Xenograft Heart Valves--Biomechanics/Collagen Structure
1 R43 HL53088-1,
Though allograft human aortic valves are preferred for transplantation by virtue of their lowthrombogenicity and immunogenicity, superior hemodynamic performance, and extended durability, onlyabout 2,000 per year are implanted due to limited donated heart supply. An acellular porcine heart valvecould form the substrate of a heart valve graft after the removal of native cells and soluble proteins toablate its immunogenicity under conditions that do not alter the structural proteins of the leaflets. Thisextracellular matrix substrate can be then be repopulated with autogenous (recipient) fibroblasts whichwould synthesize proteins critical for the long-term maintenance of leaflet function as well as maskresidual xenoantigens. These studies will concentrate on the effects of the depopulation process on thebiomechanical functions of porcine heart valve leaflets with corollary examinations of the collagencontent and collagen cross-linking in treated tissues. Various depopulation paradigms will be comparedwith the goal of minimizing changes in stress/strain relationships, stress/relaxation relationships, ultimatetensile strength, and bending stiffness as compared with fresh cellular valve leaflets. While most of theexaminations will utilize tissue from adult pigs, it is clear that the type and stability of collagencross-links may change with age. Since certain target populations for heterograft valves may requireimplantation of smaller diameter valves, additional studies will focus on heart valve leaflets from juvenilepigs weighing 12-25 kg in which the diameter of the aortic valve is approximately 13-16 mm as opposedto 22-29 mm in adult animals. Since biomechanical properties and hemodynamic performance areclosely related, these examinations should help optimize the performance of depopulated heart valvesas graft elements.
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Principal Investigator:Steven Goldstein
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