Though allograft human aortic valves are preferred for transplantation by virtue of their low thrombogenicity and immunogenicity, superior hemodynamic performance, and extended durability, only about 2,000 per year are implanted due to limited donated heart supply. We propose that an acellular porcine heart valve could form the substrate of a heart valve graft after the removal of native cells and soluble proteins to ablate its immunogenicity under conditions that do not alter the structural proteins of the leaflets. This extracellular matrix substrate can be then be repopulated with autogenous (recipient) fibroblasts which would synthesize proteins critical for the long-term maintenance of leaflet function as well as mask residual xenoantigens. The proposed studies will concentrate on the effects of the depopulation process on the biomechanical functions of porcine heart valve leaflets with corollary examinations of the collagen content and collagen cross-linking in treated tissues. Various depopulation paradigms will be compared with the goal of minimizing changes in stress/strain relationships, stress/relaxation relationships, ultimate tensile strength, and bending stiffness as compared with fresh cellular valve leaflets. While most of the examinations will utilize tissue from adult pigs, it is clear that the type and stability of collagen cross-links may change with age. Since certain target populations for heterograft valves may require implantation of smaller diameter valves, additional studies will focus on heart valve leaflets from juvenile pigs weighing 12-25 kg in which the diameter of the aortic valve is approximately 13-16 mm as opposed to 22-29 mm in adult animals. Since biomechanical properties and hemodynamic performance are closely related, these examinations should help optimize the performance of depopulated heart valves as graft elements.
