Collagen types, forms and distribution [6].
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6557",leadTitle:null,fullTitle:"Structural Insufficiency Anomalies in Cardiac Valves",title:"Structural Insufficiency Anomalies in Cardiac Valves",subtitle:null,reviewType:"peer-reviewed",abstract:"Heart valves are the basic functional structure of the heart to obtain, sustain, and maintain blood circulations in the body without energy loss, allowing blood regurgitation or obstructing blood flow. There are two basic designs of heart valves: actively protected via subvalvular apparatus (atrioventricular valves) and passively strengthened (ventriculoarterial valves). The embryologic and morphologic development of heart valves is the key stage to continue normofunctional structure and physiological behavior. Fetal anomalies, embryologic defects, or non-development pathologies may damage the structure of heart valves and cause functional deterioration at different grades. In this book, we have focused on specific pathologies, which require special knowledge and treatment modalities.",isbn:"978-1-78923-767-2",printIsbn:"978-1-78923-766-5",pdfIsbn:"978-1-83881-550-9",doi:"10.5772/intechopen.71281",price:119,priceEur:129,priceUsd:155,slug:"structural-insufficiency-anomalies-in-cardiac-valves",numberOfPages:162,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"108417ca71fe7374aee81d789c981dc1",bookSignature:"Kaan Kirali",publishedDate:"October 3rd 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6557.jpg",numberOfDownloads:7654,numberOfWosCitations:2,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:6,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:10,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 4th 2017",dateEndSecondStepPublish:"January 4th 2018",dateEndThirdStepPublish:"February 23rd 2018",dateEndFourthStepPublish:"May 14th 2018",dateEndFifthStepPublish:"July 13th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"155565",title:"Prof.",name:"Kaan",middleName:null,surname:"Kırali",slug:"kaan-kirali",fullName:"Kaan Kırali",profilePictureURL:"https://mts.intechopen.com/storage/users/155565/images/3020_n.jpg",biography:"Professor Dr. Kaan Kırali completed his training in Koşuyolu Heart and Research Hospital, Istanbul, Turkey. He became a consultant surgeon in 1997, and has published more than 90 international and 160 national articles. He is the pioneer of awake complete CABG with BIMA. He is also one of the pioneers of aortic root surgery. He has developed a new aortotomy incision, which makes aortic valve interventions simpler. He completed a master’s program on preventive medicine in Istanbul University, Istanbul, Turkey. Dr. Kırali is the Head of the Department of CVS in Sakarya University, Sakarya, Turkey, and the Chief of the Department of CVS in Koşuyolu Heart and Research Hospital, Istanbul, Turkey. He is also in charge of the heart transplantation mechanical assist device program, and a member of several international societies.",institutionString:null,position:"Chief of the department",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"9",totalChapterViews:"0",totalEditedBooks:"4",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"170",title:"Cardiology and Cardiovascular Medicine",slug:"cardiology-and-cardiovascular-medicine"}],chapters:[{id:"61973",title:"Structure-Function Relationship of Heart Valves in Health and Disease",doi:"10.5772/intechopen.78280",slug:"structure-function-relationship-of-heart-valves-in-health-and-disease",totalDownloads:1186,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:1,abstract:"The heart valves allow unidirectional and unobstructed passage of blood without regurgitation, trauma to blood elements, thromboembolism, and excessive stress concentrations in the leaflet and supporting tissue. In order to achieve this, the heart valves rely of their unique macroscale anatomy, histoarchitecture and ultrastructural features that allow them to accommodate repetitive changes in shape and dimension throughout the cardiac cycle. This chapter is focused on the structure-function relationship of the heart valves, with particular focus on the aortic and mitral valves, discussing how the biochemical, histoarchitectural and anatomical features influence valvular function during the cardiac cycle and how valvular function dictates valvular architecture and ECM constitution. The chapter examines the structure-function relationship of valvular tissue by correlating its microscale histoarchitecture and biochemical constitution to its mesoscale biomechanics and macroscale function during the cardiac cycle. Moreover, the chapter examines the influence of pathological alterations on the histoarchitectural and biochemical characteristics of the valves on their biomechanical behavior.",signatures:"Sotirios Korossis",downloadPdfUrl:"/chapter/pdf-download/61973",previewPdfUrl:"/chapter/pdf-preview/61973",authors:[{id:"55700",title:"Dr.",name:"Sotirios",surname:"Korossis",slug:"sotirios-korossis",fullName:"Sotirios Korossis"}],corrections:null},{id:"60904",title:"Mitral Valve Insufficiency, a Constituent of Left Atrial Myxoma: Pathobiology, Physiopathology, and Pathophysiology of Left Atrial Myxoma; Are Long-Term Results Still Feasible?",doi:"10.5772/intechopen.76510",slug:"mitral-valve-insufficiency-a-constituent-of-left-atrial-myxoma-pathobiology-physiopathology-and-path",totalDownloads:873,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Iroegbu Chukwuemeka Daniel, Zhongxin Zhou, Zhang Hao and\nJindong Liu",downloadPdfUrl:"/chapter/pdf-download/60904",previewPdfUrl:"/chapter/pdf-preview/60904",authors:[{id:"238805",title:"Dr.",name:"Chukwuemeka Daniel",surname:"Iroegbu",slug:"chukwuemeka-daniel-iroegbu",fullName:"Chukwuemeka Daniel Iroegbu"},{id:"243692",title:"Prof.",name:"Zhou",surname:"Zhongxin",slug:"zhou-zhongxin",fullName:"Zhou Zhongxin"},{id:"243695",title:"Prof.",name:"Jindong",surname:"Liu",slug:"jindong-liu",fullName:"Jindong Liu"},{id:"243696",title:"Dr.",name:"Hao",surname:"Zhang",slug:"hao-zhang",fullName:"Hao Zhang"}],corrections:null},{id:"60840",title:"Cardiac Dyssynchrony as a Pathophysiologic Factor of Functional Mitral Regurgitation: Role of Cardiac Resynchronization Therapy",doi:"10.5772/intechopen.76605",slug:"cardiac-dyssynchrony-as-a-pathophysiologic-factor-of-functional-mitral-regurgitation-role-of-cardiac",totalDownloads:916,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Functional mitral regurgitation, a common problem in patients with left ventricular systolic dysfunction, has a strong negative impact on prognosis. Beneficial effects of surgical treatment in functional mitral regurgitation are still a matter of debate. Thus, cardiac dyssynchrony, a factor involved in functional mitral regurgitation pathophysiology, may become a therapeutic target in patients with this condition. This part of the book presents the pathophysiology of functional mitral regurgitation as a dynamic process, with particular emphasis on cardiac dyssynchrony, as both a contributor to functional mitral regurgitation and a target for cardiac resynchronization therapy. The underlying mechanisms of success and failure in the resynchronization therapy are discussed, along with therapeutic approaches to symptomatic patients with severe left ventricular dysfunction and significant persistent functional mitral regurgitation.",signatures:"Barbara Brzezińska and Krystyna Łoboz-Grudzień",downloadPdfUrl:"/chapter/pdf-download/60840",previewPdfUrl:"/chapter/pdf-preview/60840",authors:[{id:"239267",title:"Ph.D.",name:"Barbara",surname:"Brzezińska",slug:"barbara-brzezinska",fullName:"Barbara Brzezińska"},{id:"240065",title:"Dr.",name:"Krystyna",surname:"Łoboz-Grudzień",slug:"krystyna-loboz-grudzien",fullName:"Krystyna Łoboz-Grudzień"}],corrections:null},{id:"61704",title:"Mitral Valve Prolapse in Pregnancy: Modern Concept",doi:"10.5772/intechopen.76692",slug:"mitral-valve-prolapse-in-pregnancy-modern-concept",totalDownloads:982,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter presents the recent literature data data on the problems of etiopathogenesis, cardiac, and obstetric risk of mitral valve prolapsus, as well as the tactics of patients with this pathology. Modern views on the role of genomic, genetic disorders, and metabolomics in violations valvular structures in the etiology and pathogenesis of clinical manifestations of the mitral valve prolapsus. In addition, the data on the peculiarities of pregnancy and childbirth in women with mitral valve prolapsus (miscarriage, cervical incompetence, preeclampsia, fetal growth restriction, placental insufficiency, labor anomaly, and postpartum hemorrhage) are studied. However, ambiguous and sometimes conflicting data on the relationship and the incidence of these complications with mitral valve prolapsus require further research to determine the set of diagnostic and preventive measures.",signatures:"Ignatko Irina Vladimirovna, Strizhakov Leonid Alexandrovich,\nRodionova Alexandra Mihailovna and Martirosova Alina Lorisovna",downloadPdfUrl:"/chapter/pdf-download/61704",previewPdfUrl:"/chapter/pdf-preview/61704",authors:[{id:"229571",title:"Prof.",name:"Ignatko Irina",surname:"Vladimirovna",slug:"ignatko-irina-vladimirovna",fullName:"Ignatko Irina Vladimirovna"},{id:"246412",title:"Prof.",name:"Leonid",surname:"Strizhakov",slug:"leonid-strizhakov",fullName:"Leonid Strizhakov"},{id:"246472",title:"Dr.",name:"Alexandra",surname:"Rodionova",slug:"alexandra-rodionova",fullName:"Alexandra Rodionova"}],corrections:null},{id:"61608",title:"Bicuspid Aortic Valve",doi:"10.5772/intechopen.76643",slug:"bicuspid-aortic-valve-2018",totalDownloads:862,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Bicuspid aortic valve (BAV) is one of the most common congenital diseases, affecting 1–2% of the general population. Although most of them are sporadic, some familial cases have also been detected. BAV is a complex developmental and progressive pathology, which may present with various clinical findings from newborn to adulthood. It may be suspected during cardiac auscultation or may be diagnosed by echocardiography incidentally. Some BAV cases may remain symptomless for years, with findings like valvular stenosis, insufficiency, or dilatation in the ascending aorta, whereas some others may present with early severe aortic valve dysfunction, premature congestive heart failure, and aortic aneurysms even in the newborn period. Such heterogeneous presentations of BAV phenotypes may be associated with congenital, genetic, and/or connective tissue abnormalities. The natural course of BAV is nonpredictable, it may lead to severe morbidity and mortality.",signatures:"Ayşe Inci Yıldırım and Aysu Türkmen Karaağaç",downloadPdfUrl:"/chapter/pdf-download/61608",previewPdfUrl:"/chapter/pdf-preview/61608",authors:[{id:"33985",title:"Dr.",name:"Ayse",surname:"İnci Yıldırım",slug:"ayse-inci-yildirim",fullName:"Ayse İnci Yıldırım"},{id:"232642",title:"Dr.",name:"Aysu",surname:"Türkmen Karaağaç",slug:"aysu-turkmen-karaagac",fullName:"Aysu Türkmen Karaağaç"}],corrections:null},{id:"60248",title:"Contemporary Surgical Options for the Aortic Root",doi:"10.5772/intechopen.75816",slug:"contemporary-surgical-options-for-the-aortic-root",totalDownloads:851,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Aortic root pathology is diverse, and it is the most common cause of aortic valve incompetence in the United States. Aortic root surgery is undergoing continuous development and refinements. From the original description of Bentall on aortic root replacement, many advances have been made in the field of aortic root surgery. The surgical armamentarium available today provides advanced repair options as well as replacement options for the aortic root. The aim of this chapter is to provide an insight into the basics of aortic root surgery as well as to further describes the current up-to-date solutions for aortic valve and aortic root pathologies.",signatures:"Ziv Beckerman and Edward P. Chen",downloadPdfUrl:"/chapter/pdf-download/60248",previewPdfUrl:"/chapter/pdf-preview/60248",authors:[{id:"65539",title:"Dr.",name:"Edward",surname:"Chen",slug:"edward-chen",fullName:"Edward Chen"},{id:"234157",title:"Dr.",name:"Ziv",surname:"Beckerman",slug:"ziv-beckerman",fullName:"Ziv Beckerman"}],corrections:null},{id:"61991",title:"Ebstein’s Anomaly",doi:"10.5772/intechopen.78067",slug:"ebstein-s-anomaly",totalDownloads:1988,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Ebstein’s anomaly (EA), a rare congenital heart disease, results from the failure of delamination of tricuspid valve (TV) leaflets from the endocardium of the right ventricle (RV) and apical displacement, particularly of the septal and posterior leaflets of TV. The most commonly accompanying cardiac malformation is atrial septal defect. Most EA cases are sporadic; familial ones are rare. EA patients may present at any age. Symptoms result from TV regurgitation, RV dysfunction, inadequate left ventricular filling owing to ventricular septal bowing, inadequate pulmonary flow, and arrhythmias. Atrial tachyarrhythmias are the most common late complications. There have been more techniques of tricuspid repair reported in the literature than any other congenital or acquired cardiac lesion. Neonatal operation has a higher risk of mortality than the operations performed beyond infancy. Late survival rate and the quality of life for hospital survivors are excellent.",signatures:"Sinem Altunyuva Usta, Ayşe Inci Yıldırım, Aysu Türkmen Karaağaç\nand Kaan Kirali",downloadPdfUrl:"/chapter/pdf-download/61991",previewPdfUrl:"/chapter/pdf-preview/61991",authors:[{id:"33985",title:"Dr.",name:"Ayse",surname:"İnci Yıldırım",slug:"ayse-inci-yildirim",fullName:"Ayse İnci Yıldırım"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5425",title:"Cardiomyopathies",subtitle:"Types and Treatments",isOpenForSubmission:!1,hash:"28ee6943b6ea8cfb4dcb919a521ff051",slug:"cardiomyopathies-types-and-treatments",bookSignature:"Kaan Kirali",coverURL:"https://cdn.intechopen.com/books/images_new/5425.jpg",editedByType:"Edited by",editors:[{id:"155565",title:"Prof.",name:"Kaan",surname:"Kırali",slug:"kaan-kirali",fullName:"Kaan Kırali"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5434",title:"Aortic Aneurysm",subtitle:null,isOpenForSubmission:!1,hash:"1fe6fcf4165a7f7732d4eb9c6b7a90fd",slug:"aortic-aneurysm",bookSignature:"Kaan Kirali",coverURL:"https://cdn.intechopen.com/books/images_new/5434.jpg",editedByType:"Edited by",editors:[{id:"155565",title:"Prof.",name:"Kaan",surname:"Kırali",slug:"kaan-kirali",fullName:"Kaan Kırali"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4642",title:"Coronary Artery Disease",subtitle:"Assessment, Surgery, Prevention",isOpenForSubmission:!1,hash:"7e46bbc1fe5312d5ccc58c3388a090aa",slug:"coronary-artery-disease-assessment-surgery-prevention",bookSignature:"Kaan Kirali",coverURL:"https://cdn.intechopen.com/books/images_new/4642.jpg",editedByType:"Edited by",editors:[{id:"155565",title:"Prof.",name:"Kaan",surname:"Kırali",slug:"kaan-kirali",fullName:"Kaan Kırali"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6209",title:"Endothelial Dysfunction",subtitle:"Old Concepts and New Challenges",isOpenForSubmission:!1,hash:"f6e76bbf7858977527679a6e6ad6a173",slug:"endothelial-dysfunction-old-concepts-and-new-challenges",bookSignature:"Helena Lenasi",coverURL:"https://cdn.intechopen.com/books/images_new/6209.jpg",editedByType:"Edited by",editors:[{id:"68746",title:"Dr.",name:"Helena",surname:"Lenasi",slug:"helena-lenasi",fullName:"Helena Lenasi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7220",title:"Congenital Heart Disease",subtitle:null,isOpenForSubmission:!1,hash:"f59bacfffcccc636ec3082869d10a82e",slug:"congenital-heart-disease",bookSignature:"David C. 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\r\n\tMalaria is an acute febrile illness caused by Plasmodium parasites, which are spread to people through the bites of infected female Anopheles mosquitoes. It’s the second commonest infectious disease worldwide (following hepatitis B). Despite being potentially preventable and curable, in 2020 there were an estimated 241 million cases; the estimated number of deaths being 627,000. Nearly half of the world's population is at risk of malaria. However, some population groups are at considerably higher risk of contracting malaria and developing the severe disease: children, pregnant women, and patients with low immunity. Noteworthy, 95% of malaria cases and 96% of malaria deaths occur in African Countries, with 80% of all deaths being in children under 5. Recent advancements include more accurate vectors control, chemotherapies, and possibly vaccine development. In this book, the current and most advanced knowledge about malaria is discussed, by focusing on pathobiology, diagnosis, clinical features, and management.
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In 2018, he was appointed for teaching at the Queen Mary University of London and Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya. He is the author of several international publications in journals such as Nature Medicine, Journal of Clinical Investigation, Journal of Experimental Medicine, Journal of Clinical Oncology, Blood, Lancet Oncology, and Lancet Infectious Diseases. 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Heat, in turn, produces work, e.g., in the form of electric energy in the so-called heat engines. It is the well-known fact that the efficiency of heat engines is restricted by Carnot principle. Therefore, it is generally recognized that heat cannot be fully converted to work. The efficiency of electric energy production due to the burning of fossil fuel of various kinds varies from 30 to 50 %.
On the other hand, there are galvanic and fuel cells whose efficiency can reach theoretically unity if it implies the ratio between the electric energy produced and the value of a change in Gibbs energy during chemical reactions occurring in a cell. These devices operate at constant temperature and pressure. It is concluded then that the devices, similar to a galvanic cell, cannot work at constant and uniform temperature according to the principle of heat engine. These devices assumed to operate only due to the direct transformation of chemical reaction energy, described by a change in the Gibbs energy, into work [1]. This viewpoint causes, however, numerous contradictions. The goal of this work is to analyze in detail the mechanism of useful work and heat production in chemical systems functioning at constant temperature and pressure.
In this Section, the fundamental functions of thermodynamics will be characterized, as the fundamental functions play the important role in the description of the process of the energy transformation. This notion includes four functions, i.e., internal energy, enthalpy, Helmholtz energy, and Gibbs energy. All of them are the state functions of energy dimension. It is generally believed that the value with energy dimension describes energy but this is by no means always the case. Below, the fundamental functions will elucidate whether these are energy values or not.
According to IUPAC [2], "
According to IUPAC, "
According to IUPAC, "
where
If the process occurs at constant volume, the expansion work is absent and
Thus, eq. (1) is of the form in the case of reversible process
where
According to IUPAC [2], "
where
Unfortunately, the word "energy" as defined by IUPAC for a Gibbs energy (and also for a Helmholtz energy), causes great confusion. The Gibbs energy
Consider now the problem of
Let us consider another example. Let the ideal gas-phase system involves a spontaneous process of the monomolecular transformation of substance A into B. As suggested a change in enthalpy tends to zero in this reaction. Thus, the internal energy, temperature, pressure, and volume will not undergo changes in this process. However, the entropy will increase due to the entropy of the mixing, because the entropy is a function of state. The value of the
Since neither enthalpy nor
Nevertheless, the notions that the Gibbs energy is the energy and thus, obeys conservation laws, prove to be long-lived, which causes erroneous interpretation of a number of processes some of which are of paramount importance.
Let us consider now the reaction of adenosine triphosphate (ATP) hydrolysis in water solution which is of great concern in biochemistry
ATP + H2O = ADP + Pi.
Under the standard conditions [6]
The heat of 4 kcal mol-1 is actually released into solution due to hydrolysis. Unfortunately, it is then assumed that the Gibbs energy is conserved which makes his difference in
Thus, among the four quantities, that claims to be called energy quantity, only the internal energy deserves this name. The other functions, i.e., enthalpy
This Section is devoted to the discussion of the generally accepted theory of the direct conversion of energy [1, 8] produced by chemical reaction to useful work. For simplicity, hereafter exergonic
The useful work of the chemical reaction occurring at constant temperature and pressure in the reversible conditions can be calculated through the change in the Gibbs function (5). When the interest is the useful work performed by the system in the environment
From eq. (6) it follows formally that the useful work of the reversible system in the environment is the sum of the enthalpy member
Fromeq. (6) it follows, that for
The second case of
The third case is
In the fourth case
As mentioned in the Introduction, at present, it is generally accepted that the high efficiency of reversible devices is inconsistent with the notions that heat can be used to produce work and that such devices realize the direct conversion of chemical system energy into work. But below it will be shown that in all the cases, the useful work results from the heat of volume
In this Section, it will demonstrate the mechanism of producing useful reversible work which involves no notions of the direct conversion of reaction energy into useful work. To this end, let us consider a Van’t Hoff equilibrium box (VHEB) [9 – 11]. A thermodynamic system must provide realization of the reversible process. This means that all changes in the system are infinitely slow at infinitely minor deviation from equilibrium.
It is assumed that in the system the following reaction occurs
where
Production of useful work and heat in a closed reversible system. Ast (Bst) indicate the reagents A
Let us consider reversible chemical process in a closed system (Fig. 1). The realization of the reversible chemical process consists in reversible transformation of the reagents to products via chemical reaction. Let us consider the closed system.
The process of reversible work production includes six stages.
A small amount of substance A
Then, the change in the Gibbs function and the work are zero
Reagent A
where
The thermostat enthalpy varies as follows:
Reagent A
The useful work production and the change in thermostat enthalpy
where
The same procedure is used to bring products from the standard vessels to reactor.
An equivalent amount of product B
Product B
Product B
The change in the thermostat enthalpy upon thermal energy conversion into useful work at step 5 is
where and
The change in the thermostat enthalpy at the second and fifth steps obeys the equation
where
For the reversible process, the maximal useful work is numerically equal to
The process has resulted in the useful work of the reaction,
Thus, the mixture in the reactor is moved off balance to be restored later. As a result, the reaction heat is emitted into the thermostat. Indeed, because of the elementary chemical act in the reactor, the energy released concentrates at the degrees of freedom of the product molecules. As the reactor temperature is constant, this energy is dissipated in the reactor and transferred to the thermostat which causes a
The cycle is over. Equations (12, 13) can be used to calculate the total change in thermostat enthalpy
The change in thermostat enthalpy is controlled only by reaction entropy [11].
This consideration demonstrates the main characteristics of the reversible process of useful work production at constant temperature and pressure in closed systems:
The useful work arises from the stage of the reversible transport of reagents from reservoir to reactor and from the stage of the reversible transport of products from the reactor.
The only energy source of useful work is the thermal energy of thermostat (or environment).
The heat released by chemical reactions is dissipated to the thermostat; the reaction heat is infinitely small in comparison with the volume of the thermostat thermal energy; therefore no reaction heat is really needed to produce work.
Although the useful work is produced by the cooling of one body (thermostat), the second law of thermodynamics is not violated, because the process is followed by a change in the amount of reagents and products.
The useful work is produced by heat exchange with thermostat (environment) according to the scheme
reaction heat → thermal thermostat energy → useful work(scheme I)
The maximal useful work is equal the heat dragged by tools from thermostat.
Useful work depends on the difference in the concentrations of standard and equilibrium states of reagents and products. Therefore, the amount of extracted energy can be calculated via the change in the Gibbs function.
There is no direct conversion of the Gibbs energy into useful work. Gibbs energy is equal numerically the thermal energy dragged by systems from the environment for doing work.
Usually, the total energy which can be produced by chemical system, is
The open system is depicted in Fig. 2. As compared with the closed one (Fig. 1), the open system consists of two thermostats: the first one contains a reactor and the second one contains standard vessels with substances A and B and tools. The second thermostat can be replaced by the environment. In the process, steps 1, 2, 5, and 6 occur in the second thermostat (environment); steps 3 and 4 take place in the first one. Thus, the heat is released in the first thermostat only and the work is performed by thermal energy of the second thermostat (environment). The processes of heat and work production are spatially separated! The energy potential of the open system obeys the equation
Production of useful work and heat in the open reversible system. The designations see in the subscription to
In the case of coal burning, it is possible to obtain the double total energy [11]. Thus, understanding the mechanism of useful work production in the reversible process allows us to predict an increase in the energy potential of chemical reactions in the open system.
It is worth noting that the open system under study is not a heat pump. The heat pump consumes energy to transfer heat from a cold body to the warm one. The open system studied does not consume external energy and produces heat due to chemical reactions in one thermostat and performs work by extraction of thermal energy from the second one.
The chemical reaction heat is always released in the reversible chemical processes and passes to the environment independent of the fact whether the system produces work or not, whether it is closed or open. The discussed mechanism of useful work production in the reversible systems did not use such notions as "free energy", "bound energy", "direct Gibbs energy conversion". The useful work arises only due to the heat exchange with a thermal basin in the process, described by the scheme I. The total energy of chemical system can be high and equal to
The current theory of galvanic cells [1, 3, 8] is based on a direct transformation of the energy (
The mechanism of electric energy production in galvanic cells will be solved by analyzing the behavior of one ion. But it does not denote that thermodynamics will be applied to a real single ion: thermodynamic parameters of one ion imply the averaged parameters of many ions.
For simplicity a Daniell cell will be considered, consisting of zinc (№1) and copper (№2) electrodes (Fig. 3). The activity of salts in solutions is denoted by
where
where
which readily gives the expression for both the work performed on the first electrode and its galvanic potential [3]
The latter is the potential for a half-cell. Thus, the approach, based on the consideration of the behavior of one ion, provides a common expression for electrode potential.
Establishment of equilibrium on the electrodes
The change in electrode enthalpy involves dissolution enthalpy and thermal energy consumption upon ion transport into solution. The equation for dissolution enthalpy is readily obtained from eq. (16)
where
where
As follows from eq. (22), the change in enthalpy, related to the first electrode, is independent of the processes, occurring on the second one. Therefore, studying either release or absorption of heat on a separate electrode, one may calculate the change in entropy due to the escape of the ions of the same type into the bulk.
A corresponding expression for the second electrode is of the same form but index "1" should be substituted by index "2":
In the operation of the galvanic cell, the processes on the second electrode are oppositely directed which should be taken into account in consideration of the thermodynamic cell parameters.
Equations (20) and (26) allow to get the Nernst equation for the potential of the cell [3]
where
The electric work of the galvanic cell (
The change in thermostat enthalpy is of the form
which is in fair agreement with similar expression, described by eq. (14), for the VHEB. The detailed equation for
The sum of eqs. (31) and (33) gives the total energy (electric work + heat), produced by the galvanic cell
From eq.(34) it follows that the total energy produced by the galvanic cell is equal to the heat emitted by oxidation-reduction reaction.
Thus, the approach, based on the analysis of the behavior of one ion gives the same results as the present-day theory. However, it uses not a mysterious, direct transformation of the chemical energy (
reaction heat → thermal thermostat energy → potential energy of charged electrodes → electric energy.
Thus, in various systems with uniform temperature, useful work is produced by the same mechanism through the exchange of thermal energy with thermostat (environment). No direct conversion of chemical energy into useful work is observed. Unfortunately, in the galvanic cell, the processes of heat release and useful work production cannot be spatially separated, because both of them occur in a double layer. Therefore, galvanic cells are unpromising in production of a double amount of energy.
Consider now a concentration cell, consisting of two electrodes, e.g., the zinc ones of different solution activity. Standard changes in the Gibbs function, enthalpy, and entropy for the concentration cell tend to zero due to the same chemical nature of both of the electrodes. By definition, it has been considered that
which is a usual expression for the electric energy of the concentration cell. From eq. (34) it follows
For the system in which the activities are temperature-independent, the electric energy arises from the thermal thermostat energy (environment)
which is in fair agreement with conventional concepts.
An ideal system with concentration gradient has no potential energy because the mixing does not result in heat release and
The useful work of the system with a concentration gradient
Any non-equilibrium state can serve as an energy source. The thermostat (environment) is an active participant of the process of reversible useful work production in devices operating at constant temperature. The heat released by chemical reactions, always dissipates in the thermostat (environment). The useful work is produced by special tools that provide the extraction of the thermal energy of the thermostat (environment) and the transformation of thermal energy into work at the process of the restoration of the chemical equilibrium. The volume of the useful work is equal, in reversible conditions, to the change in Gibbs function. A spatial separation of reactor and tools can lead to a substantial increase in the energy produced. The direct conversion of the Gibbs energy into useful work does not exist. The concepts of free and bound energy become unnecessary.
Tissue engineering advanced from the field of biomaterials development and denotes the practice of combining cells, tissue scaffolds, and bioactive signal molecules. These tissue scaffolds are produced by various decellularization processes, such as chemical and physical methods. Tissue scaffolds, cells, and biologically active signal molecules are the three key elements for tissue and organ reparation. Tissue engineering is defined as “
Tissue engineering and regenerative medicine (TERM) have been projected and established for almost 30 years. Though many fruitful challenges in tissue regeneration have been attained, TERM is still in its infancy stage and most of the vital questions remain to be answered, including the selection of cell sources, development of tissue-specific materials, and construction of complex organs. The most important is the
Tissue and organ repair remain a clinical issue and challenge. Entirely restoring or regenerating damaged tissues and organs and reestablishing their functions have been a vision of medical society. The emergence of tissue engineering and regenerative medicine (TERM) makes it possible. TERM is a developing field that focuses on the advancement of alternative therapies for tissue and organ restoration [2, 3]. TERM is an extremely multidisciplinary arena, in which bioengineering and medicine unite. It is constructed on integrative approaches using scaffolds, cells, growth factors, nanomedicine, and other techniques to pass on the restrictions that presently exist in the hospitals. Certainly, TERM overall aim is to encourage the formation of new functional tissues, rather than just implanting tissue and bone parts [2]. TERM is a multifaceted science and associates basic sciences such as materials science, biomechanics, cell biology, and medical sciences to comprehend functional tissue and organ restoration and reconstruction. The world’s population is aging and the trend is escalating. There is a severe global shortage of tissues and organs for transplantation. TERM has the potential to meet the requirements of the forthcoming needs of patients [2, 4]. TERM aims to create a three-dimensional (3D) cell-biomaterial composite, that possesses a comparable function as living tissue and organ and is employed to restore or regenerate damaged tissue and organ. The basic condition for the 3D composite is to support cell growth, nutrition and waste transport and gas exchange. TERM typically employs the following strategies, cell-biomaterial composite, in which cell-seeded biomaterials are implanted into the body to restore and regenerate tissues and organs; stem cell transplantation; and biomaterial implanted into the body and undertake the process of tissue integration [3]. Scaffolds are vital for tissue engineering approaches for several reasons; as a three-dimensional structure, they offer volume fill, mechanical integrity and a surface that can afford chemical and architectural guidance for regenerating tissues [5]. The three vital elements in TERM are cells, scaffolds and signals (Figure 1). Several decellularization techniques had been used for the production of collagen scaffolds for TERM application, including the supercritical carbon dioxide (SCCO2) extraction technology to be discussed here in this article.
The triad of TERM.
Collagen-based biomaterial application in the field of TERM has been significantly increasing over the past decades. Collagen owns the main advantages as it is biodegradable, biocompatible, easily available and highly versatile. However, collagen is a protein, therefore it is problematic to sterilize without altering its native structure. Collagen-based biomaterials developed for TERM were intended to provide a functional biomaterial for use in TERM from the laboratory bench to the patient bedside [6]. Collagen is present in all connective tissue and makes it one of the most studied biomolecules of the extracellular matrix (ECM). It is the major component of skin and bone and constitutes approximately 25–35% of mammalian total dry weight [7]. Until now, 29 diverse collagen genotypes have been characterized and all depict a typical triple helix structure. Fiber form of collagens are types I, II, III, V and XI. Collagen molecules are made up of three α chains that assemble due to their molecular structure. Each α chain is made up of more than a 1000 amino acids based on the repeated sequence -Gly-X-Y-. The vital part is the presence of glycine at every third amino acid position to permit for a tight triple-helical packaging of the three α polypeptide chains. In the tropocollagen molecule the X and Y positions are mostly filled by proline and 4-hydroxyproline [6, 7]. Though numerous types of collagens (Table 1) have been defined, only a few types are used to yield collagen-based biomaterials. Currently, type I collagen is the gold standard in the field of TERM.
I | [α1(I)]2α2(I) | Fibril | Bone, skin, tendons, ligaments, cornea |
II | [α1(II)]3 | Fibril | Cartilage, intervertebral disc, notochord, vitreous humor in the eye |
III | [α1(III)]3 | Fibril | Skin, blood vessels |
V | [α1(V)]2α2(V) and α1(V)α2(V)α3(V) | Fibril (assemble with type I) | |
XI | α1(XI)α2(XI)α3(XI) | Fibril (assemble with type II) | |
IX | α1(IX)α2(IX)α3(IX) | Lateral association with type II fibril | Cartilage |
XII | [α1(XII)]3 | Lateral association with type I fibril | Tendons, ligaments |
IV | [α1(IV)]2α2(IV) | Sheet-like network | Basal lamina |
VII | [α1(VII)]3 | Anchoring fibrils | Beneath stratified squamous epithelia |
Collagen types, forms and distribution [6].
Medical application of collagen biomaterial needs to make a clear difference between immunogenicity and antigenicity. Immunogenicity is triggering an immune response; however, antigenicity denotes the interaction between the antibodies and the antigenic epitopes. Collagen mediated immune response primarily targets epitopes in the telopeptide region at each end of the tropocollagen molecule. The polymerized collagen fibrils conformity of the helical part and the amino acid sequence on the surface can influence the immunologic profile of the collagen molecule [7]. Type I collagen is an appropriate biomaterial for implantation meanwhile only an insignificant number of people have humoral immunity against type I collagen. In addition, a simple serologic test can validate an allergic reaction in response to type I collagen-based biomaterial. It is most crucial to discuss that collagen immunogenicity which is relevant to collagen molecules that are made up of an acellular ECM and the utmost adverse immune responses that have been come across with an acellular scaffold are not necessarily initiated from the collagen molecule itself. Incomplete decellularization with the presence of remaining oligosaccharide α-Gal and DNA is the common reason for acute immune responses and subsequent acellular ECM rejection [7, 8].
The traditional decellularization techniques involve long duration and increased cost as well as long-term washing of the tissue material from the residual and traces of the chemicals used. Despite the numerous decellularization process that exists, it is necessary to go through a lot of parameters for multiple reasons in the decellularization process (Table 2). The decellularization process aims to remove the cellular material of the donor, antigens, and potential pathogens. In addition, the most critical issue is to offer the conservation of the structural organization of an ECM with the set of functions inherent in it. Therefore, the optimization of these decellularization methods and the pursuit of improved methods are still ongoing [9]. At present, numerous procedures for decellularization of tissues were employed that include the treatment by detergents such as sodium dodecyl sulfate (SDS), sodium deoxycholate, Triton X-100, etc., and treatment by enzymes such as trypsin, deoxyribonuclease (DNase), and ribonuclease (RNase). Other methods include alkali treatment, as well as cyclic freezing-thawing and high-pressure action up to 1 GPa, which have been tried (Table 3) [9, 10].
Supercritical phase pressure disrupts ECM. Uses inert gas (CO2) for cell removal and do not alter ECM’s mechanical properties | No known disadvantages. Not yet widely employed for decellularization | |
Disinfects material by entering inside microorganisms and oxidizing enzymes | Dissociate important molecules in ECM including GAGs, from collagen scaffold | |
Better preservation of GAG content | Disruptive to elastin and collagen and elicits immune response | |
Preserves protein-protein interactions intact and retains sulphated GAG content | Disrupts ECM ultrastructure and owers laminins/fibronectin content | |
Effectively removes cells from the tissue | Disrupts protein-protein interactions and causes a decrease in GAG content and collagen integrity | |
Preserves native ECM | A high degree of protein denaturation | |
No advantages | Crosslinks and precipitates proteins, including collagen | |
Effective cell removal | Parameters are not well standardized | |
Effective cell removal | Ineffective for densely organized ECM tissues |
Decellularization techniques used for tissues, organs and their advantages and disadvantages.
Bone regeneration | Development of a decellularized porcine bone graft by supercritical carbon dioxide extraction technology for bone regeneration. | Chen et al. [23] | Production and evaluation of biocompatibility of bone graft |
Skin regeneration | Regenerative porcine dermal collagen matrix developed by supercritical carbon dioxide extraction technology: Role in accelerated wound healing. | Wang et al. [33] | Wound healing, skin graft and regeneration |
Skincare industry and medical applications | Protocols for accelerated production and purification of collagen scaffold and atelocollagen from animal tissues. | Hsieh & Srinivasan [34] | Accelerated production and purification of atelocollagen |
Experimental and clinical tissue regeneration | Protocols for the preparation and characterization of decellularized tissue and organ scaffolds for tissue engineering. | Hsieh et al. [16] | Preparation and characterization of decellularized tissue and organ scaffolds |
Wound healing | Supercritical carbon dioxide-decellularized porcine acellular dermal matrix combined with autologous adipose-derived stem cells: Its role in accelerated diabetic wound healing. | Chou et al. [35] | Accelerated diabetic wound healing |
Extraction socket bone regeneration | Evaluating the bone-regenerative role of the decellularized porcine bone xenograft in a canine extraction socket model. | Chen et al. [36] | Guided bone regeneration, extraction socket bone regeneration |
Corneal replacement | Preparation of acellular scaffold for corneal tissue engineering by supercritical carbon dioxide extraction technology. | Huang et al. [37] | Production and evaluation of biocompatibility of acellular corneal scaffold |
Bone regeneration | Reconstruction of the orbital floor using supercritical CO2 decellularized porcine bone graft. | Huang et al. [38] | Orbital floor reconstruction |
Corneal transplantation | Acellular porcine cornea produced by supercritical carbon dioxide extraction: A potential substitute for human corneal regeneration. | Liang et al. [39] | Biocompatibility of acellular corneal scaffold in rabbit lamellar corneal transplantation. Potential substitute for human-donated cornea for corneal transplantation |
Bone regeneration | Supercritical carbon dioxide decellularized bone matrix seeded with adipose-derived mesenchymal stem cells accelerated bone regeneration. | Liu et al. [40] | Accelerated bone regeneration |
Rhinoplasty | A novel 3D histotypic cartilage construct engineered by supercritical carbon dioxide decellularized porcine nasal cartilage graft and chondrocytes exhibited chondrogenic capability | Lee et al. [27] | Engineered 3D histotypic cartilage construct for nasal septum reconstruction |
Osteoarthritis | Supercritical carbon dioxide decellularized porcine cartilage graft with PRP attenuated OA progression and regenerated articular cartilage in ACLT-induced OA rats. | Wu et al. [41] | Repair and regeneration articular cartilage in osteoarthritis |
Osteoarthritis | 3D composite engineered using supercritical CO2 decellularized porcine cartilage scaffold, chondrocytes, and PRP: Role in articular cartilage regeneration. | Chen et al. [30] | 3D composite engineered decellularized porcine cartilage scaffold in articular cartilage regeneration |
Porcine tissues and organs had been decellularized by the SCCO2 process applied in different medical applications.
Currently, the most frequently employed decellularization technique for tissue and organ to manufacture scaffolds employing detergents are sodium dodecyl sulfate, Triton X-100, and CHAPS, branded as ionic, non-ionic, and zwitterionic detergents, respectively. Detergents were found to be effective in the decellularization of the tissues and organs, including the removal of lipids [11, 12]. Enzymes such as nucleases are also employed in limited decellularization protocols to eliminate the DNA from the tissues and organs [12, 13]. However, detergent-employed decellularization often disrupts the ECM by changing tertiary and quaternary structures of the proteins. SDS is known to proficiently eliminate glycosaminoglycans, thereby destructing the collagen structure [14]. Detergent decellularization is known to reduce the number of valuable growth factors that are vital for the recellularization of tissues. Moreover, residual surfactants and chemicals often cause cytotoxicity [15] inducing adverse effects in the recellularization of tissue and organ scaffolds (Table 3) [13, 14, 16].
Common traditional decellularization methods for adipose tissue include numerous freezing-thawing cycles, extraction of lipids with isopropanol, and enzymatic treatment. Developing a protocol for the preparation of ECM from adipose tissue in an accessible and eco-friendly manner will promote the upgrading of the methods of tissue engineering with the use of autologous material [9, 14, 17, 18, 19].
The existing techniques for pericardium decellularization include the treatment by non-ionic detergents such as Triton X-100, 3-3-chloroamidopropyl-dimethylammonio-1-propanesulfonate (CHAPS), ionic detergents (SDS), sodium deoxycholate, alkalis, and enzymes such as trypsin with EDTA. However, the adverse effects are commonly occurred by the above-mentioned procedures on the ECM structure and composition. The detergents such as SDS and Triton X-100 were found to denature the collagen of the ECM which was elucidated by staining fluorescently labeled collagen hybridizing peptide. CHAPS and sodium deoxycholate altered the structural organization of collagen established by the recording of the second harmonic signal and transmission electron microscopy. Decellularization of bovine pericardium tissue using Triton X-100 reduces the concentration of glycosaminoglycans by ~62–66%, and in an alkaline solution, by ~88.6%, at the initial concentration of ~0.6 mg/g [9, 14, 17, 18, 19].
The current standard method employed for bone decellularization is by high-temperature sintering at 300–1300°C. Moreover, this procedure completely removes any possible zoonotic infectious agents, in addition to the immunogenic components that existed in the animal bone tissues [20]. However, the high-temperature sintering damages the intrinsic collagen and alters the porous ECM structures of the animal bones. Bone decellularization can also be carried out by various chemical agents and techniques. The chemical process includes processing the bone with acidic and alkaline solutions and organic agents, as well as detergents and enzymes, that unavoidably alter the ECM structure. Delipidation is the key factor in decellularization processing because indisputably, the residual lipids in the bone act as a barrier to cell removal, in addition to altering its biocompatibility and osseointegration [21]. Moreover, it encourages adverse reactions which can give rise to bone resorption and encapsulate fibrosis [22, 23].
Decellularization of cartilage is challenging, due to its dense structure with lacunae. Generally, decellularization of cartilage is performed by the perfusion of detergents into the lacunae to break down the chondrocytes. In continuation, the detergents were washed out of the residual cellular fragments and nucleic acids. In another case, decellularization of cartilage was performed by treating with 0.05% Trypsin/EDTA for 1 day followed by 3% SDS for 2 days and 3% Triton X-100 for another 2 days [24]. Decellularization of the cartilage process includes a mixture of physical, chemical, and enzymatic steps [24]. Decellularization of cartilage by SDS and Triton X-10 resulted in only a 77% decrease in DNA content (262 ± 42 ng/mg) relative to the untreated cartilage. But, the key norms for medical devices, the decellularized tissue residual DNA content should be less than 50 ng/mg in decellularized materials. However, the dense nature of the cartilages reticular network of fibrous ECM is a substantial barrier for the detergents to penetrate. It is the key limitation of SDS and Triton X-100 in cartilage decellularization [24, 25]. Cartilage complete decellularization by SDS (2%) treatment for 4 or 8 h; however, 60% of the DNA remained in the decellularized cartilage [26, 27]. Decellularization of cartilage by using 1% SDS for 24 h and 2% Triton X-100 for 48 h preserved most of the ECM components with a complete chondrocyte’s removal. The complete decellularization of chondrocytes and the movement of seeded cells into the scaffolds during recellularization is challenging. The decellularization process in the SDS process caused the denaturation of proteins in ECM structures, which may also destroy the protein function [27, 28]. Cartilage decellularization methods such as chemical and enzymatic methods lead to disadvantages including traces of impurities and loss of ECM scaffold structure caused by the degradation of native collagen ECM structure leading to difficulty in the recellularization of the cartilage scaffold. Porcine articular cartilage decellularized by a succession of freeze-thaw cycles and 0.1–0.5% (w/v) sodium dodecyl sulfate detergent cycles with chondroitinase ABC and hyaluronidase were employed to breakdown glycosaminoglycans, resulting in the removal of 80–90% of the DNA [29, 30].
The conditions necessary for the decellularization processing of biomaterials frequently reject the use of traditional approaches involving destructive action on the biomaterial such as high-temperature treatment, acid, and alkali, etc. A result of the search for an alternative process leads to novel processing technologies and approaches concentrating on the direction of green technology in the first place. Supercritical carbon dioxide extraction technology comes in the first place in green technology. Supercritical carbon dioxide extraction technology owns exceptional advantages that can be employed in the production of biomaterials efficiently and cost-effectively. The most vital and important advantage of SCCO2 is the option of conducting processes at low temperatures, which offers the opportunity to work with a variety of biomaterials and thermally sensitive components such as collagen [31]. In the SCCO2 process, the low surface tension encourages the penetration of CO2 into solid and colloidal structures, which makes it competently decellularize and sterilize biomaterial and medical devices with the preservation of the structure and physicochemical properties (Table 4) [32].
Supercritical carbon dioxide extraction technology | Bone, skin, cornea, cartilage, nerve, tendons, artery, pericardium, aortic-pulmonary valve, heart, liver, kidney, pancreas |
Non-ionic detergents (Triton X-100) | Subcutaneous adipose tissue, myocardium, pericardium, aortic-pulmonary valve, gingiva, dental pulp, bone, skin, cornea, cartilage, artery, tendon, liver, kidney, pancreas |
Ionic detergents (sodium dodecyl sulphate (SDS)) | Muscle, tendons, adipose tissue, heart, pericardium, valves, artery, liver, kidney, testis, ovary, placentam, cornea |
Zwitterionic detergents (CHAPS) | Arteries, lung, heart, esophagus, cornea, nerve, liver |
Sonication | Cartilage, kidney, artery, larynx, meniscus, trachea, aorta, nerve, cornea, osteochondral tissue, meniscus, intervertebral disc, adipose tissue, heart |
High-pressure gradient system | Artery, soft tissue, heart tissue, cornea, aorta, kidney, pericardium, bone matrix |
Enzymes | Cornea, amniotic membrane, pancreas, tracheal cartilage, atery, dermis, tendon, larynx, nerve, heart values, umblical cord artery, amniotic membrane, aorta, muscle |
Solvents | Cornea, placenta, kidney, liver, dental pulp, heart, dermis |
Decellularization techniques are used for tissues and organs.
In the supercritical process, the carbon dioxide gas above a critical temperature, Tc = 31.1° C, and pressure, Pc = 73.8 bar is said to be supercritical (Figure 2). In this state, carbon dioxide is neither a gas nor a liquid but possesses properties of both. The critical state of carbon dioxide is established by the phase diagram in Figure 2; varying the temperature and pressure changes the phase from solid to liquid to gas. However, at the critical point (the intersection of Tc and Pc), the difference between the liquid and gas phases disappears. The single fluid phase of carbon dioxide at this point is supposed to be “supercritical”. The decellularization of mammalian tissues was successfully carried out using the extractive properties of SCCO2 technology (Figure 3). To eliminate the immunogenicity of xenogeneic and allogeneic tissues requires decellularization. The decellularization process of the tissues to ECM scaffolds is to remove cells and antigens from the source tissue material. The ECM scaffold developed as an outcome of the decellularization process is the ECM consisting of proteins such as collagen, laminin, elastin, proteoglycans, and glycoproteins, as well as essential growth factors, angiogenesis factors [11]. Many porcine tissues and organs had been decellularized by the SCCO2 process (Figures 3 and 4) and had been applied in several different medical applications by our team as listed in Table 5.
Phase diagram of CO2.
Production of collagen scaffolds by SCCO2 technology.
Natural collagen scaffolds prepared by SCCO2 technology.
Princple | The carbon dioxide gas above a critical temperature, Tc = 31.1° C and pressure, Pc = 73.8 bar is said to be supercritical. In this state, carbon dioxide is neither a gas nor a liquid but possess properties of both. At the critical point, the difference between the liquid and gas phases disappears. The single fluid phase of carbon dioxide at this point is supposed to be ‘supercritical’. This supercritical liquid can penetrate the tissue and organs efficiently to break down cellular components, which are washed off, with unaltered ECM scaffold. |
Advantages | Green technology, cost-effectively, low temperatures, non-flammable, easily available, non-toxic, non-explosive, no chemical traces, no organic solvent, low viscosity, low surface tension, high density, gentle treatment, high productivity, fast and efficient, continuous and automatic with very low idle and turnaround time, non-corrosive, odorless, colorless. “Generally Regarded as Safe”. |
Disadvantages | No known disadvantages related to tissue decellularization. However, expensive equipment and the analysis process. Operated at the high pressure 1000–5000 psi. |
Applications | Organ snd tissue decellularization, which can be used as a “high end medical devises”. |
Supercritical carbon dioxides principle, advantages, disadvantages and applications.
The first effort for the decellularization of the porcine aorta employing SCCO2 with the cosolvent as absolute ethanol was reported in 2008 [42]. The structural analysis depicted that the addition of ethanol encourages the removal of cellular material such as nuclei and phospholipids, which was unattainable without the use of SCCO2 as a cosolvent. The results showed a decrease in the amount of phospholipids which depends on the time of processing, pressure, and rate of venting in the reactor. Altering the conditions, the lowest residual amount of phospholipids was 20%, which was attained as a result of 20 min at 15 MPa and 37°C. During the progression SCCO2 process with the ethanol system, the aorta obtains rigidity, which reflects upon the character of the stress-strain diagrams. It is related to the dehydration of the aorta tissue due to the hygroscopic nature of ethanol and SCCO2 dissolves up to 0.5% water [43]. The insignificant changes in mechanical properties and the deviations are not functionally significant [42]. This is the basics in the field of SCCO2 decellularization; however, this process was not continued, due to the fast progress of methods of decellularization using detergents, enzymes, and other physicochemical methods. The preparation of biomaterials using SCCO2 was resumed due to renovating the interest in solving the problems of decellularization and the factors such as the growth of new instrumentation, transition to green chemistry.
In the SCCO2 decellularization process, the native collagen scaffold remains completely intact, even the smallest of the collagen strand (Figure 5, dermis ECM) as shown in the scanning electron microscopic photos of several different porcine tissues and organs. Therefore, we believe SCCO2 decellularization is superior to other decellularization processes and thus the holy grail technology for the preparation of collagen scaffolds for tissue engineering and regenerative medicine. The process of decellularization of the aorta by SCCO2 was continued in 2017 by altering the protocol using 70% ethanol and the processing was executed for 1 h at 37°C in addition 17.2 and 31 Mpa [44]. The results of histological studies and residual DNA exhibited complete elimination of the cellular debris from the aorta tissue is accomplished at 31 MPa. However, the ECM structure of the aorta is significantly altered at higher pressure, and the organization of the layers of the aorta external and internal layers is altered. These alterations in the aorta are capable of encouraging the development of embolism and aneurism in the case of grafting, which is a severe constraint for the clinical use of the aorta graft. In addition, these alterations of the aorta structure change the mechanical properties of an ECM.
Porcine bone derived products.
To treat ischemic diseases, cardiac tissues were decellularized using SCCO2with a cosolvent of absolute ethanol, leading to the formation of a hydrogel-based on an ECM, a source of glycosaminoglycans, proteins, and growth factors [13]. To attain the determined effect, the pressure was elevated to 35 MPa, and the time of the processing was extended to 6 h. The cardiac tissues were then rinsed in a solution of DNase I for 5 days. ECM components responsible for angiogenesis are preserved in the SCCO2 decellularization; however, 1% SDS altered the ECM. Upon subcutaneous implantation of the hydrogel to mice induced angiogenesis. Subsequently encouraged the development of vessels to a significantly superior extent in comparison with the SDS treated and control gel based on type I collagen. Therefore, decellularization using the SCCO2 opens up projections for the progression of bioinks for bioprinters and the formation of three-dimensional structures based on hydrogels [13].
The porcine cornea was decellularized by SCCO2 [45], the cornea tissue was initially subjected to osmotic shock by changing 2 M NaCl solution and deionized water. The process of SCCO2 was done with the cosolvent addition of 60% ethanol at 35 MPa and 45°C for 80 min. In this process, it is likely to eliminate cellular components from the corneal tissue with the conservation of the suitable optical properties of the cornea. However, the decrease in the quantity of glycosaminoglycans and structural proteins during the processing in SCCO2 directed to the alterations of the structural organization of the corneal ECM. In the traditional procedure decellularization by Triton X-100, the effect was less noticeable. The transplantation of the SCCO2 decellularized cornea to rabbits showed regeneration of the cornea in 2 months, which confirmed the migration of keratocytes and corneal epithelial cells to the implanted cornea. In addition, no adverse rejections, inflammation, or angiopoiesis was observed in the implanted cornea. For the first time, the results of the regeneration of corneal tissues with the use of SCCO2 decellularized transplants over the long term were described. The physical decellularization method of the cornea was established previously by the destruction of cells under the action of high pressure up to 100 MPa. However, the high-pressure method involves complex and costly hardware.
The SCCO2-decellularized corneas displayed intact stromal structures and appropriate mechanical properties and had biocompatibility. Additionally, no immunological reactions and neovascularization were observed after lamellar keratoplasty in rabbits without complications. The transplanted decellularized corneas became transparent within 2 weeks of surgery. The decellularized corneas were completely re-epithelialized within 4 weeks. In conclusion, SCCO2 decellularized corneas could be an ideal and useful scaffold for corneal tissue engineering [37]. The SCCO2 technology-mediated production of the acellular porcine cornea (APC) depicted complete cells and non-collagenous protein removal relative to the Triton-sodium dodecyl sulfate decellularization process. APC presented excellent biocompatibility in rabbit lamellar corneal transplantation with a follow-up to 1 year. APC can be a potential substitute for human-donated cornea for corneal transplantation in the near future [39].
Decellularized bone tissue matrix produced by SCCO2 [46], bovine cancellous bone was treated at 35 MPa and 50°C for 30 min with 25 min in a dynamic mode at a rate of the flow of SCCO2 of 16.9 g/min and 5 min in a static mode of supercritical process. Subsequently, bovine cancellous bone was treated with a 7% solution of NaCl for 12 h first and then in a 0.1% solution of H2O2 for 48 h. On comparing lipid removal in bovine cancellous bone by SCCO2 with traditional extraction with n-hexane in a Soxhlet apparatus, the SCCO2 removed lipids 14% more efficiently. The biocompatibility of the SCCO2 decellularized bone was proved by seeding and culturing with mesenchymal stem cells. However, mechanical properties and immunogenicity of the SCCO2 decellularized bone were not determined. Similarly, xenogeneic bone decellularization [47] by SCCO2 was done by rinsing with a 3% H2O2 solution and processing in the subcritical water, and final processing in SCCO2.
The SCCO2 technology was used to produce a series of novel decellularized porcine collagen bone grafts (DPB) in an assortment of shapes and sizes (Figure 5, cancellous bone). The native intact collagen was preserved in the SCCO2 processed DPB was confirmed by Masson trichrome staining. The cytotoxicity and biocompatibility tests according to ISO10993 and their efficacy for bone regeneration in osteochondral defects in rabbits were evaluated. The rabbit pyrogen test confirmed DPB was non-toxic.
The DPB produced by SCCO2 ABCcolla® Collagen Bone Graft, was used for the reconstruction of the orbital framework in humans. The orbital defects were fixed by the implantation of the ABCcolla® Collagen Bone Graft. All subjects showed improvement of enophthalmos on computerized tomography at week 8 follow-up. No replacement of implants was needed during follow-ups. Thus, ABCcolla® Collagen Bone Graft proved to be safe and effective in the reconstruction of the orbital floor with high accessibility, high stability, good biocompatibility, low infection rate, and low complication rate [38]. The DPB produced by SCCO2 seeded with adipose-derived stem cells (ASCs) boosted callus formation in a segmental femoral defect. The mechanism of DPB might be modulation in the expression of BMP 2 and osteocalcin, thus leading to enhanced bone regeneration and new bone formation in a rat segmental femoral defect model. Thus the DPB scaffold is an excellent biomaterial for bone tissue repair. Implantation of the DPB seeded ASCs stimulated endochondral ossification for substantial bone regeneration. The DPB seeded ASCs system is of clinical relevance for segmental defect bone regeneration [40].
The SCCO2 decellularized porcine acellular dermal matrix (ADM) seeded with autologous adipose-derived stem cells (ASCs) in streptozotocin (STZ)-induced diabetes mellitus rats showed the wound healing rate increased in diabetes mellitus. Diabetes mellitus wound treated with ADM-ASCs showed a significantly higher wound healing. ADM-ASC-treated rats showed significantly increased epidermal growth factor, Ki67, and prolyl 4-hydroxylase and significantly decreased CD45. The intervention comprising ADM decellularized from porcine skin by using SCCO2 and ASCs was proven to improve diabetic wound healing. The SCCO2 produced ADM-ASCs had a positive effect on epidermal regeneration, anti-inflammation, collagen production and processing, and cell proliferation; thus, it accelerated wound healing [35].
Cartilage tissue engineering that combines the triads of decellularized porcine cartilage graft as a scaffold, plasma rich platelet (PRP) as signal, and chondrocytes as the cell to attenuate anterior cruciate ligament transection (ACLT)-induced OA progression and regenerate the knee cartilage in rats. The SCCO2 decellularized porcine cartilage graft (dPCG) significantly reduced the ACLT-induced OA symptoms and attenuated the OA progression. The histological analysis depicted cartilage protection by dPCG. The repair and attenuation effect were proved by dPCG in the articular knee cartilage damage as evidenced by safranin-O, type II collagen, aggrecan, and SOX-9 immuno-staining. To conclude, intra-articular administration of dPCG with or without PRP is efficient in repairing the damaged cartilage in the experimental OA model [41]. A 3D composite was constructed using SCCO2-dPCG that promotes chondrogenic marker expression
A bioactive 3D histotypic SCCO2 decellularized nasal cartilage (dPNCG) construct was engineered with adipose-derived stem cells (ADSC) and chondrocytes and cultured for 21 days. The 3D histotypic constructs produced a solid mass of 3D histotypic cartilage with significant production of glycosaminoglycans. The SCCO2-dPNCG granules are bound to one another by extracellular matrix and proteoglycan, to form a 3D structure expressed chondrogenic markers such, as type II collagen, aggrecan, and SOX-9. The SCCO2-dPNCG substrate enabled the synthesis of type II collagen along with ECM to yield 3D histotypic cartilage. This engineered 3D construct might serve as a promising future candidate for cartilage tissue engineering in rhinoplasty [27].
Atelocollagen was prepared by using SCCO2 technology. To our knowledge, we are the first to use SCCO2 technology to produce atelocollagen. The sliced porcine skin was subjected to a proprietary SCCO2 for decellularization. The decellularized porcine skin scaffold was freeze-dried and freeze-milled to granules and subjected to enzymatic hydrolysis using pepsin in acidic conditions, then subjected to ultrafiltration for pepsin and telopeptide removal. The atelocollagen solution was filtered through a 0.2-μm filter for sterilization. The acidic atelocollagen solution was subjected to fibrillogenesis by bringing the pH to 7, then centrifuged to obtain the atelocollagen slurry. This slurry was then freeze-dried to obtain atelocollagen dry powder [34]. The whole process saves a lot of time and cost as compared to the traditional collagen purification process. Atelocollagen prepared by SCCO2 followed by pepsin digestion of the telo-peptides process showed complete removal of the telo-peptides as compared to the traditional purification process [34].
The SCCO2 technology was employed to decellularize porcine skin to produce a collagen matrix (Figure 6). This novel collagen matrix was developed to accelerate wound healing for hard-to-heal or delayed wound healing clinical conditions. The collagen matrix produced by SCCO2 technology from porcine skin is chemically comparable and biocompatible to human skin. The SCCO2 produced collagen matrix showed complete decellularization, the chemical content was found to be type I collagen and characteristic features were similar to that of humans. The collagen matrix proved to be non-toxic in
Porcine skin derived products.
The SCCO2 process was used for the decellularization of adipose tissue extracellular matrix [48]. The adipose tissue was subjected to the SCCO2 process for 3 h at 18 MPa and 37°C with the addition of ethanol as the cosolvent. The decellularized adipose tissue consisted of the extracellular matrix components and was free from lipids. The decellularized adipose tissue extracellular matrix can help the widespread coating progress the adhesion of cells due to the presence of active components such as collagen, laminin, elastin, fibronectin, and glycosaminoglycans. The coating of the decellularized adipose tissue extracellular matrix increases the proliferation of human endothelial cells isolated from umbilical vein, human adipose tissue-derived mesenchymal stem cells, human monocytic leukemia cells, and immortalized human keratinocytes on a plastic culture plate and does not induce the production of the proinflammatory phenotype of macrophages. The decellularized adipose tissue extracellular matrix was used as a model for the investigation of the action of anticancer drugs on cells for breast cancer, which is similar to the native condition [49]. The SCCO2 decellularization contrasts with the prevailing methods in the rapidity and cost-effective nature. Traditional methods of decellularization of adipose tissue include several freezing-thawing cycles, extraction of lipids with isopropanol, and enzymatic treatment [49, 50]. The development of the SCCO2 decellularization for the preparation of an extracellular matrix from adipose tissue is an environmentally friendly approach that will endorse the development of the methods of tissue engineering with the use of autologous material.
We produce tissue and organ scaffold using SCCO2 extraction technology, such as liver, kidney, heart, pancreas, artery, skin, bone, cartilage, and cornea [16]. Table 5 listed our works on the various tissue and organ scaffolds extracted by SCCO2 technology for tissue engineering applications [16]. The ultimate goal of TERM is to use the tissues and organs produced by SCCO2 from the porcine or bovine to regenerate the human tissues and organs (Figure 7). We hope to develop the whole animal application without any waste materials, which suits the purpose of the circular economy. Eventually, we intend to regenerate any human tissue and organ by its animal counterpart.
SCCO2 decellularized biomaterials for TERM.
Substantial progression in the field of TERM and scaffold biomaterials engineering by SCCO2 proposes extended potentials to acquire novel, effective achievements, which may be applied in biomedical applications. Recently, the interest in natural biomaterials produced by SCCO2 technology for medical devices production has increased, and a greater number of in-depth studies are done to better detect their likely applications related to chemical and physical characteristics and the extraction procedures, which do not modify their structural properties and biocompatibility. Tissue engineering approaches have become a valid alternative for body structure and function restoring, natural scaffold biomaterials produced by SCCO2 technology are also used as biomimetic scaffolds with controlled degradation rate
The SCCO2 decellularization technology as compared to other traditional processes is a minimally manipulated process and thus cost-effective, and gentle to the natural collagen scaffold ECM structure. Therefore, SCCO2 decellularized scaffolds might contain unaltered signals that are indispensable for stem cell adhesion, migration, homing, proliferation, and differentiation. No chemicals and solvents were involved in the process, therefore it is eco-friendly. It destroys bacteria and inactivates viruses during the process. SCCO2 technology costs only about 1/10th of the traditional process. Different tissues and organs from animals such as pigs, cows, horses, sheep can be used to produce decellularized scaffolds. The most important and key point is SCCO2 process drastically reduces immune rejection.
Our study indicated that the natural collagen scaffolds prepared by the SCCO2 process might be able to induce stem cell differentiation
This research was financially supported by the Southern Taiwan Science Park Bureau, (107SMIC-RC02; BX-01-03-05-108 and 108CB01), Taiwan, R.O.C.
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He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356823",title:"MSc.",name:"Seonghee",middleName:null,surname:"Min",slug:"seonghee-min",fullName:"Seonghee Min",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Daegu University",country:{name:"Korea, South"}}},{id:"353307",title:"Prof.",name:"Yoosoo",middleName:null,surname:"Oh",slug:"yoosoo-oh",fullName:"Yoosoo Oh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Yoosoo Oh received his Bachelor's degree in the Department of Electronics and Engineering from Kyungpook National University in 2002. He obtained his Master’s degree in the Department of Information and Communications from Gwangju Institute of Science and Technology (GIST) in 2003. In 2010, he received his Ph.D. degree in the School of Information and Mechatronics from GIST. In the meantime, he was an executed team leader at Culture Technology Institute, GIST, 2010-2012. In 2011, he worked at Lancaster University, the UK as a visiting scholar. In September 2012, he joined Daegu University, where he is currently an associate professor in the School of ICT Conver, Daegu University. Also, he served as the Board of Directors of KSIIS since 2019, and HCI Korea since 2016. From 2017~2019, he worked as a center director of the Mixed Reality Convergence Research Center at Daegu University. From 2015-2017, He worked as a director in the Enterprise Supporting Office of LINC Project Group, Daegu University. His research interests include Activity Fusion & Reasoning, Machine Learning, Context-aware Middleware, Human-Computer Interaction, etc.",institutionString:null,institution:{name:"Daegu Gyeongbuk Institute of Science and Technology",country:{name:"Korea, South"}}},{id:"262719",title:"Dr.",name:"Esma",middleName:null,surname:"Ergüner Özkoç",slug:"esma-erguner-ozkoc",fullName:"Esma Ergüner Özkoç",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Başkent University",country:{name:"Turkey"}}},{id:"346530",title:"Dr.",name:"Ibrahim",middleName:null,surname:"Kaya",slug:"ibrahim-kaya",fullName:"Ibrahim Kaya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"419199",title:"Dr.",name:"Qun",middleName:null,surname:"Yang",slug:"qun-yang",fullName:"Qun Yang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Auckland",country:{name:"New Zealand"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. 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