Beth Israel Deaconess Medical Center
		The vascular surgery research laboratory has been extensively involved in two main areas of vascular biology research: 1) evaluating the mechanisms responsible for prosthetic graft failure and 2) developing novel biomaterial surfaces in order to modulate the body’s response to the biomaterial. Anastomotic intimal hyperplasia (AIH) remains as the most common cause of delayed prosthetic arterial graft failure, a consequence of focal, unregulated gene expression. As graft healing occurs, genes are either up- or downregulated compared to a quiescent arterial wall. Our hypothesis is that this altered gene expression results in cellular proliferation, migration and extracellular matrix production by smooth muscle cells, leading to AIH. The significance and unique aspect of this work is that our group is the first to identify specific genes that are altered following prosthetic arterial grafting in vivo and examine their role in the cellular environment in vitro. This research, which is in its 20th year, is funded by a R01 grant from the National Heart Lung and Blood Institute at the National Institutes of Health. The other aspect of our research is to develop novel cardiovascular device surfaces for both peripheral and cardiac applications. Several novel surfaces have been developed and are currently being evaluated both in vitro and in vivo. We have designed and patented a novel, biocompatible Dacron vascular graft that has the following properties: 1) reduced porosity via sealing with a novel ionic urethane, 2) mechanical properties comparable or superior to the pre-coated Dacron substrate and 3) localized immobilization of select proteins to the graft surface. This composite graft has been characterized in vitro and will be assessed in vivo this year. Another project currently ongoing is to developing a novel small-diameter (4mm internal diameter) prosthetic vascular graft using nanofiber technology with surface antithrombin properties. We are also evaluating a novel infection-resistant Dacron prosthetic valve sewing cuff with optimum antimicrobial properties in vivo by applying the quinolone antibiotic ciprofloxacin using thermofixation (pad/heat) dyeing.				Another project currently ongoing is developing a novel titanium surface via covalent linkage of recombinant hirudin to silane that is bound to chemisorbed oxygen on the titanium surface. Titanium is used extensively in prosthetic heart valves, dental implants, artificial organs and mesh. Lastly, we have been evaluating in vivo an infection-resistant polyurethane via application of quinolone antibiotics using textile dyeing techniques. These materials would be utilized in a wide range of implantable devices such as catheters, wound dressings and vascular grafts. All of the biomaterial research is funded by small-business grants from the National Institutes of Health. The vascular surgery research laboratory is the lead laboratory for a T32 research training program from the National Institutes of Health. This program is designed to provide two years of intense basic research training in vascular surgery for future academic clinicians. The training program addresses the absence of adequate research training for vascular surgeons as it applies to specific areas of clinical disease. Trainees pursue a program of research activity supplemented with course work in research design, ethics, statistics and evaluation of published research in the areas of molecular and cell biology, biomechanics, coagulation and thrombosis and angiogenesis. Clinically relevant problems such as atherogenesis, intimal hyperplasia, prosthetic/host interactions and thrombosis are the main focus of these research projects. Trainees carry out their research projects under the guidance of a faculty advisor selected from 20 renowned vascular researchers based at four Harvard Medical School hospitals (Beth Israel Deaconess Medical Center, Brigham and Women’s, Children’s Hospital (Boston) and Joslin Diabetes Institute) and the Massachusetts Institute of Technology. Upon completion of the program, trainees are capable of independent research and possess the scientific and research background necessary to obtain peer-reviewed funding.
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