PIs: Michael S. Sacks, Ph.D.
Co-PIs: Dr. Joyce Bischoff, Dr. David Brown, Dr. Danielle Gottlieb, Dr. John Mayer, Dr. Robert Padera, Dr. Andrew Powell, Dr. Virna Sales, Dr. Frederick Schoen, Dr. George Stetten
Title: Mechanisms of In-Vivo Remodeling in Tissue Engineered Heart Valves
Description: Using autologous cells and biodegradable polymers, tissue engineered pulmonary valves (TEPV) have been fabricated and have functioned in the pulmonary circulation of growing lambs for up to 20 weeks, with tissue evolving into a differentiated layered structure resembling that of native valve. More recent studies have demonstrated that use of bone marrow mesenchymal stem cells (BMSC) and PGH/PLLA scaffolds produce functioning implants for up to 8 months in growing lambs which also demonstrated in-vivo structural evolution. These studies have demonstrated the feasibility of engineering pulmonary valve (PV) leaflets and segments of main pulmonary artery (PA) in-vitro. Both stuctures have functioned well without thrombosis. Moreover, both the gross and microscopic characteristics of the TEPV structures began to approximate those of normal tissues, strongly suggesting that cell phenotypes evolved in a directed fashion to remodel the valvular and vascular tissue. The goal of the current research program is to quantify and simulate tissue remodeling events that occur post-implantation, and to understand the factors that influence the remodeling rate and the quality and architecture of the ultimate tissue. Specifically, we hypothesize that TEPV implant remodeling is primarily mediated by the level of in-vivo mechanical stimuli to the interstitial cells and developing ECM. Mechanical stimuli will affect the rate of scaffold degradation and the degree of post-implant cellular ingrowth.
Source: NIH-National Heart, Lung and Blood Institute
Term: 4 years
Amount: $3.3 million