Zühlke classification.
\r\n\tThe development of sustainable waste management strategies has become a major concern throughout the world. Therefore, the new book focuses on “recycling” and “recovery” of waste material while paving the way towards a circular economy including land reclamation, and water and wastewater treatments.
\r\n\r\n\tThe book aims to provide a platform to present research in regards to:
\r\n\t(1) Sustainable Waste Management;
\r\n\t(2) Micro(nano)plastics in the Environments;
\r\n\t(3) Electronic Waste and Circular Economy;
\r\n\t(4) Reducing, Recycling and Recovery of Agricultural and Food Waste;
\r\n\t(5) Biomass Valorization: Waste to Resources;
\r\n\t(6) Governmental Policy on Waste Management and Valorization.
\r\n\tThis book will offer a timely opportunity for knowledge exchange of sustainable management agenda for biological waste and remediation of soil, water and air in the local context, which satisfies the environmental compatibility, financial feasibility and social needs. It will deliberate on state-of-the-art treatment technologies, advanced management strategies, and political issues pertaining to recycling and recovery of organic waste.
",isbn:"978-1-80355-913-1",printIsbn:"978-1-80355-912-4",pdfIsbn:"978-1-80355-914-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"4ef7ac85e87a3131afb9b858b79aa870",bookSignature:"Associate Prof. Tao Zhang",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11256.jpg",keywords:"Waste Management, Microplastics, Nanoplastics, Electronic Waste, Agricultural Waste, Food Waste, Recycling, Recovery, Biomass, Resources, Governmental Policy, Environmental Protection",numberOfDownloads:64,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 10th 2021",dateEndSecondStepPublish:"December 8th 2021",dateEndThirdStepPublish:"February 6th 2022",dateEndFourthStepPublish:"April 27th 2022",dateEndFifthStepPublish:"June 26th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"7 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:'Dr. Zhang was a visiting scholar at Arizona State University in 2014 and at the University of Hohenheim in 2017. He is the director of the Circular Economy Committee of the Chinese Society for Environmental Sciences and Water Treatment and Recycling Committee of the Chinese Society for Environmental Sciences. He has been authorized 17 invention patents in China and has won the Chinese prize for the "Outstanding Young Scientist” in 2019.',coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"185487",title:"Associate Prof.",name:"Tao",middleName:null,surname:"Zhang",slug:"tao-zhang",fullName:"Tao Zhang",profilePictureURL:"https://mts.intechopen.com/storage/users/185487/images/system/185487.jpg",biography:"Dr. Tao Zhang is an Associate Professor and Ph.D. Supervisor at the College of Resources and Environmental Sciences, China Agricultural University, China. His academic background covers waste management, wastewater treatment, utilization of agricultural waste. He is awarded the Scientific Chinese - Outstanding Young Scientist Award, the Innovation Award for Industry-University-Research Cooperation of China, the Character Award - Invention and Entrepreneurship Award of China Association of Inventions. His H-index is 23 (Scopus) and he has published more than 50 papers in Chemical Engineering Journal, Water Research, Journal of Hazardous Materials, Green Chemistry, Renewable and Sustainable Energy Reviews, and so on. Amongst, 11 ESI Highly Cited Paper and 4 ESI Hot Paper. He has authorized more than 20 Chinese invention patents.",institutionString:"China Agricultural University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"China Agricultural University",institutionURL:null,country:{name:"China"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"7",title:"Business, Management and Economics",slug:"business-management-and-economics"}],chapters:[{id:"81303",title:"The Role of Biochar Systems in the Circular Economy: Biomass Waste Valorization and Soil Remediation",slug:"the-role-of-biochar-systems-in-the-circular-economy-biomass-waste-valorization-and-soil-remediation",totalDownloads:34,totalCrossrefCites:0,authors:[null]},{id:"82341",title:"Circular Economy - Recent Advances in Sustainable Construction Waste Management",slug:"circular-economy-recent-advances-in-sustainable-construction-waste-management",totalDownloads:15,totalCrossrefCites:0,authors:[null]},{id:"82278",title:"Use of Saline Waste from a Desalination Plant under the Principles of the Circular Economy for the Sustainable Development of Rural Communities",slug:"use-of-saline-waste-from-a-desalination-plant-under-the-principles-of-the-circular-economy-for-the-s",totalDownloads:15,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429339",firstName:"Jelena",lastName:"Vrdoljak",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/429339/images/20012_n.jpg",email:"jelena.v@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"19709",title:"Biomaterials and Biotechnology Schemes Utilizing TiO2 Nanotube Arrays",doi:"10.5772/23320",slug:"biomaterials-and-biotechnology-schemes-utilizing-tio2-nanotube-arrays",body:'Ti and Ti alloys are corrosion resistant, light, yet sufficiently strong for utilization as load-bearing and machinable orthopaedic implant materials. They are one of the few biocompatible metals which osseo-integrate, provides direct chemical or physical bonding with the adjacent bone surface without forming a fibrous tissue interface layer. For these reasons, they have been used successfully as orthopaedic and dental implants (Ratner 2004). To impart even greater bioactivity to the Ti surface and enhance integration properties, surface treatments such as surface roughening by sand blasting, formation of anatase phase TiO2 (Uchida et al. 2003), hydroxyapatite (HAp) coating, or chemical treatments (Ducheyne et al. 1986; Cooley et al. 1992) have been employed. However, these treatments are generally on the micron scale. Webster et al. (Webster et al. 2001; Webster, Siegel, and Bizios 1999) reported that it is even more advantageous to create nanostructured, in particular in the less than 100nm regime, surface designs for significantly improved bioactivity at the Ti implant interface and for enhanced cell adhesion. Since then, advances in biomaterial surface structure and design, specifically on the nanoscale, have improved tissue engineering in general. This chapter is a report on titanium dioxide (TiO2, or Titania) nanotube surface structuring for optimization of titanium (Ti) implants utilizing nanotechnology.
The main focus will be on the unique 3-D tube-shaped nanostructure of TiO2 and its effects on creating profound impacts on cell behavior. We will also shed light on the effects of changing the nanotube diameter size and optimizing the geometry for enhanced cell behavior. This work focuses on the tissue specific areas of cartilage and bone. Specifically, we will discuss how the desired cell behavior and functionality are enhanced on surfaces with TiO2 nanotube surface structuring. Here we reveal how the TiO2 surface nano-configurations are advantageous in various tissue engineering and regenerative medicine applications, for osteo-chondral, orthopedic, and osteo-progenitor implant applications discussed here and beyond. This chapter will also shed light on future applications and the direction of nanotube surface structuring.
In general, the mechanism of TiO2 nanotube formation in fluorine-ion based electrolytes is said to occur as a result of three simultaneous processes: the field assisted oxidation of Ti metal to form titanium dioxide, the field assisted dissolution of Ti metal ions in the electrolyte, and the chemical dissolution of Ti and TiO2 due to etching by fluoride ions, which is enhanced by the presence of H+ ions (Shankar et al. 2007). TiO2 nanotubes are not formed on the pure Ti surface but on the thin TiO2 oxide layer naturally present on the Ti surface. Therefore, the mechanism of TiO2 nanotubes formation is related to oxidation and dissolution kinetics. Schematic diagram of the formation of TiO2 nanotubes by anodization process is shown in Figure 1. For a description of the process displayed in Figure 1, the anodization mechanism for creating the nanotube structure is as follows:
Before anodization, a nano scale TiO2 passivation layer is on the Ti surface.
When constant voltage is applied, a pit is formed on the TiO2 layer.
As anodization time increases, the pit grows longer and larger, and then it becomes a nanopore.
Nanopores and small pits undergo continuous barrier layer formation. (e) After specific anodization time, completely developed nanotubes are formed on the Ti surface.
Schematic illustration of TiO2 nanotube formation.
Furthermore, based on the mechanism of nanotube formation, it is inherent that the nano-tubular structure formation depends on both the intensity of applied voltage and the concentration of fluorine ions in the electrolyte solution. It is well-known that by increasing the applied voltage, larger diameter nanotubes can be formed. This aspect of diameter manipulation using applied voltage will be further emphasized and the effects on cell function and fate is also discussed.
The Jin lab was the first to demonstrate that TiO2 nanotubes can significantly accelerate osteoblast (bone cell) adhesion and proliferation at the biomaterial/tissue interface and enhance bone mineral formation. The TiO2 nanotubes are formed as vertically aligned configuration, with an average diameter of ~100 nm, a height of ~300 nm, and a wall thickness of ~10 nm. According to published research (Oh S 2006), nanotube arrays on titanium surfaces induced proliferation of osteoblasts by as much as 300 – 400% compared to non-modified titanium surfaces. In other research groups studying nanoporous materials, major accomplishments have been made in the generation of geometrically defined surfaces with the fabrication of Al and Si nanostructured surfaces. There is rapidly increasing evidence that the lateral spacing of features on the nanoscale can impact and change cell behaviour (Boyen et al. 2002; Cavalcanti-Adam et al. 2006; Popat et al. 2006). Therefore, in order to optimize the lateral spacing of the TiO2 nanotube system, by changing the geometry of the nanotubes, four different pore sizes (30, 50 70, and 100nm in diameter) were created (Figure 2) for examination of cartilage chondrocyte cells, bone osteoblast cells, and osteo-progenitor mesenchymal stem cells.
Physical characterization of different size nanotube surfaces. (a) SEM micrographs of self-aligned TiO2 nanotubes with different diameters. The images show highly ordered nanotubes with four different pore sizes between 30-100nm created by controlling the voltage from 5-20V. (b) Table with the applied voltage parameter, estimated inner pore size from SEM images, average roughness (Ra) and surface contact angle measurements for Ti and 30-100nm TiO2 nanotube surfaces.
In terms of current biologically active implants, enhanced surface roughness is one of the important factors in providing the proper cues for a positive cell response to implanted materials. However, much of the research related to the effect of macro and micro-roughness on cellular responses and tissue formation are inconclusive due to the non-uniformity of macro and micro-roughness stemming from crude fabrication methods like polishing, sand blasting, chemical etching and so on. An important aspect of our nanotube system shown in the SEM images (Figure 2) is that the nano-topography can feature a more defined, reproducible and reliable roughness than micro and macro-topography for enhanced bone cell function
Furthermore, it can be assumed that the surface area on the nano-scale may be affected based on the various sizes and the surface area probably increases proportionally with increasing nanotube size. It is expected that the surface area to be 3 times higher on the 100nm diameter nanotubes compared to the 30nm diameter nanotubes, respectively. Additionally, the contact angle describing the wettability of the surface is enhanced, more hydrophilic, on the nanotube surfaces (showing contact angles between 4-11°), which can been advantageous for enhancing protein adsorption and cell adhesion.
Cells respond to the amount and area of proteins that are available for binding. In fact, cells do not see a naked material,
SEM micrographs of flat Ti and 30, 50, 70, 100nm diameter TiO2 nanotube surfaces after 2 hours of culture showing protein adsorption from media.
Artificial cartilage prepared from cultured chondrocytes offers promise as a treatment for cartilage defects (Fedewa et al. 1998), but connecting this artificial soft tissue to bone in the attempts to restore the defected cartilage is difficult. One strategy employed in this section is to develop a dually functional substrate that supports the growth and attachment of cartilage tissue on one extremity and encourages osseointegration, a direct structural and functional connection to living bone, on the other. This substrate should be an engineered interface between artificial cartilage and native bone (Zhang, Ma, and Francis 2002).
In recent studies, Ti has emerged as a candidate material in cartilage tissue formation as well. It has been demonstrated that a micrometer porous substrate of Ti-6Al-4V provided conditions that favored cartilage tissue formation by influencing cell attachment, spreading and the amount and composition of cartilaginous tissue that forms (Spiteri, Pilliar, and Kandel 2006; Bhardwaj et al. 2001; Ciolfi et al. 2003). Not only porosity, but also surface geometry and topography have been found to have positive effects on the behaviour of chondrocytes (Bhardwaj et al. 2001).
Nanoscale topographic effects have been illustrated in nanostructured poly-lactic-co-glycolic acid (PLGA)/nanophase Titania (TiO2) composites, which have elicited an enhanced chondrocyte response compared to surfaces with a conventional or micrometer topography (Savaiano and Webster 2004). We have recently reported on our hypothesis that the nanotopographical cues, from porous nanotubular structured substrates made of TiO2, already being an osseointegrating biomaterial (Bjursten 2009; Oh et al. 2006), may also be a candidate for providing an alternative way to positively influence cartilage formation and the cellular behaviour of cartilage chondrocytes.
The dimensions of the nanotubes were varied in order to determine if the size of the nanotube diameters would play a role in the chondrocyte behaviour. For this comparative chondrocyte cell culture study, a commercially pure Ti surface, without surface modification was used as a control, as it commonly used as implant material.
It is well known that chondrocytes, the primary cells of cartilage, are extremely active cells. They produce a large amount of extracellular matrix (ECM) that is critical for the mechanical properties and joint lubrication characteristics of cartilage. In the SEM micrographs in Figure 4, the nanotubes substrates appear that they are inducing a positive response from the chondrocytes because the cells begin synthesizing abundant ECM deposition and fibril organization. In the SEM observations of chondrocytes a striking difference in the production of ECM fibrils between the flat Ti without a nanostructure vs. TiO2 nanotube surfaces is revealed. Fibrils are abundant and extending from all areas of the chondrocyte cell creating a dense network of ECM on the nanotube substrates.The flat Ti most likely lacks surface structuring cues for signaling ECM fibril production and organization. One possibility is that ECM protein formation into dense fibrils on the surface may be “nano-inspired” to form on the nanotube structure because of the precise dimensions or fine scale cues of the top surface (tip of the vertical wall) of TiO2 nanotubes having a physically confined geometry which could aid in fibril formation. It was demonstrated previously that the nanotubes produced bio-active nanostructured formations of sodium titanate nanofibers directly on the top of TiO2 nanotube walls when the nanotubes were exposed to NaOH solution (Oh S 2005). ECM proteins once secreted, in this study, may also self-assemble according to the top-wall surface geometric nanocues.
In the lower panel of Figure 4, immunofluorescent images for collagen Type II (red color) are illustrated for flat Ti vs. TiO2 nanotubes. Both surfaces stained positive for collagen type II, but there was large networks of connected bundles expressed across the surface of the nanostructure.
When a morphological analysis was conducted, it was determined that nanotubes induce a more spherical chondrocyte cell shape (data not shown). Fibroblastic shaped cells were observed on the flat controls. The percentage of round shaped, spherical cells was significantly lower for chondrocytes on the polystyrene, Ti, and the smallest diameter (30nm) nanotube substrates compared to the larger diameter 50, 70, and 100nm TiO2 nanotube surfaces respectively.
Extracellular matrix (ECM) production on experimental surfaces Ti vs. TiO2 nanotubes. High magnification SEM observations of chondrocytes reveal a striking difference in the production of ECM fibrils between the flat Ti without a nanostructure vs. TiO2 nanotube surfaces. Fibrils are abundant and extending from all areas of the chondrocyte cell creating a dense network of ECM on the nanotube substrates. (b) Immunofluorescent images of collagen type II (red) ECM fibrils produced by chondrocytes on flat Ti and nanotube surfaces (100nm diameter shown in this image).
It was also determined that all diameter nanotube surfaces were significantly higher than flat Ti which probably indicates that the cell shape was influenced by the presence of the nanostructure itself. The nanotube geometry seen in Figure 2 most likely aids in preserving the chondrocyte spherical morphology because of the distinct structure of the surface. Cells may be localized atop the pores, anchored possibly at the tip of the nanotube walls and confined by the tube contour. The chondrocytes on the flat Ti seem to be spread along the surface probably because the necessary structuring cues and nanopores needed for shape confinement are absent. To further describe the chondrocyte shape phenomenon found the experimental surfaces, a schematic is shown in Figure 5.
It was formerly assumed that focal contacts should be a specific length in order to promote adhesion and that the maximum overall contact of the cell with its substrate was most favourable (Ohara and Buck 1979). Yet, more recent studies suggest that cell-flattening or spreading is not always compatible with differing cell types, particularly in the case of chondrogenesis (Solursh 1989; Benya and Shaffer 1982; Solursh 1982; Zanetti and Solursh 1984).
Chondrocyte cell adhesion and spreading schematic determined by the size of the nanotube diameter and focal attachment sites.
Thus, the type of focal adhesion and its geometry can influence the shape the cell assumes, ultimately influencing the phenotypic expression. It has been reported that the dedifferentiation of chondrocytes in culture is usually associated with changes in cell morphology, from a rounded to a spread one (Costa Martinez et al. 2008). The results reported here suggest that creating pores by fabricating nanotubes on Ti surfaces provides a more favorable environment for the retention of the rounded morphology and the prevention of chondrocyte spreading, reducing the risk of a loss of phenotype. It should be noted that although chondrocyte cells retain this type of spherical morphology in response to the nanotube pores, different cell types will differ in size, shape, function, and how they operate on the nanotube surfaces. It is well known that different cell types elicit their own unique responses to environmental cues. The chondrocyte cells with their spherical morphology are much different than mesenchymal stem cells and osteoblast cells, described in later sections, and therefore will adhere differently to the topography and form different morphologies.
Because chondrocytes are very dynamic cells that produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans, it is important to test the biochemical ECM production on the different experimental surfaces. Therefore, to further evaluate the response of BCCs for this comparative report, the glycosaminoglycan (GAG) secretion in the media was also studied and shown in Figure 6.
Naturally, aggrecan draws water into the tissue and swells against the collagen network, thereby resisting compression and allowing for proper joint movement (Muir 1995). An interesting concept worthy to note is that the up-regulation of GAG chains indicative of increased aggrecan production observed on the larger sized nanotube pores could imply that because there are increased storage volume capabilities as pore size increases it triggers a higher rate of production because the molecule retention ability of the cellular environment has been inflated.
It was determined that there was a correlation in the increased GAG secretion in the media and the reduction of fibroblastic shaped cells. Specifically, TiO2 nanotubes with diameters in the range of 50-100nm had significantly higher levels of both round, spherical shaped cells (more phenotypic) and GAG secretion over flat Ti and small 30nm TiO2 nanotube surfaces.
Glycosaminoglycan (GAG) secretion in the media.
In this study, the larger diameters (50nm-100nm) nanotubes were revealed to be most suitable for chondrocyte culture
As Ti is the well accepted orthopaedic implant material, the results obtained are very encouraging and suggest that the use of nanotube structures could up-regulate production of extracellular matrix by chondrocytes. In clinical applications the TiO2 nanotube surface can be utilized as an
Schematic illustration of TiO2 nanotubes for dual function of osseointegration and enhanced chondrocyte function and ECM production.
As mentioned earlier, while a thin TiO2 passivation layer on the Ti surface can impart improved bioactivity and better chemical bonding to the bone (Feng et al. 2003), other techniques have been developed to further enhance the bioactivity of a pure Ti surface, such as direct coating of bioactive materials like hydroxyapatite and calcium phosphate (Puleo et al. 1991; Salata 2004; Satsangi et al. 2003). However, even though these surface modified layers have good bioactivity and high surface area, they tend to delaminate at the interface between the implant and the bone due to the relatively large, micrometer-regime thickness of the coated layer on Ti (Ong et al. 1992), presumably due to the stress accumulation commonly seen in a thick coating of foreign material. This ultimately leads to implant failure. In order to overcome this problem, some plasma spray Ca-Si based ceramic coatings have been developed but still have roughness and layer thickness in the micrometer range. For the purposes of this study, the focus is on nanoscale thickness surface coatings. Therefore, developing an implant bioactive surface layer having high surface area for enhanced bonding yet thin enough, in the nanometer range per se, to minimize delamination would be desirable.
Recent reports indicate that modifying Ti surfaces with TiO2 nanotubes for orthopedic applications significantly enhances the mineral formation (Oh et al. 2005), adhesion of osteoblasts
Because orthopedic implants encounter two types of cells, osteoblast cells in bone tissue and osteo-progenitor cells also know as mesenchymal stem cells (MSCs) present in bone marrow, it is advantageous to look at the differentiation potential of orthepeadic implant surfaces in order to initiate a mature population of bone building cells for enhanced osseointegration. One key principle in terms of orthepaedic implant technologies, to initiate the differentiation of bone in the absence of chemical factors, hormones, or any other synthetic, possibly toxic chemicals traditionally used by biochemists in
Schematic illustration showing osteo-progenitor cells developing into osteoblast cells. A description of the two cell types is also portrayed in list format.
Stem cells, which have the potential to differentiate into multiple cell types, provide great promises in advances in regenerate medicine. The differentiation of stem cells into the appropriated lineages is temporal- and spatial-specific, with the surrounding microenvironment playing critical roles in governing the stem cell fate. For generation of osteoblasts, the MSCs need to be guided to selectively differentiate to osteoblasts, rather than differentiating into other types of cells. The use of nanostructures and surface topographical features have recently been shown to have positive effects on specific differentiation of mesenchymal stem cells (Dalby, Andar et al. 2008), illustrating that the surface topography alone can stimulated osteogenic differentiation.
In terms of the dimensions of the nanotubes in our osteoblast (bone cell) and mesenchymal stem cell (osteo-progenitor cell) studies, we have reported a unique variation in cell behavior even within a narrow range of nanotube diameters from 30-100nm (Brammer et al. 2009; Oh et al. 2009) and it seems that a similar trend is established for both cell types.
When cells were grown on four different diameter nanotubes, shown in Figure 2, osteoblast functionality in terms of bone forming ability, or alkaline phosphatase activity (ALP), and mesenchymal stem cell (MSC) osteogenesis (bone cell differentiation) in terms of osteogenic gene expression (osteopontin (OPN), osteocalcin (OCN), and alkaline phosphatase (ALP)) were most prominent on the large 100 nm diameter nanotubes, Figure 9 (a and b). During periods of active bone growth, ALP activity levels are elevated in osteoblast cells so it is beneficial to design an implant surface that would enhance the ALP activity to initiate the formation of new bone. As well, it is critical to design a surface that is capable of allowing the attachment of MSCs and promote osteogenic differentiation of cells for delivering a mature osteoblastic cell population capable of rapidly forming bone. On the nanotube surfaces, a reoccurring trend was revealed that as we increased the diameter of the nanotubes, there was an increase in osteogenic biochemical activity and relative gene expression, Figure 9 (c).
Comparative graphs showing the influence of TiO2 nanotube diameter on osteogenic cell behavior. (a) Osteoblast functionality in terms of alkaline phosphatase activity or bone forming ability. (b) Osteogenic gene expression. RNA levels of alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN) are given for mesenchymal stem cells grown on different size diameter nanotubes. (c) Overall all trend for diameter effect on osteogenic cell behavior. As the nanotube diameter increases the osteogenic cell behavior is enhanced.
In a recent review article, Bettinger et al. claimed that the most palpable effect of nanotopography on cells is the distinct changes in cell geometry or shape (Bettinger, Langer, and Borenstein 2009). In fact, on the nanotube substrates with varying diameters, it was revealed that the osteoblast and mesenchymal stem cells have reacted to the nanostructures by changing shape. As the nanotube diameter increases we found a clear trend of increasing cell elongation, Figure 10. The stretching aspect ratio was as great as 12:1 (length:width) on the 100 nm diameter nanotubes. It can be assumed that the initial cell stretching and elongated shape of the adhering cells on the large nanotubes impacted the cytoskeletal (actin) stress. This is supported by the general notion that nanostructures (and the adhered protein configuration for example, Figure 3) act as an extracellular matrix which imposes physical forces and morphological changes to the cell (Chen 2008). It is probable that cells must elongate their bodies to find a protein deposited surface, extending across larger areas and thus eventually forming an exceedingly elongated shape on the 100nm diameter nanotubes (because of the sparse distribution, Figure 3). Thus altering the density of extracellular matrix (ECM) attachment sites or initial protein adhesion density affects the shape of adhered cells. It has been reported that the focal attachments made by the cells with their substrate determine cell shape which, when transduced via the cytoskeleton to the nucleus, result in expression of specific phenotypes (Boyan et al. 1996). In our results, we hypothesize that increasing nanotube diameters, changes the focal adhesion sites of the osteoblast and mesenchymal stem cells, increases the cell elongation, and increases osteogenic potential.
Interestingly, the cell nuclei also exhibit a somewhat similar trend of increased elongation with increasing nanotube diameter, with the 100nm TiO2 nanotubes showing the most significantly elongated nuclear shape (by ~20-25%) (data not shown). It can be hypothesized that the nucleus organelle elongation on the TiO2 nanotube surfaces is in part due to the gross elongated cytoskeletal morphology of the cell.
Quantification of cell elongation for osteoblast and mesenchymal stem cells on nanotubes with different diameters ranging from 30-100nm. There is a trend of increased elongation with increasing nanotube diameter.
It has been reported that cell shape maintained by the cytoskeletal assembly may also facilitate nuclear shape distortion which may promote DNA synthesis by releasing mechanical restraints to DNA unfolding, changing nucleocytoplasmic transport rates, or alternating the distribution and function of DNA regulatory proteins that are associated with the nuclear protein matrix (Maniotis, Chen, and Ingber 1997). A change in the nuclear structure has an effect on the 3-dimensional internal organization (Getzenberg et al. 1991). It appears that the osteoblasts and mesenchymal stem cells are adapting to the nanotube substrate nanotopography by organizing both external and internal shapes.
A concept developed by Dalby et al. (Dalby et al. 2008) suggests that MSC osteo-differentiation is determined by mechanotransductive pathways that were stimulated because the cell was under tension caused by way the cell was adhering and the shape it assumed due to the underlying nanostructure surface. Cell morphology/spreading dominates cell fate. McBeath et al. showed that commitment of stem cell differentiation to specific lineages is dependent upon cell shape (Mc Beath et al. 2004). In a single cell experiment with micropatterned surfaces the critical role of cell spread/shape in regulating cell fate was determined.
Nonetheless there is a need to better understand the mechanism by which such nanosurfaces direct MSC osteogenesis, and to optimize the culture conditions in order to maximize MSC expansion and differentiation. For bone growth, it requires cell proliferation and selective differentiation, and these processes are found to occur at different but discrete nanosurface topography conditions such as variations in nanotube diameter.
Establishing possible connections between mechanical properties of MSCs in differentiation is valuable to the field of mechanobiology. It can be speculated that natural forces that MSCs encounter in a physical environment does not need a strong cytoskeleton, however upon osteogenic differentiation, in which differentiation of MSCs become part of a larger bone structure that functions to provide both form and strength, the supporting structure of the cells are enhanced to enable function and withstand load bearing wear that bones endure. Understanding the physical characteristics of MSCs during differentiation may aid in the development of new biomaterials, which can potentiate the necessary mechanics of the cells for the advancement of tissue engineering.
In terms of the dimensions of the nanotubes in the osteoblast (bone cell) and mesenchymal stem cell (osteo-progenitor cell) studies, it was reported that a unique variation in cell behaviour even within a narrow range of nanotube diameters (Brammer et al. 2009; Oh 2009).The results of the previous research can be simply summarized: osteogenic functionality, both biochemical activity in osteoblasts and internal gene regulation of osteo-progenitor cells, were altered by the size/diameter of TiO2 nanotubes, as the nanotube diameter increased, the osteogenic function also increased. Such a trend can be utilized for improvement and control of the bone forming functionality for advanced orthopaedic implant technologies.
In these studies however, TiO2 nanotubes having a 1: 3 diameter: height aspect ratio was used, which was determined by the electrochemical anodization conditions including electrolyte solution, voltage, time, etc. While this current-state-of-the-art self assembly process of TiO2 anodization does not easily allow fabrication of TiO2 nanotubes with the diameter larger than ~100nm with the electrolyte used in this study, it would be interesting to study the effect of even larger diameter TiO2 nanotubes, possibly using a modified chemical process, on osteogenic cells.
Large diameter nanotubes prepared in 0.25 w/v% NH4F with various applied voltages. (A) SEM micrographs showing nanotube morphology by top view (a, c, e) and cross-sectional view (b, d, f). (B) Chart describing the effect of applied voltage on the physical nature of the nanotube dimensions.
Other methods for making large diameter (>100nm) TiO2 nanotubes using aqueous organic electrolytes with a future potential use as orthopaedic implant surfaces have been explored. Previously the anodization electrolyte method included aqueous dilute hydrofluoric acid. In an alternative fabrication method ammonium fluoride (NH4F) in an ethylene glycol solution as an electrolyte can be investigated. Figure 11 illustrates the SEM figures of TiO2 nanotubes prepared by 0.25 w/v% NH4F electrolyte at various anodization voltage for 17 hrs. The table in Figure 11 indicates the variations in applied voltage and the resultant physical dimensions of the fabricated nanotubes. By controlling the applied voltage, the diameter of the nanotubes could also be controlled. Nanotubes with diameters from ~130-225nm have been successfully prepared. Future work should include the use of large size nanotubes to find the most optimal stem cell osteogenesis and bone cell/tissue function.
In the future, nanostructured ceramics will be created that demonstrate even higher degrees of integration between materials and biology (Narayan et al. 2004). Future ceramic nanostructures may possess even more precisely tailored grain and/or pore sizes in order to obtain specific tissue interactions. For instance, loading nanoporous structures can provide an implant with biological functionalities (Cowan et al. 2003) are key prospects in deriving therapeutic based nanostructures that integrate and for wound healing, bone repair, and cardio vascular restoration, to name just a few. For example, silver and zinc-containing zeolites, marketed under the trade name AgION®, are currently being assessed for use in wound dressings. Figure 12 shows the idea of a “nanodepot” using the nanopores of the TiO2 nanotubes for loading biological agents.
a) Schematic illustration of “nanodepot” concept in TiO2 nanotubes. (b) Example of albumin protein elution from inner pores of TiO2 nanotube structures.
In the previous sections it has been shown that the physical environment of nanotopography has positive effects on cell behaviour, yet direct comparisons of nanotopographic surface chemistry has not been fully explored. For instance the possibility of nanotubes made of different materials, i.e. carbon, gold-Pd, zirconia, or tantalum for instance.
To date, a large part of the interest has remained on titanium oxide (TiO2) nanotubes because it is well known that titanium (Ti) is a biocompatible orthopedic material which provides an excellent osseointegrative surface. However, little notice has been given to zirconium oxide (ZrO2) nanotubes, which are formed via the similar self-assembled mechanism as TiO2 nanotubes, through an electrochemical anodization process (Berger et al. 2008). Zirconium (Zr) is similar to titanium in that it possesses a thin passivation oxide layer which makes it highly resistant to corrosion in bodily fluids (Oliveira et al. 2005). In fact, while the corrosion resistance and biocompatibility of certain Zr alloys are as good as those of Ti alloys, the mechanical properties have been found to be superior to those of the commonly used Ti-6Al-4V alloy (Kobayashi et al. 1995). Furthermore, a recent study by Bauer and co-workers demonstrated that mesenchymal stem cells react in the same manner to ZrO2 nanotubes, AuPd-coated TiO2 nanotubes, and as-formed TiO2 nanotubes (Bauer et al. 2009). Their results indicate that the cell response is chiefly due to nanotopographical cues instead of a specific surface chemistry pertaining only to TiO2.
There is a vast parametric space in which to explore novel nanostructures, nanopore dimensions, and material compositions for optimizing and advancing implant designs for desired tissue interactions.
The authors acknowledge financial support of this research by Iwama Fund at UC San Diego and UC Discovery Grant No. ele08-128656/Jin. This work was also partially supported by Postdoctoral Fellowship (for S. Oh) from the California Institute for Regenerative Medicine (CIRM).
As many as 60% of all episodes of small bowel obstruction (SBO) are caused by adhesions [1]. Adhesions are attachments of abdominal structures by internal scar tissue that are the result of healing of the peritoneum after it has been damaged, in most cases by surgery [2]. Adhesions can be filmy or dense and be present as an isolated band or as a ‘curtain’ or tangle with difficulty recognizing visceral structures. The degree of density and vascularization is traditionally classified using the Zühlke classification (Table 1) [3]. A more comprehensive and clinically relevant classification including projected locations of adhesions is the Peritoneal Adhesion Index (PAI) (Figure 1) [4, 5].
\nGrade | \nDescription | \n
---|---|
0 | \nNo adhesions or insignificant adhesions | \n
I | \nAdhesions that are filmy and easy to separate by blunt dissection | \n
II | \nAdhesions with beginning vascularization that can be dissected blunt but some sharp dissection is necessary | \n
III | \nAdhesions with clear vascularization that can only be dissected using sharp dissection | \n
IV | \nAdhesions which strongly attached organs, dissection is only possible by sharp dissection, damage of organs is hardly preventable | \n
Peritoneal adhesion index.
Adhesions develop in 89–93% of patients undergoing open abdominal or pelvic surgery [6, 7]. Incidence rates of adhesion formation are lower after minimally invasive surgery, 45–62% [7, 8]. Adhesions can also develop after other causes of peritoneal trauma, such as inflammatory conditions or radiotherapy [2]. The occurrence of adhesions does not only cause a lifelong risk of adhesive small bowel obstruction (ASBO). Other clinical consequences of adhesions are difficulties during reoperation, female infertility, and chronic visceral pain; making it the most common cause of long-term complications in peritoneal surgery [1]. The incidence of ASBO is 2–3% in the first years after surgery in all patients who undergo abdominal or pelvic surgery [1]. The risk of ASBO depends on the anatomical location of surgery and the extent of surgery and peritoneal injury [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. ASBO risk varies from 0.5% in abdominal wall surgery, 1.2% after upper gastrointestinal tract surgery to 3.2% in lower gastro-intestinal tract surgery and 4.2% in pediatric surgery [1].
\nGiven the high incidence of adhesions and adhesion-related complications, one would assume that every surgeon is aware of the risks of adhesions. However, awareness on the full size of the problem only arose in response to the publication of the Surgical and Clinical Adhesion Research (SCAR) study two decades ago. The SCAR large population based study demonstrated that one of three patients undergoing abdominal surgery is readmitted for a cause possibly related to adhesions [11]. Subsequently adhesion-related complications gained increasing awareness of clinicians, hospitals and vendors, and adhesion reduction strategies were introduced. Laparoscopic surgeons hypothesized that minimally invasive surgical techniques would reduce peritoneal injury and thereby could solve the problem of adhesion formation. Other strategies to reduce adhesion formation were the development of adhesion barriers, the banishment of powdered gloves, and the introduction of new sealing devices [12].
\nOver the past decades, minimally invasive surgery has become the standard approach in many surgical disciplines. The rapid introduction of minimally invasive surgery was largely fueled by short-term benefits such as quicker recovery, reduced pain, and better cosmetic outcome [13]. Furthermore, surgeons strongly believed in the effectiveness of minimally invasive surgical techniques to reduce adhesion formation and subsequent morbidity [14]. For this reasons adhesion barriers are only seldomly used in minimally invasive surgery [15], and are believed to be needed only in open surgery. Despite good evidence of effective reduction of adhesion formation and subsequent adhesion-related morbidity, the use of adhesion barriers in open surgery is also limited [16]. Reasons for not using adhesion barriers are the lack of trust in adhesion reduction, the expected limited impact on adhesion-related complications, and the costs of the barriers [15]. The limited use of adhesion barriers has slowed down the research and development of adhesion-prevention strategies in the past decade.
\nStudies on adhesion formation in minimally invasive surgery report a reduction of approximately 50% in the extent of postoperative adhesions compared with open surgery [7]. Unfortunately, trials comparing open and minimally invasive surgery have not been designed and powered to compare long-term adhesion-related outcomes [17]. Therefore, the effect of the broad implementation of minimally invasive surgery on clinically relevant outcome parameters such as ASBO and readmissions is unknown [17]. A reduction in adhesion formation, does not necessarily correlate with a proportionate reduction in the risk of ASBO; a single adhesive band may cause a life-threatening bowel obstruction, whereas extensive dense abdominal adhesions may be asymptomatic [18]. Nevertheless, potential benefits of minimally invasive surgery in preventing adhesion-related morbidity seem compelling.
\nMinimally invasive surgery may also play a role in the treatment of ASBO. Approximately 25% of patients with ASBO require surgery to resolve the bowel obstruction [1], and recurrence rates are high [19]. The minimally invasive approach is hypothesized to accelerate recovery, and might also reduce risk of regrowth of adhesions and subsequent recurrence of ASBO. A caveat is the small working space and vulnerability of the bowel caused by the distention of the obstructed bowel that could result in iatrogenic injuries. In this chapter, we discuss recent evidence on the effects of the introduction of minimally invasive surgery on the burden of adhesions and ASBO. We further discuss the role of minimally invasive surgery in the treatment of patients with ASBO. We end with a contemplation on the awareness of adhesion-related complications and the value of adhesion barriers in minimally invasive surgery.
\nThe vast majority of adhesions develop after abdominal or pelvic surgery, although adhesions can also form after abdominal and pelvic radiation and peritoneal inflammation [2]. Adhesions are associated with a lifelong risk of ASBO. Incidence and morbidity of ASBO might be somewhat difficult to estimate and compare between studies based on different definitions for ASBO. Most accepted definition of ASBO is an episode of SBO with the presence of adhesions confirmed during reoperation. However, operative confirmation of adhesions is often not possible because many ASBO episodes are managed non-operatively. Therefore a second definition of ASBO is commonly applied: an episode of SBO interpreted as matching ASBO on radiological imaging after excluding other potential causes of bowel obstruction e.g. hernia, tumor, bezoar.
\nIn a systematic review, the incidence of SBO by any cause after surgery is estimated 9% [1]. In 42 etiological studies on SBO, adhesions accounted for 56% of all SBO episodes, either by operative confirmation or by excluding all other potential causes of SBO [1]. The incidence of postoperative ASBO confirmed by surgery is estimated at 2.4%. Depending on the type of initial surgical procedure, the incidence varied between 0.5 and 4.2% [1]. As mentioned, this estimate is conservative because most episodes of ASBO are managed non-operative.
\nAnother way to estimate the burden of ASBO is based on population studies. In the SCAR study more than one in three patients were readmitted for a cause possibly related to adhesions, and more than 1 in 20 patients (6%) who underwent open abdominal or pelvic surgery were readmitted for a directly adhesion-related cause [11]. The most common diagnosis for a directly adhesion-related readmission was ASBO [11]. More recent population studies in the UK and USA show that ASBO remains a major contributor to the morbidity, mortality and costs related to emergency abdominal surgery. In the UK in 2016, 51% of all emergency laparotomies were for ASBO [20]. Similar results were found in the USA between 2008 and 2011, where SBO needing adhesiolysis belonged to the top 5 of emergency surgical procedures [21]. Given these numbers and the number of patients undergoing abdominal or pelvic surgery, the impact of ASBO on a population level is high.
\nASBO causes significant morbidity and a hospital admission for SBO is associated with 2.5% mortality [1]. Initial non-operative management of ASBO includes gastric decompression, fluid resuscitation and nil per os, which is successful in 70–90% [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]. In a sizable number of cases ASBO will result in emergency or delayed, after failed initial conservative management, abdominal surgery. Open or minimally invasive adhesiolysis to resolve the obstruction is associated with a incidence of 6–20% enterotomies [24, 25]. In general, complex adhesiolysis is associated with bleeding, sepsis, wound infections and increased mortality, even in the absence of bowel injury [26]. Mean length of hospital stay for ASBO ranges from 4 to 13 days and generally depends the type of treatment and the treatment complications [1].
\nBoth operative and conservative management of ASBO are associated with a risk of recurrent ASBO. Operative management includes repeated peritoneal injury with risk of adhesion reformation and re-ASBO. Non-operative management of ASBO does not dissolve abdominal adhesions and harbors the risk of a new episode of ASBO. In a recent study of patients presenting with a first episode of ASBO, operative management was associated with a lower risk of recurrence compared with non-operative management (13% vs. 21%) after a median follow-up of 3.6 years [19]. The study also showed an increased risk of ASBO with every previous episode of ASBO in accordance to findings done 25 years ago [27]. Also the time between episodes of ASBO decreases with an increase in number of episodes [19]. Despite the higher recurrence rate after conservative treatment, current guidelines still recommend a trial of non-operative management of ASBO in order to avoid the risk of complications associated with surgical intervention [28].
\nEffort is made to predict the severity of ASBO using peri-operative scores [29, 30]. However, the scores are not widely adopted for clinical use. The American Association for the Surgery of Trauma (AAST) developed a score based on clinical, imaging, operative and pathologic criteria to grade disease severity of ASBO [31, 32]. The AAST grade uses clinical criteria (flatus, bowel sounds abdominal distention), pathologic criteria (bowel perforation), imaging criteria on CT (intestinal distention, transition point, contrast flow) and operative criteria (intestinal distention, impeding bowel compromise, peritonitis) to define the grade of ASBO on a scale from 1 to 4. A higher AAST score for emergency ASBO is associated with an increase in length of hospital stay, pneumonia, and more severe complications [33]. Recently the Clinical Adhesion Score (CLAS) was developed, measuring the full spectrum of the long-term burden of adhesion formation in post-operative patients. CLAS calculates the overall morbidity based on four domains: ASBO, difficulties during reoperation, female infertility or subfertility, and chronic abdominal pain (data not yet published). Evaluation of current and new adhesion prevention strategies regarding long-term clinical efficacy e.g. ASBO could benefit from using CLAS.
\nThe economic burden of ASBO is high. Operative management is the single most important determinant of costs. However, based on fewer recurrences of ASBO after surgical treatment, surgery may save costs at the long term [34]. Several studies have been reported regarding the treatment costs of ASBO. Most have important limitations reporting part of the costs or costs based on reimbursement prices rather than true healthcare costs [35, 36, 37]. We modeled in a recent study, costs for ASBO in the Netherlands using a micro-costing method including costs of length of stay, ICU days, operative time, medication, parenteral feeding, imaging studies and laboratory studies [38]. This modeling revealed total healthcare costs of patients operated for ASBO of €16305 (SD €2513) with a mean hospital stay of 16.0 ± 11 days. For non-operatively treated patients costs would be €2277 (SD €265) with a mean hospital stay of 4.0 ± 2.0 days. The majority of the costs were due to ward stay, operative time, ICU stay and (parental) feeding. All surgical procedures for ASBO in this study consisted of open adhesiolysis. Costs estimated in this study were higher compared to previous estimates of treatment costs for ASBO with comparable lengths of stay and, as a result of its design better reflecting reality [35, 36, 37]. In the study we adhered to international guidelines for the diagnosis and treatment of ASBO increasing generalizability of outcomes for developed countries. Nevertheless costs may vary among countries due to differences in admission and discharge policies, and prices of diagnostics, materials, medication and feeding.
\nIt has been suggested from a few studies that the decreased adhesion formation after minimally invasive surgery associates with a lower incidence of ASBO. This decrease seems limited compared to open surgery as concluded from one systematic review and one trial reported by our group [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]. Differences in definitions of ASBO used, types of procedures, outcome parameters and length of follow-up in the studies, preclude a firm conclusion on the beneficial effect of minimally invasive surgery on development of ASBO.
\nTo estimate the impact of minimally invasive surgery at a population level on adhesion-related complications, ASBO in particular, our group recently reported the results of the SCAR update study [39]. Over 72,000 patients, who were operated between June 2009 and June 2011, were followed for a minimum of 5 years. Readmissions were classified, according to the initial SCAR study (1999), as directly-related to adhesions e.g. adhesive small bowel obstruction, possibly related to adhesions, e.g. any small bowel obstruction and reoperations potentially complicated by adhesions e.g. right hemicolectomy years after an appendectomy. Approximately 30% of all index procedures were minimally invasive. Patients who underwent minimally invasive surgery were readmitted less frequently for directly related causes compared with patients after open surgery (1.7% vs. 4.3%). Possibly related readmissions and reoperations potentially complicated by adhesions were also less frequent (16.0% vs. 18.2% and 8.6% vs. 15.0%). Multivariate analysis revealed a 32% reduction in directly adhesion-related readmissions associated with minimally invasive surgery. Readmission rates were similar when comparing patients with open surgery in the SCAR and those in the SCAR update study. The overall small differences found in readmission rates could be explained by the difference in follow-up, 10 years in the SCAR study and 5 years in the SCAR update study. Despite the finding of a small reduction in readmission rates after initial minimally invasive surgery, the overall burden of adhesion-related readmissions on a population level remains high.
\nTo further elaborate differences in adhesion-related readmissions between minimally invasive and open surgery, we analyzed patients with colorectal procedures (data not yet published). This type of surgery is known for its adhesion formation propensity and associated morbidity. Over 15,000 patients underwent colorectal surgery of whom almost one-third with a minimally invasive approach. For open colorectal surgery readmission rates were comparable between the SCAR study and the SCAR update study. Minimally invasive colonic and/or rectal surgery reduced the total number of directly adhesion-related readmissions. However in patients who underwent a (sub)total colectomy readmission rates were over 15% irrespective of an open or minimally invasive approach. Minimally invasive surgery did not reduce adhesion-related complications in rectal procedures. We concluded that an extended colectomy and rectal resection do not benefit from minimally invasive surgery regarding adhesion-related complications. We hypothesized that the large extent of the dissection and injury to the visceral and lateral parietal peritoneum needed in both surgical techniques abolishes the preventive effect of the minimally invasive technique on adhesion formation to the ventral peritoneum, where the injury is relatively limited for both approaches.
\nThe SCAR update study has demonstrated that minimally invasive surgery is associated with less adhesion-related readmissions. Hence, the overall burden of adhesion-related readmissions on a population level remains high. Adhesion formation therefore continues to be a challenge in abdominal surgery, also in the minimally invasive era. Minimally invasive procedures were only performed in approximately one-third of procedures in 2009–2011, whereas currently in the Netherlands about 75% of colonic resections are performed minimally invasive (by laparoscopy or robot) [40]. On a population base a further decline in adhesion-related complications can be expected with an increase of minimally invasive abdominal operations. However, we like to warn against unbridled optimism regarding the overall impact of minimally invasive surgery on the burden of adhesions because open surgery is still being preferred when a complicated condition is expected in the abdominal cavity e.g. after multiple previous procedures, with large inflammatory mass or locally advanced cancer [41]. Many of these conditions are complex specifically due to presence of adhesions at baseline surgery and the need to perform adhesiolysis before entering the operative area. It is known that the propensity to reform adhesions after adhesiolysis is higher than de novo adhesion formation.
\nAdequate management of ASBO depends on an initially correct diagnosis. Although ASBO is a common diagnosis with clear signs and symptoms, misdiagnosis and delayed diagnosis are a substantial clinical problem. Up to 50% of older patients are initially not adequately diagnosed [42]. Failure to diagnose represents 70% of malpractice claims in ASBO [43, 44]. In this regard it is important to note that patients with ASBO can initially present themselves to a variety of physicians, including general practitioners, surgeons, internal medicine physicians, geriatricians and gastroenterologists. To improve diagnosis of ASBO, multiple specialists need to be involved in practice guidelines and protocols.
\nBased on expert opinion the diagnosing of ASBO includes a medical history with an assessment of potential causes of SBO, e.g. previous abdominal surgery, inflammatory bowel disease, important symptoms such as vomiting, absence of stools or flatus, intermittent colicky abdominal pain and abdominal distention. Common pitfalls in diagnosing ASBO are the less prominent pain present in the elderly [42], reporting of watery diarrhea by patients with an incomplete obstruction and normal stool passage in the first days after onset due to stool still present in the colon.
\nThe recent update of the international guidelines for diagnosis and management of ASBO gives the current best available evidence for management of ASBO once the diagnosis of bowel obstruction has been established [28]. The first priority in management is to establish the cause of obstruction and to determine if urgent surgical treatment is required. ASBO is the single most common cause for SBO, the differential diagnosis includes strangulated abdominal wall or groin hernia, tumor, paralysis, constipation or bezoars. Laboratory tests should include blood count, CRP, electrolytes, creatinine and lactate. Imaging studies can include water-soluble contrast studies or computer tomography (CT) scans. CT scan is the preferred imaging technique for the diagnosis of ASBO, it can accurately rule out other causes of obstruction and identify patients who might require emergency surgery [28]. Water-soluble contrast enhances the diagnostic accuracy of CT scans. Signs that might suspect ASBO on imaging studies are an abrupt change in bowel diameter and the exclusion of other causes of SBO. The value of plain X-rays is limited [28].
\nUrgent surgery is required in case of signs of ischemia, perforation or strangulation of the bowel, generalized peritonitis and/or hemodynamic instability. No single test is highly sensitive for ischemia and strangulation. Sensitivity of physical examination for the detection of strangulation is only 48% in experienced hands [45]. Laboratory tests indicating peritonitis or ischemia are a CRP above 75 and a white blood cell count above 10.000/mm3 [45, 46, 47]. Again, a CT scan is most accurate in assessing strangulation and perforation and the need for emergency surgery [28]. CT abnormalities indicating strangulation or perforation are free intraperitoneal air or fluid, closed loop obstruction, mesenteric edema or engorgement, mesenteric swirling, pneumatosis intestinalis, decreased or lack of bowel enhancement or thickened bowel wall [48, 49, 50].
\nIf bowel obstruction is caused by adhesions, and signs of peritonitis, ischemia, and strangulation are absent, initial conservative treatment is reportedly safe. Conservative treatment is successful in 70–90% of all episodes of ASBO [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]. Conservative treatment of ASBO consists of nil per os and decompression of the gastro-intestinal tract using a naso-gastric tube. Further management includes fluid resuscitation, correction of electrolyte disturbances, nutritional support and prevention of aspiration. Optimal duration of a conservative trial is debated; prolonged management for more than 72 h has been associated with adverse outcomes and increased mortality [20, 51, 52, 53, 54]. Water-soluble contrast studies seem useful in the follow-up of conservative management of ASBO. If contrast has not reached to colon 24–48 h following administration, continuation of conservative management is likely to fail and surgical management should be considered [28].
\nAn algorithm for the diagnosis and treatment of ASBO is presented in Figure 2 [28].
\nAlgorithm for the diagnosis and treatment of ASBO.
Operative treatment of ASBO historically comprises an explorative laparotomy with adhesiolysis. The increased use of minimally invasive surgery has raised the question whether minimally invasive surgery is feasible and effective for the treatment of ASBO. Benefits of minimally invasive adhesiolysis are reduction of peritoneal injury possibly resulting in less adhesion reformation, a quick recovery and minimal post-operative pain. Twenty-five years ago the first cases of minimally invasive surgery for treatment of ASBO have been described [55]. Thereafter a few series were reported but adequate comparative trials are scarce [56, 57, 58, 59, 60]. Minimally invasive surgery for ASBO is challenging because there is little laparoscopic working space due to the distended bowel. Also visibility can be hampered by multiple adhesions. There are concerns that minimally invasive surgery increases the risk of iatrogenic bowel perforations [57]. Suitability of minimally invasive surgery for ASBO further depends on patient characteristics. In case of hemodynamic instability open surgery is required because patients cannot tolerate the pneumoperitoneum.
\nOne randomized trial comparing minimally invasive and open surgery for ASBO has been performed [56]. Only patients with a high suspicion of a single adhesive band causing the obstruction were included. Patients with confirmed or suspected peritoneal carcinosis, known multiple adhesions, previous open surgery for endometriosis, aorta, iliac vessels or Crohn’s disease, previous generalized peritonitis, abdominal malignancy, previous abdominal radiotherapy or recent operations within 30 days were all excluded. Patients started with conservative management of ASBO. If the obstruction did not resolve patients were randomized between open and laparoscopic adhesiolysis. The trial was open label, therefore patients and care providers were not blinded. During 5 years 566 patients were included in the study, 104 patients underwent surgery, 51 were randomly assigned to the open surgery group, and 53 to the laparoscopic surgery group. Patients in the laparoscopic group had a shorter length of stay (4.2 days) compared with the open group (5.5 days). Mortality and postoperative complications did not differ between the groups.
\nThe few matched cohort studies comparing minimally invasive and open surgery for ASBO reported comparable results to those of the trial mentioned above [59, 60]. There seems a trend towards a faster recovery in selected patients. Studies showed no major differences in complications or mortality. A few studies specifically addressed the potential drawbacks of the minimally invasive approach and suggested an increased risk of bowel injury [59]. Notably, the non-matched cohorts frequently claim large beneficial effects of the laparoscopic approach [40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58]. However, these studies have a high risk of various types of selection bias, mainly excluding patients who are more sick or are suspected of multiple adhesions.
\nIt seems that minimally invasive adhesiolysis holds promise for patients with signs of a single adhesive band and an uncomplicated disease course. Further studies are needed to identify patients who can benefit from minimally invasive adhesiolysis and patients who can be harmed by minimally invasive treatment for ASBO.
\nMorbidity of adhesion formation in minimally invasive surgery is often underestimated. Less than 25% of surgeons and 5–83% of gynecologists routinely inform their patients about adhesions and the life term risk of adhesion-related complications [14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62]. However, recent evidence shows that adhesion-related morbidity remains high in the minimally invasive era [39]. Not informing patients about the risk of adhesions might therefore be considered negligent. Increased awareness of adhesions might create an urge for the development and refinement of adhesion prevention strategies.
\nAwareness of adhesions may improve by growing awareness for intra-operative complications in general. Impact of adhesions on the operative course of reoperations for ASBO or other indications is often underreported. In a prospective comparison of operative notes and observation by an independent researcher, one in seven iatrogenic bowel injuries was not reported in operative notes, and almost one in three minor injuries [63]. In recent years, there is increasing scientific interest in the consequences of intra-operative events. IAEs are associated with 40% more hospital admissions, a twofold higher readmission rate, and with worse post-operative outcome [64, 65, 66, 67, 68, 69, 70]. Recently the Classification of Intraoperative Complications (CLASSIC) has been developed as a new tool for systematic classification for intra-operative complications (iAEs) [71]. CLASSIC defines iAEs as any deviation from the ideal intraoperative course, including technical failures, surgical and anesthesiological difficulties. The score has been update to five grades of severity (https://clinicaltrials.gov/ct2/show/NCT03009929). Lysis of adhesions at reoperations is associated with post-operative increase of sepsis, intra-abdominal complications, wound infections, longer hospital stay, and higher hospital costs [26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72]. As such, adhesiolysis qualifies as an iAE if adhesiolysis is not the intended surgical procedure. We currently investigate the contribution of adhesiolysis and associated intra-operative complications e.g. bleeding, inadvertent enterotomy to the CLASSIC.
\nRecent published guidelines may also increase awareness of adhesions and treatment of ASBO [28]. An old saying on ASBO is ‘you must not let the sun rise on ASBO’, all patients presenting with ASBO were operated if conservative management failed to resolve the bowel obstruction within 24 h. Recent insights report that a conservative trial can safely be prolonged to 72 h [51, 52]. The current guideline states that conservative treatment should be instigated in all patients without signs of ischemia, perforation or strangulation of the bowel, generalized peritonitis and/or hemodynamic instability [28]. Contradictory, some studies report lower recurrence rates of ASBO after surgical management of ASBO [19, 20, 21, 22, 23, 24, 25, 26, 27]. A further disadvantage of prolonged conservative management is the further clinical deterioration of highly comorbid patients who receive starvation treatment for a few days [73]. Minimally invasive surgery could change the paradigm again towards earlier surgical intervention because of faster recovery, reduced length of hospital stay and the mentioned lower recurrence rates of ASBO.
\nConsidering the high impact of adhesion-related complications on a population level that is not substantially decreased by minimally invasive surgery, there is a pressing need to develop new adhesion reduction strategies.
\nUntil now the most promising approach for reduction of adhesion formation is routinely applying an adhesion barrier. Adhesion barriers are bioresorbable liquids, gels or films that keep injured peritoneal wound surfaces separated. During separation the peritoneal wound can heal with restoration of peritoneal tissue morphology and function without ‘scarring’ (adhesions). A large systematic review and meta-analysis in 2014 of 28 trials (n = 5191) showed benefits of several adhesion barriers in predominantly open abdominal surgery [16]. However, adhesion barriers are seldomly applied in abdominal or pelvic surgery [14]. Only 1 in 7 surgeons ever uses adhesion barriers [14]. Reluctance of surgeons to use adhesions barriers seems caused by doubts about cost-effectiveness and the need and possibility of adhesion prevention in minimally invasive surgery.
\nCost-effectiveness of adhesion prevention in minimally invasive surgery is an important perquisite for implementation in every day practice. We performed a modeling study on cost-effectiveness of adhesion barriers in minimally invasive procedures with a high risk of adhesion formation [74]. Two strategies were compared: current clinical practice (colorectal surgery without the use of an adhesion barrier) and colorectal surgery with the use of an adhesion barrier (hyaluronate carboxymethylcellulose). Whilst hyaluronate carboxymethylcellulose as such is not applicable in minimally invasive surgery and a gel form has not properly been studied in minimally invasive surgery, probabilities were extrapolated from data of open colorectal surgery. Probability estimates were derived from literature. Costs of treatment of ASBO were derived from our previous report [38]. Cost of hyaluronate carboxymethylcellulose was estimated on $630, based on the mean number of films used in studies on hyaluronate carboxymethylcellulose [12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75]. We concluded that using an adhesion barrier was more effective than not using a barrier in minimally invasive surgery, but it was more expensive. However, mean expected direct healthcare costs in the 4 years following index surgery increased with only $163 per patient. Cost estimates in this modeling study only included direct health care costs. Societal costs (e.g. absence from work) were not modeled in this study. Therefore an increase of $163 in direct health care may be neglectable considering potential gain in societal costs. Further research is needed on long term savings regarding socio-economic costs with adhesion barriers also including the new SCAR update data of minimally invasive surgery.
\nAn important limitation of most barriers is the inability to properly use these in minimally invasive surgery. Most barriers were developed more than two to three decades ago and were films intended for use in open surgery. This limitation and the disregard needing barriers in minimally invasive surgery have impeded implementation and continued research and development of barriers suitable for minimally invasive surgery (and open surgery). Recently some new barriers have been developed suitable for minimally invasive surgery. Studies on these new barriers are performed mostly in gynecologic populations, and show effectiveness reducing adhesions [76, 77]. The important next step in adhesion prevention is the development of a new generation of barriers suitable for minimally invasive use in general surgery [78, 79]. Using increased knowledge of the pathophysiology of adhesions, new barriers consist of bioactive and targeted technology e.g. modulation of inflammation [2]. Pilpel and colleagues developed a liquid solution modulating the fibrin matrix which is generated by the hemostatic system after peritoneal injury [80]. This novel therapy is currently tested in animal models. Roberston and colleagues are testing a drug (L-Alanyl-L-Glutamine) to regulate the formation of adhesions due to hypoxia and oxidative stress caused by surgical injury of the vascular supply to the tissue caused by surgical intervention [81]. The first results of this drug in a double-blinded placebo controlled study show that L-Alanyl-L-Glutamine is safe to use and is effective at reducing adhesion formation after laparoscopic myomectomies [82]. Definitive results from this study are expected in due time. When proven safe, effective and affordable in patients, these new bioactive and targeted technology agents should be administered during index minimally invasive surgery to break the sequence of intra- and postoperative adhesion-(re)formation related complications.
\nAdhesion-related morbidity remains a clinically relevant problem in the minimally invasive era. Minimally invasive surgery is associated with only a modest reduction in adhesion-related readmissions and incidence of ASBO. The growing body of scientific evidence provides the clinician with a firm guideline for the diagnosis and treatment of ASBO. Minimally invasive surgery in the management of ASBO appears to be safe and effective alternative to open adhesiolysis, however in a very selected patient group. To allow as many patients as possible to benefit from a minimally invasive approach future research should focus on the selection criteria for minimally invasive surgery in ASBO. Adhesion-related morbidity is often underestimated and complications of adhesiolysis underreported. Raising awareness of adhesions therefore remains important. Using newly proposed scores for intraoperative complications, may increase awareness for the intra-operative events caused by adhesions. Adhesion barriers can safely reduce adhesion formation, are cost-effective in open colorectal surgery and effective with slightly higher costs in minimally invasive surgery. Future research should focus on new bioactive barriers that are easily applicable in minimally invasive abdominal surgery and safe to use. Preventing adhesions during first minimally invasive surgery is key to break the sequence of intra- and postoperative adhesion (re)formation related complications.
\nThe authors declare no conflict of interest.
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Given, the obvious risk of loss of diversity, it is increasingly necessary to take actions concerning preservation, in which safety features are necessary for measuring the variation of diversity in space and time. The aim of this study was to evaluate the structure and diversity in the arboreal component and natural regeneration in an area of Araucaria Forest in Southern Brazil. The vegetation sampling was performed by analyzing 180 subunits of 10 × 10 m, where all the arboreal individuals and natural regeneration were inventoried. Different alpha and beta indexes of diversity were calculated. The Margalef, Shannon, and the Beta indexes were underestimated, possibly influenced by the size of sample unit. Index Menhinick represented the diversity in a very real form, even in small sampling units. The indexes of Simpson and MacIntosh denote low dominance and the equity indexes showed high uniformity in species.",book:{id:"5934",slug:"selected-studies-in-biodiversity",title:"Selected Studies in Biodiversity",fullTitle:"Selected Studies in Biodiversity"},signatures:"Maria Raquel Kanieski, Solon Jonas Longhi and Philipe Ricardo\nCasemiro Soares",authors:[{id:"219216",title:"Dr.",name:"Maria Raquel",middleName:null,surname:"Kanieski",slug:"maria-raquel-kanieski",fullName:"Maria Raquel Kanieski"},{id:"220250",title:"Dr.",name:"Solon Jonas",middleName:null,surname:"Longhi",slug:"solon-jonas-longhi",fullName:"Solon Jonas Longhi"},{id:"220251",title:"Dr.",name:"Philipe Ricardo",middleName:null,surname:"Casemiro Soares",slug:"philipe-ricardo-casemiro-soares",fullName:"Philipe Ricardo Casemiro Soares"}]},{id:"46541",title:"Ecosystem Biodiversity of India",slug:"ecosystem-biodiversity-of-india",totalDownloads:3381,totalCrossrefCites:1,totalDimensionsCites:4,abstract:null,book:{id:"3821",slug:"biodiversity-the-dynamic-balance-of-the-planet",title:"Biodiversity",fullTitle:"Biodiversity - The Dynamic Balance of the Planet"},signatures:"Vivek Khandekar and Anita Srivastava",authors:[{id:"51372",title:"Dr.",name:"Anita",middleName:null,surname:"Srivastava",slug:"anita-srivastava",fullName:"Anita Srivastava"},{id:"170148",title:"Dr.",name:"Vivek",middleName:null,surname:"Khandekar",slug:"vivek-khandekar",fullName:"Vivek Khandekar"}]},{id:"38697",title:"Floral and Avifaunal Diversity of Thol Lake Wildlife (Bird) Sanctuary of Gujarat State, India",slug:"floral-and-avifaunal-diversity-of-thol-lake-wildlife-bird-sanctuary-of-gujarat-state-india",totalDownloads:3987,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"2719",slug:"biodiversity-enrichment-in-a-diverse-world",title:"Biodiversity Enrichment in a Diverse World",fullTitle:"Biodiversity Enrichment in a Diverse World"},signatures:"Jessica P. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. 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For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. 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His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. 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