Classification of skin substitutes by various properties.
\\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:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"7126",leadTitle:null,fullTitle:"Prostatectomy",title:"Prostatectomy",subtitle:null,reviewType:"peer-reviewed",abstract:"The prostate gland is one of the male organs that have changed over the years. Those changes lead to a disruption of the quality of life and risk of prostate cancer in men over 50 years of age. In the era of prostate-specific antigen it is possible to overcome prostate cancer through early diagnosis. This made it possible to treat the diagnosis of prostate cancer and prevent the development of prostate cancer disease in the patient. In addition, early diagnosis has led to advances in the technological development of the basic surgical technique - prostatectomy. This book contains the efforts of a number of doctors and scientists interested in the prostate gland from different countries around the world. Some of these studies are likely to pose new challenges and trends in the diagnosis of the prostate gland and basic surgical technique.",isbn:"978-1-83880-685-9",printIsbn:"978-1-83880-684-2",pdfIsbn:"978-1-83880-686-6",doi:"10.5772/intechopen.73923",price:119,priceEur:129,priceUsd:155,slug:"prostatectomy",numberOfPages:184,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"ffd82b0f0d267e6d98b8c68afebbd7b2",bookSignature:"Tsvetin Genadiev",publishedDate:"May 29th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/7126.jpg",numberOfDownloads:10143,numberOfWosCitations:3,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:15,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:27,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 14th 2018",dateEndSecondStepPublish:"March 7th 2018",dateEndThirdStepPublish:"May 6th 2018",dateEndFourthStepPublish:"July 25th 2018",dateEndFifthStepPublish:"September 23rd 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"29780",title:"Associate Prof.",name:"Tsvetin",middleName:"Trifonov",surname:"Genadiev",slug:"tsvetin-genadiev",fullName:"Tsvetin Genadiev",profilePictureURL:"https://mts.intechopen.com/storage/users/29780/images/6739_n.jpg",biography:"Dr. Tsvetin Genadiev attended the High Medical Education at High Medical University, Faculty of Medicine, Sofia, Bulgaria from 1987 till 1994. From 1994 till 1998 he had a Residency training in Urology at High Military Medical Academy, Sofia, Bulgaria.\nHis interests are Prostate, Prostate Cancer and BPH, Diagnosis, Laparoscopic Urology, Radical prostatectomy, HDR Brachytherapy in prostate cancer and Thulium Laser prostate surgery.\nIn 2007 he obtained a PhD Degree in Laparoscopic Lymph Node Dissection in Prostate Cancer and in 2010 he became Associate Professor of Urology at University of Sofia, Bulgaria.\nHe has published many papers on Laparoscopy, Laparoscopic Extraperitoneal Approach for Urinary Bladder, and Stones Removal. He has also published a monograph on Laparoscopic Urology and is Editorial boards member of few Medical Journals. Dr. Genadiev is currently consultant urologist in Vita Hospital, Sofia, Bulgaria.",institutionString:null,position:"Consultant urologist",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1079",title:"Genitourinary Oncology",slug:"genitourinary-oncology"}],chapters:[{id:"64354",title:"Introductory Chapter: Prostatectomy - Challenge in the Past and Today",doi:"10.5772/intechopen.81804",slug:"introductory-chapter-prostatectomy-challenge-in-the-past-and-today",totalDownloads:862,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Tsvetin Trifonov Genadiev",downloadPdfUrl:"/chapter/pdf-download/64354",previewPdfUrl:"/chapter/pdf-preview/64354",authors:[{id:"29780",title:"Associate Prof.",name:"Tsvetin",surname:"Genadiev",slug:"tsvetin-genadiev",fullName:"Tsvetin Genadiev"}],corrections:null},{id:"62783",title:"Biomarkers for Diagnosis and Prognosis of Prostate Cancer",doi:"10.5772/intechopen.79726",slug:"biomarkers-for-diagnosis-and-prognosis-of-prostate-cancer",totalDownloads:2200,totalCrossrefCites:6,totalDimensionsCites:10,hasAltmetrics:1,abstract:"Since its discovery, elevated prostate-specific antigen (PSA) has been the measurement to indicate possibility of prostate cancer, as well as biochemical recurrence following treatment. Although PSA has led to decrease in prostate cancer–related mortalities, PSA is a nonspecific prostate cancer biomarker reflective of other prostate-related conditions such as benign prostatic hyperplasia (BPH), resulting in a high false-positive rate. This has led to overtreatment of men with clinically insignificant disease. While most prostate cancer patients have slowly progressive disease and should be treated conservatively, roughly 10% of patients will progress to have metastatic disease, of which the majority of prostate cancer deaths can be attributed. Stratifying these patients based on prognosis so that they may benefit from aggressive treatment is critical to their survival. Biomarkers for prostate cancer diagnosis and subsequent prognostic screening have significantly advanced this field. Here, we review some of the current blood, tissue, and urine biomarker tools used to measure an array of molecules including DNA, RNA, protein, or even epigenetic modifications. Utilizing the technologies described here, as well as looking to the future, correct early identification of prostate cancer with powerful prognostic value is much closer than ever before.",signatures:"Meghan A. Rice and Tanya Stoyanova",downloadPdfUrl:"/chapter/pdf-download/62783",previewPdfUrl:"/chapter/pdf-preview/62783",authors:[null],corrections:null},{id:"62261",title:"Pre-Therapeutic Dosimetry Employing Scandium-44 for Radiolabeling PSMA-617",doi:"10.5772/intechopen.79157",slug:"pre-therapeutic-dosimetry-employing-scandium-44-for-radiolabeling-psma-617",totalDownloads:1058,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"In recent years, the positron emitter scandium-44 moved into the focus of research providing favorable nuclide properties for an application in nuclear medicine. Radiolabeling of PSMA-617 with scandium-44 as diagnostic match for [177Lu]Lu-PSMA-617 instead of gallium-68 would enable pre-therapeutic dosimetry in clinical setting. Due to the chemical similarities of scandium and lutetium, the in vitro and in vivo characteristics of [177Lu]Lu-PSMA-617 are more similar to [44Sc]Sc-PSMA-617 than to the 68Ga-compounds [68Ga]Ga-PSMA-617 or [68Ga]Ga-PSMA-11. [44Sc]Sc-PSMA-617 showed its potential in a clinical setting as a PET imaging agent of prostate cancer providing several advantages over gallium-68 labeled tracers. The longer half-life of the nuclide would allow, for example, an optimized patient management and treatment, long-term or late time point imaging as well as transportation to more distant PET centers. However, especially clinical applications like individual dosimetry or intraoperative applications are still under investigation.",signatures:"Elisabeth Eppard",downloadPdfUrl:"/chapter/pdf-download/62261",previewPdfUrl:"/chapter/pdf-preview/62261",authors:[{id:"245845",title:"Dr.",name:"Elisabeth",surname:"Eppard",slug:"elisabeth-eppard",fullName:"Elisabeth Eppard"}],corrections:null},{id:"62775",title:"Bipolar Endoscopic Enucleation of Big Benign Prostate Enlargement",doi:"10.5772/intechopen.79125",slug:"bipolar-endoscopic-enucleation-of-big-benign-prostate-enlargement",totalDownloads:948,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Large benign prostatic enlargement (BPE) has been a major health problem and the surgical management could be technically challenging to urologists due to the limitation of conventional monopolar transurethral resection of prostate. Bipolar endoscopic enucleation of prostate aimed to remove the adenoma of BPE by stepwise adenoma devascularization and maximal adenoma removal through minimally invasive surgery. In this chapter we described the general principle, the surgical techniques of bipolar endoscopic enucleation and the related modifications of the technique in the recent years. As compared with open prostatectomy, bipolar endoscopic enucleation avoided the wound complications but achieved similar functional outcome. Bipolar endoscopic enucleation also allowed much more adenoma removal comparing with transurethral resection of the prostate. Unlike Holmium laser or thulium laser enucleation of the prostate, the required instruments for bipolar endoscopic enucleation of the prostate were familiar and more readily available to most urologists.",signatures:"Wai Hee Steve Chan, Chi Fai Kan and Churk Fai Trevor Li",downloadPdfUrl:"/chapter/pdf-download/62775",previewPdfUrl:"/chapter/pdf-preview/62775",authors:[null],corrections:null},{id:"62468",title:"Laparoscopic Simple Prostatectomy",doi:"10.5772/intechopen.79549",slug:"laparoscopic-simple-prostatectomy",totalDownloads:1027,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Benign prostatic hyperplasia (BPH) is the most common benign tumor and cause of urinary retention in middle-aged male patients. Transurethral resection of the prostate (TURP) is the gold standard surgical treatment for benign prostatic obstruction. Although widely performed, TURP is associated with significant morbidity. Open prostatectomy is performed in larger glands, which are more than 80 grams, with higher morbidity. Advances in technology, such as holmium laser enucleation of the prostate (HoLEP) and KTP laser vaporization, are other options that are widely used despite their limitations. Laparoscopic simple prostatectomy (LSP) is a minimally invasive treatment option with equivalent functional outcomes and is useful in larger prostatic adenomas, with low morbidity in experienced hands.",signatures:"Yusuf Ilker Comez",downloadPdfUrl:"/chapter/pdf-download/62468",previewPdfUrl:"/chapter/pdf-preview/62468",authors:[null],corrections:null},{id:"64606",title:"Endoscopic Extraperitoneal Transvesicocapsular Adenomectomy of Prostate (EETAP): A New Operative Method with an Innovative Learning Protocol for Its Performance",doi:"10.5772/intechopen.82225",slug:"endoscopic-extraperitoneal-transvesicocapsular-adenomectomy-of-prostate-eetap-a-new-operative-method",totalDownloads:996,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The standard surgical treatment of obstructive symptoms of the lower urinary tract by benign prostatic hyperplasia is transurethral resection or classical simple prostatectomy. Inspired by our experience with laparoscopic radical prostatectomy and for the protection of urethra from stricture during prolonged transurethral resection, we studied the literature and started a prospective study for performing a laparoscopic simple prostatectomy. Following informed patient consent, we performed laparoscopic extraperitoneal simple prostatectomy in 17 patients with moderate to severe obstructive symptoms of benign prostatic hyperplasia with a prostate volume of over 80 ml. We did not find a laparoscopic technique for a simple prostatectomy which is the same as our method that we describe and publish. We called our method endoscopic extraperitoneal transvesicocapsular adenomectomy of prostate. We identified an abbreviation for the method of its popularization and systematic presentation, EETAP. In this chapter, we publish for the first time in the literature a minimally invasive surgical method for endoscopic extraperitoneal transvesicocapsular prostate adenоmectomy. We describe and publish the details of the method, the abbreviation of the method, an innovative learning protocol for its performance, as well as hypotheses for preoperative and intraoperative differential diagnosis. In our opinion, a multicenter study of this method could lead to its standardization in the broad urological practice.",signatures:"Genadiev Tsvetin Trifonov",downloadPdfUrl:"/chapter/pdf-download/64606",previewPdfUrl:"/chapter/pdf-preview/64606",authors:[{id:"29780",title:"Associate Prof.",name:"Tsvetin",surname:"Genadiev",slug:"tsvetin-genadiev",fullName:"Tsvetin Genadiev"}],corrections:null},{id:"62329",title:"Reduced Port Extraperitoneal Laparoscopic Radical Prostatectomy",doi:"10.5772/intechopen.79364",slug:"reduced-port-extraperitoneal-laparoscopic-radical-prostatectomy",totalDownloads:987,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Robot-assisted laparoscopic prostatectomy (RALP) is more popular than laparoscopic radical prostatectomy (LRP) in twenty-first century. However, RALP is still an expensive surgery. Open radical prostatectomy (ORP) was a gold standard and not an expensive surgery. However, ORP is not minimum invasive. LRP is relative expensive and minimum invasive. The problem of RALP or LRP is necessary to spread the wound for removing prostate and the pain of wound is often a problem. Using U-shaped incision at umbilicus, spreading the wound is not necessary to remove prostate. Single-port surgery is a challenging procedure for surgeons in spite of faster recovery and higher patient satisfaction than conventional laparoscopy. Adding one or two port, reduced port surgery is easier than single-port surgery. Reduced port LRP is an extension of conventional LRP. The procedure is as same as conventional LRP. Curved or flexible instruments are not always necessary in the reduced port LRP. Reduced port LRP has less pain and better cosmetics than conventional LRP because the prostate is removed from the umbilicus. It is not necessary to spread the wound for removing prostate.",signatures:"Kazuhiro Araki and Yukio Naya",downloadPdfUrl:"/chapter/pdf-download/62329",previewPdfUrl:"/chapter/pdf-preview/62329",authors:[null],corrections:null},{id:"62729",title:"Preventing Erectile Dysfunction after Radical Prostatectomy: Nerve-Sparing Techniques, Penile Rehabilitation, and Novel Regenerative Therapies",doi:"10.5772/intechopen.79398",slug:"preventing-erectile-dysfunction-after-radical-prostatectomy-nerve-sparing-techniques-penile-rehabili",totalDownloads:2071,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Erectile dysfunction is a known and much-dreaded functional consequence of radical prostatectomy. Dr. Patrick Walsh pioneered the nerve-sparing radical retropubic prostatectomy in the early 1980s, which has mitigated the morbidity of this surgery. Post-operative potency rates range widely from 20 to 80%, however, and depend on myriad factors including age, preoperative potency, and degree of nerve-sparing during surgery. Over the past four decades several developments have continued to offer hope to patients and clinicians alike, including refined understanding of cavernosal nerve neuroanatomy, beneficial modifications in surgical technique, as well as the advent of robotic surgery. Furthermore, multiple pre- and post-operative penile rehabilitation techniques using mechanotherapy and pharmaceuticals have also improved functional recovery. This paper examines erectile dysfunction as a consequence of radical prostatectomy, including the physiology of erections, the pathophysiology of post-operative erectile dysfunction, novel surgical techniques to enhance neurovascular bundle preservation, and penile rehabilitation strategies involving hyperbaric oxygen, neuroprotective pharmaceuticals, dehydrated human amnion-chorion membrane allografts, and mesenchymal stem cell therapy.",signatures:"Michael Whalen",downloadPdfUrl:"/chapter/pdf-download/62729",previewPdfUrl:"/chapter/pdf-preview/62729",authors:[null],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3274",title:"Advances in Prostate Cancer",subtitle:null,isOpenForSubmission:!1,hash:"fb7257d982e3228ceb9320f595ae1c58",slug:"advances-in-prostate-cancer",bookSignature:"Gerhard Hamilton",coverURL:"https://cdn.intechopen.com/books/images_new/3274.jpg",editedByType:"Edited by",editors:[{id:"67794",title:"Prof.",name:"Gerhard",surname:"Hamilton",slug:"gerhard-hamilton",fullName:"Gerhard Hamilton"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1312",title:"Advances in Cancer Management",subtitle:null,isOpenForSubmission:!1,hash:"dc1cad15f23e313cd067e7e7b4511005",slug:"advances-in-cancer-management",bookSignature:"Ravinder Mohan",coverURL:"https://cdn.intechopen.com/books/images_new/1312.jpg",editedByType:"Edited by",editors:[{id:"58197",title:"Prof.",name:"Ravinder",surname:"Mohan",slug:"ravinder-mohan",fullName:"Ravinder Mohan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"789",title:"Emerging Research and Treatments in Renal Cell Carcinoma",subtitle:null,isOpenForSubmission:!1,hash:"616688465519d2b5bcb1d867a3806714",slug:"emerging-research-and-treatments-in-renal-cell-carcinoma",bookSignature:"Robert J. Amato",coverURL:"https://cdn.intechopen.com/books/images_new/789.jpg",editedByType:"Edited by",editors:[{id:"73752",title:"Dr.",name:"Robert",surname:"Amato",slug:"robert-amato",fullName:"Robert Amato"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"559",title:"Bladder Cancer",subtitle:"From Basic Science to Robotic Surgery",isOpenForSubmission:!1,hash:"117cbfaa858282ed2cdb9a81ce411def",slug:"bladder-cancer-from-basic-science-to-robotic-surgery",bookSignature:"Abdullah Erdem Canda",coverURL:"https://cdn.intechopen.com/books/images_new/559.jpg",editedByType:"Edited by",editors:[{id:"69657",title:"Prof.",name:"Abdullah Erdem",surname:"Canda",slug:"abdullah-erdem-canda",fullName:"Abdullah Erdem Canda"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5256",title:"Human Papillomavirus",subtitle:"Research in a Global Perspective",isOpenForSubmission:!1,hash:"8d66d3c0bc41a12be8217ca0cee52b60",slug:"human-papillomavirus-research-in-a-global-perspective",bookSignature:"Rajamanickam Rajkumar",coverURL:"https://cdn.intechopen.com/books/images_new/5256.jpg",editedByType:"Edited by",editors:[{id:"120109",title:"Dr.",name:"Rajamanickam",surname:"Rajkumar",slug:"rajamanickam-rajkumar",fullName:"Rajamanickam Rajkumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1845",title:"Prostate Cancer",subtitle:"Diagnostic and Therapeutic Advances",isOpenForSubmission:!1,hash:"3be3f6b756cec080cfcacd2251b62a5c",slug:"prostate-cancer-diagnostic-and-therapeutic-advances",bookSignature:"Philippe E. Spiess",coverURL:"https://cdn.intechopen.com/books/images_new/1845.jpg",editedByType:"Edited by",editors:[{id:"64476",title:"Dr.",name:"Philippe E.",surname:"Spiess",slug:"philippe-e.-spiess",fullName:"Philippe E. 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\r\n\tNowadays, all types of businesses ranging from the smallest e-com stores to the biggest corporations, use data to run operations. There are billions of bytes of data getting generated every minute. However, raw data doesn’t come in that handy on its own. There are many data management tools and applications. SQL or Structured Query Language is one of the programming languages which is used to communicate with the databases for the creation, deletion, and retrieval of data from it. The ability to use SQL will help you get more out of your data than just reading it. It can be used for ad-hoc data analysis and reporting and more extensive projects involving multiple tables and complex applications.
\r\n\r\n\t
\r\n\tSQL is worth learning because it’s a programming language that’s in demand in the tech industry and in other sectors that need technology. Most software developers who know SQL earn respectable salaries. Learning SQL can not only enhance your skills, but it can also give you a better understanding of the applications you work with daily. In this book, we will go through the details of SQL and how to use it effectively. The goal of this book is to have many practical application examples that will help learners easily acquire and self-study SQL.
The skin is the largest organ of the body and is responsible for many essential functions that no skin substitute has been able to fully replicate to date. Skin substitutes can be defined as any material used to provide biologic wound coverage on a temporary or permanent basis. Skin substitutes may be differentiated from simple, inert, wound dressings in that they possess properties that allow them to enhance repair of skin after injury, expedite regeneration and improve scar quality [1, 2, 3].
Epidermal and superficial partial thickness burns have the potential to heal by epidermal regeneration from adnexal nests of epidermal stem cells with minimal scarring, provided the burn wound remains protected and free from infection. Conventional management of debrided deep dermal and full thickness burns has been to achieve wound closure with autologous skin grafts since they were first introduced in the nineteenth century. Early wound closure minimises the severity of scarring and functional impairment caused by permanent dermal loss. However, autologous skin graft donor site availability is frequently limited in major burn patients, particularly when the total body surface area of burn (TBSA) exceeds 25%. Donor site morbidity from skin autograft harvest includes acute physiological insult to the burn patient, blood loss, pain and additional wounding and scarring. Allograft and xenografts are less desirable than autograft due to inherent issues with delayed graft rejection and risk of infection.
A vast array of skin substitutes have been developed through advances in tissue engineering and biomaterials. Skin substitutes have not yet eliminated the requirement for autologous skin grafting in deep or full thickness burns. However, they have the potential to circumvent some issues associated with autologous graft in terms of availability or lack thereof, donor site morbidity and failure to adequately replace dermal elements in deeper injuries. Skin substitutes can provide clinical benefits in terms of wound healing that have been outlined, as follows [4]:
Protect the wound from infection and loss of fluid
Provide a stable and biodegradable template for the synthesis of neodermal tissue
Either host or enable the influx of cells that will function as dermal cells, producing dermal tissue rather than scar tissue
Allow ease of handling and resist tear forces
Simplified classification systems can aid clinicians in selection of appropriate skin substitutes for burn wound reconstruction. Robust classifications can also benefit research efforts by allowing comparison of outcomes across a growing range of available skin substitutes, categorised based on their properties.
Skin substitutes encompass a diverse group of materials and may be classified based on five main properties [5, 6, 7], as outlined with examples in Table 1.
Permanence: Temporary or permanent
Material source: Biological (either natural biological or constructed biological dermal substitutes), synthetic or mixed (biosynthetic) dermal substitutes
Layering: Single layer, bilayer, multilayer
Replaced region: Epidermal component only, dermal component only, composite (dermal and epidermal components)
Cellularity: Acellular or cellular
Skin substitute properties | Subgroups | Examples of materials used in burn wounds |
---|---|---|
Permanence | Temporary | Allograft, Amniotic membrane, Biobrane, Suprathel, Alloderm, Apligraf |
Permanent | Biodegradable Temporising Matrix (BTM), Integra, Matriderm | |
Material source | Biological | Allograft, Amniotic membrane, Alloderm, Apligraf, Matriderm |
Biosynthetic | Integra, Biobrane, Dermagraft | |
Synthetic | Biodegradable Temporising Matrix (BTM), Suprathel | |
Layering | Single layer | Alloderm, Matriderm, Suprathel, Cultured Epithelial autograft |
Bilayer | Biobrane, Integra, BTM | |
Replaced region | Epidermal | Epicel, Recell, Suprathel, Cultured Epithelial autograft, Biobrane |
Dermal only | Alloderm, Dermagraft, Matriderm | |
Composite | Allograft, Apligraf, Integra, BTM | |
Cellularity | Acellular | Integra, BTM, Matriderm, Biobrane, Suprathel |
Cellular | Allograft, Amniotic membrane, Epicel, Recell, Apligraf, Dermagraft |
Classification of skin substitutes by various properties.
This classification system inspired by factorial design reported by Davison-Kotler et al. (Figure 1) [7]. borrows elements from four earlier classification systems which have been summarised in Table 2 [8, 9, 10, 11]. Classification systems can be helpful to both researchers in comparing outcomes of different skin substitutes and to clinicians who need to understand their composition in order to make an appropriate selection based on the clinical scenario faced.
Skin substitute classification adapted from Davison-Kotler et al. [
Classification system author | Description | Categories |
---|---|---|
Balasubramani [8] | Categorised by the tissue layer the produce replaces | Class I: Substitutes consisting of cultured epidermal equivalent only (e.g., Epicel) Class II: Substitutes consisting of dermal components from processed skin or manufactured with extracellular matrix proteins such as collagen (e.g., Dermagraft) Class III: Composite skin substitutes including both dermal and epidermal components (e.g., Integra) |
Kumar [9] | Categorised by the tissue layer the product replaces, layering and material source | Class I: Temporary, impervious, materials that replace epidermal function (e.g., Suprathel) Class II: Epidermal (e.g., Epicel or dermal skin substitutes (e.g., Matriderm or Alloderm) Class III: Composite skin substitutes replacing both layers (e.g., Integra, BTM) |
Ferreira [10] | Categorised by location, permanence, and material source with lettering system | Permanence: Origin: Location: |
Vyas and Vasconez [11] | Categorised by cellularity, the tissue layer the product replaces and permanence | This review suggested categorisation of skin substitutes based on cellularity in addition to the tissue layer the product is replacing and the permanence of the skin substitute |
Davison-Kotler [7] | Incorporated elements from all four above classifications | Algorithmic system fully outlined in Figure 1. Five properties used to categorise skin substitutes: Permanence: Temporary (biodegradable)/Permanent (nonbiodegradable) Material Source: Natural (i.e., Biological)/Synthetic/Both Layering: Single layer/Bilayer Replaced region: Epidermis/Dermis/Both Cellularity: Acellular/Cellular |
Chronological development of skin substitute classification systems.
Classifications have evolved over time in parallel with advancements in skin substitute design. A commonality to all classification systems was an emphasis placed on the tissue layer replaced by the skin substitute in question, be it epidermal, dermal or composite skin replacement. This concept marries well with standard categorisation of burns and other wounds by the depth of injury when planning reconstructive requirements. Earlier classification systems failed to differentiate between products based on permanence [8], material source [8] and cellularity [8, 9, 10]. The omission of these integral features created classification systems that were non-intuitive and confusing, whereby some dissimilar products could be placed in the same category or qualify for multiple categories.
The system outlined by Davison-Kotler et al. [7] allows multiple key properties to be simultaneously incorporated, since all skin substitutes possess a variety of characteristics. This multifactorial classification system allows for clear and comprehensive descriptive categorisation of commercially available skin substitutes with potential to expand to include novel skin substitutes still under development. A glossary to further expand on the examples skin substitutes provided in this chapter is found in Table 3. This list is not exhaustive and many additional commercially products are available but it serves to illustrate the classification systems outlined, with a particular focus on materials utilised commonly in contemporary management of burns and other extensive wounds.
Skin substitute (manufacturer) | Structure | Mechanism of action and limitations |
---|---|---|
Allograft (N/A) | Human cadaveric split-thickness skin grafts. Available cryopreserved or glycerol preserved. | Vascularises temporarily as per autograft but is a passive temporizer with eventual rejection after 3–4 weeks. Fresh allograft confers risk of disease transmission due to retention of residual DNA. |
Amniotic membrane (N/A) | Innermost layer of placenta consisting of epithelial layer, basement layer and avascular stroma, hyaluronan and decorin. Available cryopreserved or glycerol-preserved. | Promotes epithelial cell migration and adhesion with anti-inflammatory and anti-scarring properties. Efficacious in protecting the wound bed and reducing bacterial load but has poor mechanical stability. |
Alloderm (Lifecel corporation) | Acellular cadaveric human dermis, processed to remove epidermis and cells | Provides a scaffold for fibroblast and vascular ingrowth, single stage reconstruction with autologous graft. Limitations include antigenicity, availability and shelf life. |
Apligraf (Organogenesis Inc.) | Cultured human foreskin-derived neonatal fibroblasts in a bovine type I collagen matrix with stratified keratinocytes | Provides a scaffold for host cell migration and population with barrier function provided by keratinocyte layer. Inconsistent cell survival, collagen composition and vascularisation. |
Biobrane (Smith & Nephew) | Silicone membrane bonded to porous nylon mesh impregnated with cross linked T1 porcine collagen peptides | Dermal collagen peptides allow adherence to the wound, semipermeable outer membrane allows exudate drainage and evaporative water loss control, e.g., partial thickness burns/donor sites. |
Biodegradable Temporising Matrix (BTM) (Novosorb Polynovo®) | Completely synthetic dermal scaffold composed of impermeable polyurethane seal overlying layer of biodegradable polyurethane foam | Bi-layered dermal matrix widely used in acute and delayed burn wound reconstruction. Robust integration and neo-vascularisation reported even in application to infected or avascular wounds such as exposed tendon. |
Cultured Epidermal Autograft (N/A) | Keratinocytes cultured from biopsy of autologous skin. 3-week turnaround for 10,000-fold keratinocyte expansion. Culture process which may use murine fibroblasts and foetal calf serum. | Variable graft take and poor long term graft stability in large and deep burn wounds due to poor regeneration of basement membrane proteins which have key role in epidermal adhesion and skin homeostasis. Processing times long and costly. Culture using animal derived cells carries risk of immunogenicity and prion disease transmission. |
Dermagraft (Intercytex Ltd.) | Cryopreserved cultured neonatal dermal fibroblasts on a bioresorbable polyglactin mesh | Provides scaffold of extracellular matrix consisting of growth factors and collagens, tenascin, vitronectin, and GAGs. |
Epicel (Vericel Corporation) | Petroleum gauze and autologous keratinocyte sheets co-cultured with murine cells | 2–8 mm cell layers thick, indicated for deep dermal and full-thickness burns |
Integra (Integra LifeSciences) | Biosynthetic dermal scaffold composed of polysiloxane polymer overlying cross-linked T1 bovine collagen and shark glycosaminoglycan (chondroitin-6-sulphate) | Bi-layered dermal matrix widely used in two-stage acute and delayed burn wound reconstruction. Available in single layer of collagen only for single stage reconstruction. Infection during integration phase generally requires removal or replacement. |
Matriderm (Medskin Solutions) | Single layer of non-crosslinked bovine collagen and tendon derived elastin hydrolysate. 1 or 2 mm thick matrices available. | Dermal matrix which provides neodermis for autograft application either as one stage (1 mm construct) or two staged (2 mm construct) procedure. |
ReCell (Avita Medical) | Autologous keratinocytes obtained from cultured autologous skin biopsy, suspended in solution that can be sprayed onto wound bed | Accelerated epithelialisation from in vivo wound models but human application and long term wound stability remains controversial and further independent clinical studies ongoing. Fibroblasts and melanocytes also delivered to wound |
Suprathel (Polymedics Innovations) | Microporous, absorbable synthetic copolymers, mostly polylactic acid | Similar indications for use as Biobrane with no biologic component. |
Glossary with description of skin substitutes in alphabetical order.
Skin substitutes can be subdivided into two groups with distinct objectives and indications in burn care with regards to their permanence: namely temporary and permanent skin substitutes. Permanence may be defined by biodegradability as described in the classification reported by Davison-Kotler et al. [7] However, many bilayered skin substitutes such as Integra and Biodegradable Temporising Matrix, (BTM), have a non-biodegradable outer component that requires removal before autografting of a slowly biodegradable scaffold following ingrowth of host cellular material (no polyurethane residues present by 18 months in the case of BTM) [12]. A more intuitive definition preferred by the authors of this chapter has been provided by Ferreira et al. [10] who describes the distinction as follows: Temporary skin substitutes ‘refer to those that remain in the wound for the period of time necessary to modulate and improve the characteristics of the lesion and are replaced by autogenous grafts. Permanent materials are those that restore part or the total structure of the skin and remain on the wound bed even after a possible grafting of autogenous skin for complete coverage of the lesion.’ Similarly, permanence is defined by the FDA as any material persisting more than 30 days in a wound, therefore permanence does not imply infinite presence in a wound.
Temporary skin substitutes do not generally achieve full integration with the wound bed. However, they may temporarily adhere while they promote healing by protecting, reducing water loss and accelerating epithelialisation.
The
Examples: Cadaveric allograft, Amniotic membrane, Biobrane, Suprathel
Permanent skin substitutes are generally composed of constructs or scaffolds that become integrated with the wound architecture by hosting or allow ingrowth of dermal cells, before eventual scaffold reabsorption.
The
Examples: Biodegradable Temporising Matrix (BTM), Integra
As the name suggests, biologic skin substitutes are made using biological materials from human or animal sources. Synthetic material refer to non-biological materials engineered in a laboratory to replace or support regeneration of one or more components of normal skin structure. Biosynthetic skin substitutes are those made using a combination of biological and synthetic materials. Skin substitutes with biological components may allow replication of a more natural neodermal structure generated by native extracellular matrix and can allow excellent re-epithelialisation, although staged procedures are often necessary due to slow vascularisation. Synthetic skin substitutes offer increased control over scaffold composition and less propensity to loss due to cross-species antigenicity or infective complications [16] as compared with materials with biological origins, following integration with the burn wounds to which they applied.
Single layered skin substitutes replace either the epidermal (e.g., Suprathel) or dermal (e.g., Matriderm) component of skin, the latter of which requires autologous skin grafting to complete the epidermal reconstruction. Bilayered dermal substitutes are designed to replace or replicate both dermal and epidermal layers during their application whether this is on a temporary basis (e.g., Biobrane) or a permanent basis (e.g., Integra, BTM). In the latter case a two-stage approach is required whereby the impermeable pseudo-epidermal layer is removed or ‘delaminated’ prior to autologous skin graft application for definitive wound closure. A two staged strategy is particularly advantageous in major burn patients by allowing autologous skin harvest to be deferred until such time as the patient has reached a point of physiological stabilisation, resolution of inhalational injury or other concomitant traumatic injury [12] and optimisation of cardiac or other medical comorbidities [17]. This approach also facilitates re-epithelialisation of donor site harvest for repeated harvest in major burn patients who may have a paucity of donor site due to their total body surface area of burn, while permitting mobilisation during the integration phase [18].
Skin substitutes can be categorised based on their ability to replace the epidermal, dermal or composite (epidermal and dermal) layers of skin. Epidermal replacement should, in theory, be sufficient for reconstruction of burn wounds and other wound with intact dermal elements. However, deeper dermal and full thickness injuries ultimately require epidermal and dermal reconstruction in order to achieve robust wound healing while minimising scar formation and loss of function. Replication of basement membrane and dermal-epidermal junction are one of several scientific challenges that has yet to be overcome by advanced skin substitute design (discussed in further detail in Section 2.5), in order to attain stable skin coverage for deep tissue injuries [19, 20].
Cellular skin substitutes contain viable cells such as keratinocytes or fibroblasts and as such they may incite an immunogenic host response due to antigenicity. These materials are bioengineered from human sources such as Dermagraft (source material: neonatal foreskin). The inclusion of cellularity as a property of skin substitutes was necessary given its implications for wound indications, risk of rejection, cost and regulatory issues.
To appreciate the use of skin substitutes in acute burn care an understanding of the pathophysiology of burn injury is essential. A burn is a defined an injury to tissues induced by heat, cold, friction, chemical, radiation or electrical energy. With regards to the utilisation of dermal substitutes for cutaneous burn wounds, the three most important factors are depth, size and anatomical location of the cutaneous burn.
Burn depth can be epidermal only, dermal (ranging from superficial to deep dermal) or full thickness. In real terms there are only two burn depths. In the first group the burns are superficial enough to heal spontaneously with acceptable functional and aesthetic outcome. These burns are classified as epidermal, superficial partial thickness and mid-dermal. The treatment is supportive and the corner stay is prevention of infection, which can deepen the burn and the control of pain. Pain control facilitates dressing changes and improves compliance with therapy and mobilisation. These burns heal spontaneously as there is an adequate volume of undamaged residual dermal tissue in the burn bed, as well as nests of epidermal cells located in the invaginated sheaths of adnexal structures. This results in re-epithelisation.
The second group (deep dermal to full thickness burns) undergo prolonged healing with granulation tissue and wound contracture, resulting in secondary intention healing. The treatment priorities for this group of burns is to abort the process of secondary intention healing replace it as closely as possible with primary intention healing. The surgical methods for doing this include excision and direct closure of small burns and burn wound excision with split thickness skin grafting for larger burns.
As burn size increases the treatment options become more complex. Small burns of any depth can generally be managed with dressings or relatively minor procedures. For the more superficial burns increasing burns size results in increasing the frequency and volume of dressings, restricting mobility and more likely to cause pain. For deeper burns that require skin grafting the larger the burn the smaller the area of “donor” site for skin graft harvesting. The skin grafts are subsequently “meshed” to allow a greater surface area to be covered. The larger the size of the burn the smaller the donor site area becomes resulting in thinner grafts with wider mesh patterns and subsequent poorer scarring outcomes. Additionally, for burns of over 50% TBSA there may not be enough skin donor site to close the debrided burn wounds. Skin grafts can be harvested from the same donor site, but the area must be healed first, and temporising options are required to cover the debrided wounds.
Burns over joints can be challenging to manage. Superficial burns require early mobilisation to prevent stiffness and deeper burns require meticulous debridement and skin grafting and intensive mobilisation. Debrided full thickness burns may result in the exposure of deeper structures such as tendon and bone. This results in unfavourable reconstruction if skin graft is used alone and often skin graft failure.
For superficial partial thickness burns where the epidermis and a variable amount of dermis is damaged skin substitutes designed to replace the epidermal layer are of value, particularly in larger burns and burns of the hands and joints. Examples of materials that are commonly used as epidermal substitutes in acute burns include:
Biobrane
Suprathel
To be of benefit epidermal substitutes must be applied shortly after the burn injury, preferably within 24–48 hours. The burn wound must be meticulously cleaned and residual debris including particulate matter and detached epidermis removed. Shaving the skin is also recommended as is a through wash with iodine solution. Application under general anaesthetic or sedation is recommended as the preparation may be painful. Mobilisation can begin at 48 hours and once the substitute has adhered. Dressing changes will only require the outer layers to be removed at the substitute should remain intact and undisturbed. Within 2–3 weeks it is expected that the substitute will detach as the skin beneath re-epithelialises. It is imperative to monitor for infection and if this occurs the substitute must be removed and conventional dressings applied. The risk of infection can be reduced with meticulous burn wound preparation and consideration of antibiotics.
Epidermal substitutes play an important role in the management of burns that are destined to heal themselves by preventing infection (which may convert the burn into a deep dermal/full thickness injury that will not heal by itself) and treating pain (allowing patients to tolerate dressing changes, early mobilisation and expediting hospital discharge).
The early definitive closure of burn wounds is problematic when the total body surface area exceeds 50% as burn are begins to exceed the available skin donor site area. Dermal substitutes in this setting are used to actively temporise the wound bed until split skin grafting can be performed. Examples of dermal substitutes commonly used in acute burns include:
Integra
Biodegradable Temporising Matrix (BTM)
The dermal matrix strategy was developed to combat these issues. Pioneered by Burke and Yannis [1, 2], the strategy involved producing a scaffold to allow autologous tissue in growth and establish a neo-dermis. The material developed, Integra, is a cross-linked type 1 collagen scaffold supported by shark chondroitin-6-suplahte glycosaminoglycan. It is physiologically closed with a bonded pseudo-epidermis of silicone. The expense of the product and issues arising from placing non-vascularised biological material on the surface of a wound in an immune compromised patient and anticipating neovascularisation without infection has resulted in variable usability and success in acute burns. The cost of this product often limits its use to very large burn wounds or as a ‘patch-up’ to cover persistent wounds that remain following primary auto-grafting procedures.
The development of biodegradable polymers and, at the start of this millennium, a completely synthetic, biodegradable polyurethane dermal matrix was designed and developed in Adelaide, Australia, using biodegradable polymer developed in Melbourne, Australia; this is known as the NovoSorb Biodegradable Temporising Matrix (BTM; Polynovo). The synthetic composition means that is not prone to infection by micro-organisms and if it does occur it is localised, not requiring removal or replacement [16]. The loss of skin graft over integrated BTM is uncommon and as also observed with Integra, the appearance of the meshed graft is considerably improved compared to autografting alone. The presence of a ‘neo-dermis’ provides a bed across which interstitial epithelialisation can occur without needing granulation tissue and so the cosmetic appearance is improved. In fact, the thinner the graft, the better the appearance and the less obvious the mesh pattern. The presence of a ‘neo-dermis’ provides a bed across which interstitial epithelialisation can occur without needing granulation tissue and so the cosmetic appearance is improved. In fact, the thinner the graft, the better the appearance and the less obvious the mesh pattern
The long-term outcome of scarring for survivors of large burn injuries is unpredictable. Skin grafted areas can form unstable pathological scars resulting in itch, pain and reduced function, particularly if the burn scar cross joints. Additionally, the aesthetic appearance is less than ideal.
A method to treat this involves scar excision and re-surfacing using dermal substitutes and split skin grafting. The introduction of skin substitute is beneficial in two ways. Firstly, the secondary contracture associated with using split skin grafts is reduced when using a dermal interface. Secondly the scar quality and pliability is improved when split skin grafting is used in conjunction with skin grafting. Frequently used skin substitutes in secondary burn wound reconstruction include:
Matriderm
Integra
Biodegradable temporizing matrix
The surgical technique for scar excision remains constant but the choice of dermal substitute is dependent upon surgeon preference, size of defect and patient choice.
The application of Matriderm involves a single stage procedure, which may be preferable to the staged reconstruction required for both Integra and BTM. The wound bed requires meticulous preparation and application of Matriderm. It can be challenging to use over large defects and is sheet split skin grafting rather than meshed is generally required and therefore requires available and good quality donor sites [5, 8].
Integra requires a two-stage application, firstly the excision of the scar application of the dermal substitute. Then, once integrated, delamination and application of split skin grafting. Timing between the two procedures varies dependent upon integration. As burn resurfacing is an elective surgery the risk of infection with Integra is somewhat mitigated in comparison to its use in acute burn wound care. The functional and aesthetic outcome of Integra has been observed to be reliable [1, 2, 3, 5, 8].
Similar to Integra BTM is a two-stage procedure. The patient can be managed in an outpatient setting until integration is completed. The risk of infection in an elective setting is minimal due to the synthetic nature of the product and the aesthetic and functional outcomes are comparable with the more established dermal substitutes [12, 16, 17, 18].
The ideal skin substitute does not yet exist. The following features have been proposed as desirable properties to consider in the development of novel skin substitutes [5, 6].
Inexpensive and cost-effective
Easy to store with long shelf life
Non-antigenic or low antigenicity
Durable and resistant to shear but flexible
Prevents evaporative water loss
Tolerant of hypoxia
Presence of dermal and epidermal components
Provides a bacterial barrier and resist infection
Rheology comparable to skin—drapes and conforms well
Easy to prepare, secure and store
Grows with patient growth (suitable for paediatric wounds)
Avoids scar hypertrophy/contracture
Single stage application
Several scientific and regulatory challenges must be overcome in the development of the aspirational ideal skin substitute. Creating an anatomical and physiological substitute for normal skin is a challenge faced by burns and trauma patients that has involved tissue bioengineers, polymer chemists, cellular and molecular biologists, surgeons, nurses, and therapists. A critical challenge in skin substitute design has been replication or regeneration of basement membrane the undulating dermal-epidermal junction which it produces through a process of paracrine dialogue between fibroblasts and keratinocytes. This specialised junction is responsible for limiting shear by establishing a molecular bond that anchors the cellular epidermis to the extracellular matrix of the dermis [19, 20].
As such, epidermal-only substitutes may offer a clinical adjunct to expedite reepithelialisation in conjunction with other wound reconstruction strategies but are insufficient in replication of autologous skin graft due to their limited expansion rate, mechanical fragility on handling, tendency to blister in vivo and vulnerability to shear after application. Reconstructive strategies using novel composite epidermal-dermal constructs [21, 22, 23], although challenging to engineer, offer theoretically increased wound stability compared with combining separate dermal and epidermal substitutes which lack the critical component of a functional dermal-epidermal junction required for long term graft stability. A randomised comparison of an engineered skin substitute with autograft [22] (autologous keratinocytes and fibroblasts attached to a collagen-based scaffold) in 15 paediatric patients demonstrated reduced mortality and requirements for donor skin harvesting, for autografting of full- thickness burns of greater than 50% TBSA. A pre-clinical study of a fibrin-based human skin substitute [23] with epidermal and dermal components (fibroblasts cultured in fibrin gel with keratinocytes seeded on top) carried out on in vitro deep burn necrotic tissue showed similar outcomes compare with split-thickness skin graft, concluding that this could potentially represent a viable management option for deep burn injuries, without the need for autologous skin graft. The challenge of further clinical research efforts will be to evaluate and compare between the ever-growing variety of reconstructive strategies that have been made possible due to the wide array of skin substitute products now commercially available.
New frontiers of research are being forged through clinical translation of advanced tissue bio-engineering techniques combined with 3D printing technology [24, 25, 26] to produce novel bi-layered and even tri-layered constructs with hypodermis [25]. Positive clinical results obtained with autologous and allogeneic TESSs based on human adult skin cells and human mesenchymal stem cells regarding successful engraftment (60–90% in the majority of studies [24]) safety, re-epithelialization and wound healing rates, are promising. Takami et al. has developed a TESS composed of autologous cultured keratinocytes, fibroblasts, and cadaveric de-cellularised allogenic dermal matrix.
This skin substitute demonstrated at 96% graft survival rate in four patients with debrided full thickness burn wounds with no delayed graft loss [27]. Although many tissue engineered skin substitutes (TESS) remain at pre-clinical development stage, they offer hope that the ultimate goal of developing an ideal skin substitute is attainable through further clinical research efforts.
This chapter outlines classification systems for skin substitutes and their evolution over time in line with advances in skin engineering technology, evidence supporting their clinical applications with regards to acute and secondary burn wound reconstruction and future advances toward the aspirational goal of developing an ideal dermal substitute.
Professor John Greenwood designed and developed the skin substitute known as Novosorb Biodegradable Temporising Matrix (BTM) and has a small residual shareholding with the company that manufactures this product, Polynovo.
Dr. Elizabeth Concannon and Dr. Lindsay Damkat-Thomas have no conflicts of interest to declare.
Intro
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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. 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