, the total migration distance was 102.4 ± 76.1 μm. Hence, proper cell proliferation and migration was displayed using the two scaffolds which highlighted the potential of 3D bioprinting in artificial tissue construction.
Likewise, axon regeneration was ameliorated by Sun et al. using 3D printed collagen/chitosan scaffolds [31]. A 3D bioprinter was used for fabrication of the scaffold that had an interconnected porous structure with a porosity of 83.5% as observed in SEM images. The pore size of the scaffold ranged from 60 to 200 μm. Hence, significant space was obtained by the cells for growth and adherence. The compressive modulus of 3D collagen/chitosan scaffold was 3.82 ± 0.25 MPa along with enhanced compressive strength of 345.20 ± 29.60 KPa. The cytocompatibility of 3D printed scaffolds was similar to that of scaffolds prepared using freeze drying technology. Interestingly, the persistent locomotion recovery as well as significant increase in blood brain barrier (BBB) scores was observed after implantation of the 3D printed collagen/chitosan scaffolds in rats with spinal cord injury (SCI). Moreover, the magnetic resonance and diffusion tensor imaging results revealed a significant signal increase at the epicenter of the spinal cord lesion in rats implanted with 3D printed collagen/chitosan scaffold. Post eight weeks of SCI surgery, the axonal regeneration was demonstrated wherein 3D collagen/chitosan implantations resulted in amplitude and latency improvement. Further confirmation of axonal regeneration was carried out using anterograde biotin dextran amine (BDA) labeling wherein BDA-positive fibers were observed in 3D collagen/chitosan implantations. Hematoxylin and eosin (HE) staining also demonstrated linear ordered structure of the spinal cord after eight weeks with no obvious cavity observed in 3D printed collagen/chitosan implanted group whereas visible cavities and disordered structures were observed in injury groups. Hence, 3D printed scaffolds were demonstrated to be effective in axon regeneration and amelioration of spinal cord injury.
In a similar study, Chen et al. constructed collagen/heparin sulfate based scaffolds using 3D bioprinting and evaluated its action in functional SCI recovery in rats [13]. The scaffold was prepared using a 3D bioprinter that had a cylindrical morphology with a uniform and regular internal structure along with high porosity as observed in SEM images. The compressive modulus of 3D printed collagen/heparin sulfate was 3.46 ± 0.278 MPa which was higher as compared to scaffolds prepared using freeze drying technology. Likewise, enhanced compressive strength of 308.9 ± 28.65 KPa was observed in 3D printed scaffold. Furthermore, release profile of basic fibroblast growth factor (bFGF) from 3D printed scaffold was also evaluated wherein scaffolds prepared using freeze drying method demonstrated an initial burst of 54.89% of bFGF was released in the first day after which a slow release behavior was observed for longer time period. However, a steady bFGF release behavior was observed in case of 3D printed scaffolds for twenty days. Thereafter, the biocompatibility of scaffolds was analyzed using NSCs which proliferated inside the pore followed by spreading on the wall of the scaffolds. In addition, MTT assay revealed no significant difference in cell growth on different scaffolds thus highlighting the cytocompatibility of the 3D printed collagen/heparin sulfate scaffolds. Implantation of the 3D printed scaffolds further demonstrated significant recovery of locomotor functions in rats after two months with amelioration of the SCI as well as enhanced number of neurofilament positive cells.
Advances in the field of nanomedicine have enabled exploration of novel biomaterials for tissue engineering. Among various biopolymers such as, chitosan, alginate, silk fibrion, collagen is considered as most attractive due to its biocompatibility and biodegradability. However, high temperature and extreme conditions during fabrication and bioprinting results in low stability of the collagen molecules. Hence, ideal porous scaffolds should involve combination of type I collagen and hydroxyapatite particles by freeze-drying. It is essential to have tuneable pore dimensions for superior ingrowth of cells and blood vessels. More complex microarchitectures of the collagen based scaffolds with specific rheological properties such as shear thinning, yield stress and fast shear recovery can be obtained using extrusion-based 3D printing [33].
Various biologically synthesized nanoparticles like silver, gold, copper, platinum, palladium and others can be supplemented in the scaffolds resisting post-surgical microbial infections [34, 35, 36, 37]. Biofilm associated infections are most challenging to treat and are highly responsible for implant failure. Hence, coating of implants with antimicrobial nanoparticles impregnated collagen can be an effective strategy to increase the shelf life of the implants [38, 39]. Also drug functionalized nanoparticles can be embedded in the collagen matrix to ensure sustained release and rapid healing of the injured tissues.
Multiple approaches and integration of medical biology and material science will certainly help to revolutionize regenerative medicine by rational tissue engineering. In view of the background collagen based 3D printed scaffolds hold tremendous potential as candidate nanotherapeutics.
Dr. Sougata Ghosh acknowledges Kasetsart University, Bangkok, Thailand for Post Doctoral Fellowship and funding under Reinventing University Program (Ref. No. 6501.0207/10870 dated 9th November, 2021).
The authors declare no conflict of interest.
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She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"355660",title:"Dr.",name:"Anitha",middleName:null,surname:"Mani",slug:"anitha-mani",fullName:"Anitha Mani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"355612",title:"Dr.",name:"Janani",middleName:null,surname:"Karthikeyan",slug:"janani-karthikeyan",fullName:"Janani Karthikeyan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334400",title:"Dr.",name:"Suvetha",middleName:null,surname:"Siva",slug:"suvetha-siva",fullName:"Suvetha Siva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"334239",title:"Prof.",name:"Leung",middleName:null,surname:"Wai Keung",slug:"leung-wai-keung",fullName:"Leung Wai Keung",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Hong Kong",country:{name:"China"}}}]}},subseries:{item:{id:"95",type:"subseries",title:"Urban Planning and Environmental Management",keywords:"Circular economy, Contingency planning and response to disasters, Ecosystem services, Integrated urban water management, Nature-based solutions, Sustainable urban development, Urban green spaces",scope:"