R01HL157017

Preclinical Assessment of a Compliance Matched Biopolymer Vascular Graft - Project Summary

There are approximately 250,000 coronary artery bypass graft (CABG) procedures performed annually to treat coronary heart disease (CHD), with graft failure rates reported to be as high as 42.8%. A major cause of graft failure in CABG has been attributed to graft compliance mismatch, leading to subsequent intimal hyperplasia and graft thrombosis. The development of a compliance matched functional small diameter vascular graft will therefore significantly improve the treatment of those with CHD.

Tissue engineering has shown promise in achieving some but not all of the required characteristics for a functional tissue engineered vascular graft (TEVG). A particularly challenging aspect in the development of a functional TEVG is the design of a fully biodegradable biopolymer graft that can be tuned to a desired compliance pre-implantation and subsequently maintain its compliance as it degrades and remodels in-vivo. As such, there is a critical need to develop a compliance matched TEVG that remains compliance matched throughout the host remodeling process while also maintaining a functional endothelium.

To meet this need, we will develop and functionally assess a tropoelastin layered and endothelialized TEVG that is and remains compliance matched. We will utilize computational simulation to optimize the compliance of a biodegradable gelatin/tropoelastin layered TEVG that elutes TGFB2 in a controlled manner to promote early cell infiltration and late matrix deposition in our graft, thus stabilizing its compliance as our graft degrades. The overall working hypothesis of our research is that the intravital (in-vitro and in-vivo) compliance of our graft can be maintained by temporally controlling TGFB2 elution from a computationally optimized TEVG.

We will test this hypothesis by completing the following specific aims. Aim 1 of our research project will assess if compliance and TGFB2 elution can maintain the compliance of our TEVG in-vivo using a rat aortic interpositional implantation model. Aim 2 of our proposed work will assess the function of our TEVG in a preclinical large animal (sheep carotid) implantation model.

The proposed studies will establish a novel pre- and post-implantation compliance controlled fully biodegradable biopolymer TEVG with excellent patency, anti-thrombogenicity, vasoreactivity, and functional performance.

University Of Pittsburgh - Of The Commonwealth System Of Higher Education

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Pennsylvania United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 377% from $658,593 to $3,139,611.