SBIR-STTR Award

The development of an alternative to the currently available synthetic vascular prosthesis is of great value. Atherosclerosis vascular disease, in the form of coronary artery and peripheral vascular disease, is the leading cause of mortality in the United States. Despite vast improvements in the field of biomaterials, a useful biocompatible material is still not available for the production of small vascular grafts largely because of blood clotting/thrombosis. To overcome this problem, Dr. David B Masters, GeI-Del Technologies, Inc., has developed a patented fabrication process that uses purified proteins, water and other biochemicals to produce biomimetic material in the shape of tubes that can mimic the wall structure of blood vessels (Gel-Del TM Vasograft). Pure collagen and elastin is mixed together to create a non-woven material without protein denaturation. This material has the capacity to act as a therapeutic delivery system to allow biochemical and pharmacological intervention of graft failure and host remodeling (e.g., heparin to prevent thrombosis; growth factors for capillary formation). Vasograft can be made into conduits of any dimension, including small to medium vascular reconstructions: coronary, femoral, renal, carotid. In vitro results show that Vasograft TM has all the necessary functional and structural characteristics to become clinically useful, that is: mechanical strength >500mmHg, weeks of non-thrombogenicity from heparin release, compliance, suture strength/ reapproximation, semipermeability, fast endothelial cell attachment/migration, >50 percent elasticity, and porosity. The principal investigator's hypothesis is that implantation of Vasograft TM in arterial circulation will result in a functional and durable vascular bioprosthesis. The biologic nature of this graft will facilitate native cellular in-growth and potential "neovessel" formation. Success in these studies will lead to development of Vasograft TM for humans. Aim: 1. To prepare and evaluate Vasograft TM for vascular reconstruction, using 2.5 mm (i.d.) and 1-2cm long Vasografts TM as small diameter arterial graft in animal studies. 2a. To evaluate the patency rates of Vasograft TM as a small diameter arterial reconstruction conduit in a pig model for 30 days. 2b. To evaluate the histological characteristics of Vasograft TM after implantation in pigs.

Thesaurus Terms:
biomaterial development /preparation, biomimetics, blood vessel, blood vessel prosthesis, implant, protein engineering, tissue engineering blood vessel restoration, collagen, elastin medical implant science, swine

Atherosclerotic vascular disease, in the form of coronary artery and peripheral vascular disease, is the leading cause of mortality in the United States. Despite vast improvements in the field of biomaterials, a useful biocompatible material is still not available for the production of small vascular grafts largely because of blood clotting/thrombosis. To overcome this problem, Dr. David B. Masters, Gel-Del Technologies, Inc., has developed a patented fabrication process that uses purified proteins, water, and other biochemicals to produce biomimetic material in the shape of tubes that can mimic the wall structure of blood vessels (Gel-Del VasoGraft(tm)). Type I collagen and elastin proteins, along with the anti-clotting factor, heparin, are processed together and coated onto a cotton mesh scaffolding to create a tubular conduit (VasoGraft(tm)). Completed SBIR Phase I studies demonstrate excellent bio- and hemocompatibility, anti-clotting, and host tissue integration and in vivo patency out to at least 32 days in a porcine femoral artery model. While the lumen within the graft itself remained open, significant intimal hyperplasia occurred at the anastomosis sites, suggesting that the surgical injury created an adverse repair response. Because the graft itself functioned well, it is hypothesized that reduction of the anastomotic intimal hyperplasia will allow greater long term function and patency. The studies proposed within this Phase II application will utilize the proven Bravo(tm) Drug Delivery Polymer system from Surmodics, Inc., currently utilized in the Cypher(tm) drug (Sirolimus)- eluting stent (produced by Cordis, Inc.), to release Sirolimus, an inhibitor of smooth muscle cell proliferation, from the ends of the VasoGraft, creating VasoGraft-S(tm). In vitro studies will analyze the release kinetics and bioactivity of Sirolimus released from these VasoGraft-S(tm) constructs, and long-term porcine studies will test its function in vivo out to 300 days, with the ultimate goal of developing the VasoGraft-S(tm) for human trials. These studies will be executed as follows: Aim 1: Measure the release kinetics of different doses of Sirolimus(tm) from VasoGraft(tm) in vitro to determine optimal drug incorporation strategy; Aim 2: Assess optimal dose of Sirolimus(tm) for reducing stenosis in 30 and 60 day porcine femoral artery grafts; and Aim 3: Evaluate the patency rates of Gel-Del Vasograft(tm) with Sirolimus(tm) release in long term (i.e., 120 and 300 day) porcine femoral artery grafts.

Thesaurus Terms:
antithrombogenic surface, biomaterial compatibility, biomaterial evaluation, biomimetics, blood vessel prosthesis, collagen, drug delivery system, elastin, heparin, sirolimus, tissue engineering artery, biomaterial development /preparation, cardiovascular pharmacology, cell proliferation, dosage, hyperplasia, restenosis, vascular smooth muscle bioengineering /biomedical engineering, biotechnology, medical implant science, swine