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, MD, PD, FAHA, is a trained cardiovascular surgeon, past Director of Cardiovascular Research in the Department of Surgery at Geneva University Hospital, Switzerland. He obtained his medical degree in 1972 at Zurich University, followed by Board of Surgery (including thoracic and cardiovascular) in 1982. Postgraduate training included two years at the Peter Bent Brigham, a Harvard university hospital, Boston (1973-75) and cardiac transplantation at Stanford University (1982-84). Teaching appointments were held at Harvard Medical School, Universities of Bern and Geneva (Emeritus) and still ongoing in Verona University (Visiting Professor). Dr. Walpoth is a recipient of several national and international awards, including the European Society for Artificial Organs (ESAO) Wichtig Award in the years 2008 and 2012 for his group’s research on Vascular Tissue Engineering. He has over 150 publications, of which more than 50 are first-author papers, in peer reviewed journals. Past-president of the ESAO; organizer of the Annual Congresses of the ESAO in 2000 in Lausanne, and 2008 in Geneva. He has also been responsible for the bi-annual Swiss Experimental Surgery Symposium (2006, 2008, 2010, 2012 and 2016). As from 2004 he is a member of the International Faculty for Artificial Organs and the Director of the Internationally Co-tutored PhD Course in Biotechnology and Bioengineering (Universities of Geneva and Verona) since 2005. Currently, he holds the presidency of the International Symposium on Vascular Tissue Engineering (ISVTE) and has created the TERMIS Thematic Group on Vascular Tissue Engineering. His current main areas of interest include vascular tissue engineering and bio-artificial cardiovascular support.

Helga Bergmeister has a background in veterinary and humane medicine. She is committed to the management of the Center for Biomedical Research of the Medical University of Vienna. She is involved in the implementation of preclinical research projects and regulatory testing. Beside she heads a small research group whose work is dedicated to the development of small diameter vascular grafts using new designed biomaterials and different fabrication techniques.
Gary Bowlin 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 post-doctoral fellowship in the Department of Surgery at Akron City Hospital. Dr. Bowlin’s collaborative research has and continues to focus on the application of electrospun templates for tissue engineering and tissue regenerative applications as well as developing hemostatic products, 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 130 peer-reviewed manuscripts. Google Scholar data shows his group’s published works have been cited over 14,000 times, resulting in an H-index of 50. To date, Dr. Bowlin has been granted 13 U.S. Patents and over 30 foreign patents. These patents have helped to start five different companies and several commercially available and regulatory agency cleared products. One of the most recent technologies being developed by St. Teresa Medical, Inc. has completed clinical trials for CE Marking. The latest company, Sweetbio, Inc., is Memphis based and commercializing (FDA 510K application submitted December 2017) novel guided tissue regeneration membranes for dental reconstruction procedures. As a result of this inventiveness and impact, he was recently inducted as a Fellow into the National Academy of Inventors. He is also the Inaugural and current President of the International Society for Biomedical Polymers and Polymeric Biomaterials.

Joris Rotmans is an internist-nephrologist and associate professor at the Department of Nephrology of the Leiden University Medical Center (LUMC) in the Netherlands. He obtained his master’s degree in Medicine (cum laude) at the Free University in Amsterdam. He received his PhD in 2005 at 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 at the Department of Nephrology of the 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 allows 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. Furthermore, he is co-PI of the K+onsortium, a Dutch consortium funded by the Dutch Kidney Foundation ( 1.250.000, -), focused on potential protective effects of potassium supplementation in CKD patients.

Peter Zilla’s academic qualifications are an MD (University of Vienna), DrMed. (University of Zurich); ＂Habilitation＂ (PD;University of Vienna) and PhD (University of Cape Town). He is a registered general-, vascular- and cardiothoracic surgeon. After 3 years in basic science (University Zurich 1981-1983); he did his surgical residency at the the University Hospital Vienna (1983-1989), senior-residency at the University Hospital Zurich (1989-1990); held staff-surgeon positions in Austria and Cape Town and has been Head of the Chris Barnard Department of Cardiothoracic Surgery for the past two decades. He published >200 full papers; >40 US/PCT patents and has an H-factor of 45.