Tissue-Engineered Vascular Grafts

Cardiovascular diseases are still the leading cause of death in developed countries. Revascularization procedures such as coronary artery and peripheral bypass grafts, as well as access surgery represent a 2$ billion market yearly for the US alone. Despite intense research over many decades, no clinically suitable, shelf-ready, synthetic, vascular, small-caliber graft exists. There is therefore still a quest for such a clinical vascular prosthesis for surgical revascularization procedures and access surgery. Many approaches have been tried and are currently under investigation with promising results. These range from acellular and cell-based, stable or bio-degradable, synthetic scaffolds to biological or decellularized grafts, not forgetting self-assembly technologies for in vitro or in vivo VTE. All these approaches can be further enhanced by functionalization, e.g. with growth factors and drug elution. This updatable book aims tocover all the relevant aspects of Vascular Tissue Engineering (VTE) and novel alternatives to develop vascular grafts for clinical applications. The chapters in this book cover different aspects of manufacturing scaffolds with various polymers, mechanical characteristics, degradation rates, decellularization techniques, cell sheet assembly, 3-D printing and autologous mandril-based VTE. All the necessary in vitro tests such as biocompatibility and thrombogenicity are reviewed. Pre-clinical assessment of in vivo experimental models include patency, compliance, intimal hyperplasia, inflammatory reaction, cellular ingrowth and remodeling. Finally, early clinical trials will be periodically updated regarding results, regulatory aspects and post-marketing quality assessment. Furthermore, the reader should get an insight into various approaches, technologies and methods to better understand the complexity of blood surface and cell interactions in VTE. Translational research has yielded early human applications clearly showing the enormous need of research in the field to provide better solutions for our patients and this continuously updated book will hopefully become a reference in the field for life sciences.

Beat H. Walpoth, Beat H. Walpoth, M.D., P.D., FAHA, Emeritus, is a trained cardiovascular surgeon and past Director of Cardiovascular Research in the Department of Surgery at Geneva University Hospital, Switzerland. He obtained his medical degree in 1972 from the University of Zurich. Postgraduate training included 2 years at the Peter Bent Brigham, Harvard University, Boston (1973-75), and cardiac transplantation at Stanford University (1982-84). Teaching appointments held at Boston, Zurich, Bern, Geneva, and Verona Universities. Dr. Walpoth is a recipient of several national and international awards, including the ESAO Wichtig Award in 2008 and 2012 for his group's research on Tissue Engineered Vascular Grafts (TEVG). He has over 200 publications, of which more than 100 are firstauthor papers, in peer-reviewed journals. Dr. Walpoth is Past President of the European Society for Artificial Organs (ESAO) as well as the International Symposium on VTE (ISVTE) and has created theTERMIS Thematic Group on TEVG. His current main areas of interest include TEVG, cell therapy, transplantation, angiogenesis, blood flow measurements, as well as bio-artificial cardiovascular support. His future projects are to support the initiated changes from artificial to bio-artificial, i.e., tissue engineered organs, as well as continuing international teaching and networking in the field for better outcome of clinical applications.

Helga Bergmeister Helga Bergmeister obtained a degree in human medicine from the Medical University of Vienna (M.D.). Prior to that, she was educated in veterinary medicine at the University of Veterinary Medicine Vienna (Bachelor of Veterinary Medicine) and completed a postgraduate doctoral program (Doctor of Veterinary Medicine). Helga Bergmeister obtained education as an experimental surgeon in the Experimental Department of the II. Clinics of Surgery, Faculty of Medicine Vienna. Since 1991 she hasbeen employed at the Center for Biomedical Research, Medical University Vienna. Although Helga Bergmeister is involved in the whole spectrum of experimental studies at the University, the main focus of her work is dedicated to cardiovascular procedures and implants. Since many years she has been performing regulatory approvals as a principal investigator or study director. She is a member of the institutional animal ethics committee. Helga Bergmeister is a teacher in the Medical School and in the Doctoral program and in postgraduate Courses of the Medical University of Vienna. Her research interests are focused on the creation of small diameter vascular grafts made of natural and newly designed synthetic materials.
Gary Bowlin Dr. Bowlin n is a Professor and Herbert Herff Chair of Excellence at The University of Memphis in the Department of Biomedical Engineering. Dr. Bowlin received his Ph.D. from the University of Akron in Biomedical Engineering and subsequently completed an American Heart Association sponsored postdoctoral fellowship in the Department of Surgery at Akron City Hospital. In 1997, Dr. Bowlin started his first faculty appointment at Virginia Commonwealth University and rose to the rank of Professor and held the Louis and Ruth Harris Exceptional Scholar Professorship. In August 2013, he relocated to The University of Memphis to continue his research and entrepreneurial endeavors and training of the next generation of Biomedical Engineers. Dr. Bowlin's collaborative research has and continues to focus on the application of electrospun templates for tissue engineering and tissue regenerative applications, all in the pursuit of saving lives and improving the quality of life. Dr. Bowlin's laboratory has published extensively in these areas with over 140 peer-reviewed, highly-cited manuscripts. He is a Fellow of the National Academy of Inventors and the American Institute for Medical and BiologicalEngineering. He is also the Inaugural and current President of the International Society for Biomedical Polymers and Polymeric Biomaterials.
Deling Kong is a Deling Kong is a Professor of Biochemistry and Polymer Chemistry. He is currently the Chief, Office of Science and Technology of Nankai University. Dr. Kong received his Doctorate in Polymer Chemistry and Physics from Nankai University in 1997. He underwent his first postdoctoral training at the Center of Bioengineering, Rostock, Germany, from 1998 to 2000 and the second postdoctoral training in Brigham and Women's Hospital, Harvard Medical School, from 2000 to 2003. He came back to Nankai University in 2003. He was Director of the Key Laboratory of Bioactive Materials, Ministry of Education, from 2004 to 2017 and Dean of School of Life Science, Nankai University, from 2017 to 2018.His research interests mainly focus on vascular grafts, bioactive hydrogel, and stem cell for treatment of ischemic diseases. His group has contributed more than 30 patent applications and published over 300 peerreviewed papers. He is a recipient of several awards including the National Science and Technology Progress Award (2nd class), Tianjin Award of Natural Science (1st class), and Tianjin Award of Science and Technology Progress (2nd-class). He received the Outstanding Youth Fund in 2007. He was selected Fellow, Biomaterials science and engineering (FBSE) in 2016.

Joris Rotmans Joris Rotmans Joris Rotmans is an internist-nephrologist and Associate Professor in the Department of Nephrology of Leiden University Medical Center (LUMC) in the Netherlands. He obtained his master's degree in Medicine (cum laude) from the Free University in Amsterdam. He received his Ph.D. in 2005 from the University of Amsterdam on new therapeutic strategies for vascular access for hemodialysis whereupon he started his residency in Internal Medicine. In 2008-2009, he did postdoctoral research on vascular tissue engineering at the Australian Institute of Bioengineering and Nanotechnology in Brisbane, Australia. Since 2010, he combines clinical work as internist-nephrologist with vascular and renal research in the Department of Nephrology at LUMC. His main focus of research is vascular access for hemodialysis. He was the principle investigator of the DialysisXS consortium in which a novel method to generate in vivo engineered blood vessels was developed. He is co-founder of VACIS BV, a spin-off company that aims to bring in situ engineered blood vessels to the clinic. In 2014, he received a prestigious VIDI grant from NWO that allowed him to expand his research group and to continue his research on vascular access for hemodialysis. He is the principle investigator of the LIPMAT trial, a multicenter, randomized clinical trial in the Netherlands in which the efficacy of liposomal prednisolone to enhance AVF maturation is evaluated. Dr. Rotmans is Board Memberof the Vascular Access Society and Chair of the Thematic Working Group on Vascular Tissue Engineering of TERMIS.

Peter Zilla's Peter Zilla is an academic Cardiovascular and Thoracic Surgeon who is Chief of Adult and Paediatric Cardiothoracic Surgery at Cape Town's Groote Schuur and Red Cross Children's Hospitals, Director of the Cardiovascular Research Unit, Co-Director of the Cape Heart Institute, and CEO of Strait Access Technologies at the University of Cape Town, South Africa. He holds an M.D. degree from the University of Vienna, a Dr.Med. degree from the University of Zurich, a Ph.D. from the University of Cape Town, and a P.D. (habil) from the University of Vienna. In his capacity as Chief of the Christiaan Barnard Department, where the first human heart transplantation was performed in 1967, he has built up a training program for cardiothoracic surgeons from the African continent.

His main research foci have consistently been in the fields of tissue engineering and prosthetic cardiovascular implants. Pioneering tissue engineering since 1983, he initiated an international multicenter study with in-vitro endothelialisation of peripheral bypass grafts culminating in more than 400 patient-implants. His second focus, improving heart valve prostheses for the young patients of developing countries, has led to tissue treatments that extend the longevity of heart valve prostheses manifold.

His engagement in the field of rheumatic heart disease has additionally awarded him international recognition as a leader in this field when he united all major cardiothoracic surgical societies worldwide under one umbrella (Cardiac Surgery Intersociety Alliance/CSIA), thereby creating a worldwide platform for the establishment of local cardiac surgical capacity in regions of the world that are endemic for RHD but have no access to open heart surgery. Addressing this challenge also from another side, he co-founded a University of CapeTown Start-Up Company in 2008 under the name "Strait Access Technologies" (SAT), securing a leading global position in innovative concepts for trans-catheter heart valve technologies for the patients and resources of lowto middle-income countries.

He is author of almost 200 peer-reviewed full papers and inventor of 41 filed or issued US/PCT patents, having been cited almost 10,000 times with an h-index of 51. He is the editor of 6 books and has authored numerous book chapters. He obtained significant international academic and industry grants and was the recipient of several international awards.