Tissue heart valves: Current challenges and future research perspectives

Substitute heart valves composed of human or animal tissues have been used since the early 1960s, when aortic valves obtained fresh from human cadaver s were transplanted to other individuals as allografts. Today, tissue valve s are used in 40% or more of valve replacements worldwide, predominantly as stented porcine aortic valves (PAV) and bovine pericardial valves (BPV) pr eserved by glutaraldehyde (GLUT) (collectively termed bioprostheses). The p rincipal disadvantage of tissue valves is progressive calcific and noncalci fic deterioration, limiting durability. Native heart Valves (typified by th e aortic valve) are cellular and layered, with regional specializations of the extracellular matrix (ECM). These elements facilitate marked repetitive changes in shape and dimension throughout the cardiac cycle, effective str ess transfer to the adjacent aortic wall, and ongoing repair of injury incu rred during normal function. Although GLUT bioprostheses mimic natural aort ic valve structure (a) their cells are nonviable and thereby incapable of n ormal turnover or remodeling ECM proteins; (b) their cuspal microstructure is locked into a configuration which is at best characteristic of one phase of the cardiac cycle (usually diastole); and (c) their mechanical properti es are markedly different from those of natural aortic valve cusps. Consequ ently, tissue valves suffer a high rate of progressive and age-dependent st ructural valve deterioration resulting in stenosis or regurgitation (>50% o f PAV overall fail within 10-15 years; the failure rate is nearly 100% in 5 years in those <35 years old but only 10% in 10 years in those >65). Two d istinct processes-intrinsic calcification and noncalcific degradation of th e ECM-account for structural valve deterioration. Calcification is a direct consequence of the inability of the nonviable cells of the GLUT-preserved tissue to maintain normally low intracellular calcium. Consequently, nuclea tion of calcium-phosphate crystals occurs at the phospholipid-rich membrane s and their remnants. Collagen and elastin also calcify. Tissue valve miner alization has complex host, implant, and mechanical determinants. Noncalcif ic degradation in the absence of physiological repair mechanisms of the val vular structural matrix is increasingly being appreciated as a critical yet independent mechanism of valve deterioration. These degradation mechanisms are largely rationalized on the basis of the changes to natural valves whe n they are fabricated into a tissue valve (mentioned above), and the subseq uent interactions with the physiologic environment that are induced followi ng implantation. The "Holy Grail" is a nonobstructive, nonthrombogenic tiss ue valve which will last the lifetime of the patient (and potentially grow in maturing recipients). There is considerable activity in basic research, industrial development, and clinical investigation to improve tissue valves . Particularly exciting in concept, yet early in practice is tissue enginee ring, a technique in which an anatomically appropriate construct containing cells seeded on a resorbable scaffold is fabricated in vitro, then implant ed. Remodeling in vivo, stimulated and guided by appropriate biological sig nals incorporated into the construct, is intended to recapitulate normal fu nctional architecture. (C) 1999 John Wiley & Sons, Inc.