In this Phase I SBIR project, ?Synthetic Resorbable AV Graft?, we propose a new paradigm in vascular grafts and patient treatment with the development of a novel, fully synthetic, AV graft with off-the-shelf availability. This unique interdisciplinary project combines the tissue engineering and surgical experience of Dr. Narutoshi Hibino in the Cardiac Surgery Department at Johns Hopkins University Hospital (Baltimore, MD) and the clinically proven expertise of synthetic nanofiber scaffolds from Dr. Jed Johnson at Nanofiber Solutions (Hilliard, OH). Through this innovative product development collaboration, we hypothesize that our fully resorbable, synthetic nanofiber, vascular graft will result in dramatically improved patient care by eliminating risk of immune rejection, graft infection, and providing a graft that remodels into a fully functional neovessel with no foreign material remaining in the body. According to the American Society of Nephrology, more than 300,000 Americans have end stage renal disease (ESRD) and are dependent on artificial dialysis to stay alive. Arteriovenous (AV) fistulae are commonly constructed to create vascular access for hemodialysis. However, access failure is currently one of the leading causes of hospitalization for patients with ESRD. Infection and early thrombosis of non-resorbable synthetic grafts such as those made from expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate (Dacron) prevent these procedures from having better success rates. A solution for vascular access and other vascular diseases may be provided by biodegradable, nanofiber tissue engineered vascular grafts (TEVGs). A carotid artery to jugular vein AV graft implantation in a sheep model (N=4 at a 3 month time point) will be used in this study since we already have extensive mouse, rat, and low-pressure (i.e venous circulation) sheep data. With this project, we will accomplish our proposed specific aims: 1) Investigate key mechanical properties of our AV scaffold throughout complete degradation using an in vitro degradation chamber per ASTM 1635, and 2) Evaluate the safety and efficacy of our AV scaffold in a sheep model for 3 months.
In this work, we will develop fully synthetic, bioresorbable, arteriovenous grafts utilizing electrospun nanofibers for vascular access in patients undergoing hemodialysis. These tissue engineered vascular grafts will address limitations with currently available commercial products such as high infection risk and high rate of thrombosis.
