Current Progress in Anticalcif ication for Bioprosthetic and Polymeric Heart Valves.
The use of bioprosthetic valves fabricated from fixed heterograft tissue (porcine aortic valves or bovine pericardium) in heart valve replacement surgery is limited because of calcification-related failures. The mechanism of calcification of bioprosthetic valves is quite complex and has a variety of determinants, including host factors, tissue fixation conditions, and mechanical effects. Currently, there is no effective therapy to prevent calcification in clinical settings. This article reviews a variety of anticalcification strategies that are under investigation either in advanced animal models or in clinical trials. Bisphosphonates, such as ethan hydroxybisphosphonate (EHBP), inhibit calcium phosphate crystal formation. However, because of their systemic toxicity, they are used as either tissue treatments or polymeric site-specific delivery systems. Detergent treatment, such as sodium dodecyl sulfate (SDS), extracts almost all phospholipids from bioprosthetic heart valve cuspal tissue. Procedures, such as amino oleic acid pretreatment, inhibit calcium uptake. Polyurethane trileaflet valves, investigated as alternatives to bioprosthetic or mechanical valve prostheses, undergo intrinsic and thrombus-related calcification and degradation. Calcification- and thrombus-resistant polyurethanes synthesized in our laboratory by covalent linking of EHBP or heparin (either in bulk or on surface) by unique polyepoxidation chemistry are attractive candidates for further research. Tissue-engineered heart valves may have an important place in the future.