Biomaterial-associated calcification: pathology, mechanisms, and strategies for prevention.
Deposition of calcium-containing apatite mineral occurs widely in association with cardiovascular and noncardiovascular medical devices and biomaterials, is the leading cause of failure of contemporary bioprosthetic heart valves, and limits the functional lifetime of experimental (and potentially clinical) mechanical blood pumps and polymeric heart valves. Calcification of bioprosthetic tissue is primarily intrinsic, related to cuspal connective tissue cells and fragments, and collagen. In contrast, the predominant site of calcific crystals on flexing polymeric surfaces in blood pumps or valve prostheses is extrinsic, associated with adherent cells, thrombus, or pseudointima. Pathologic calcification shares key features with physiologic skeletal mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. This suggests a unified hypothesis for normal and abnormal mineralization. Several approaches are being studied experimentally for the inhibition of bioprosthetic heart valve calcification. Controlled-release diphosphonate therapy, perhaps in conjunction with an anticalcification cuspal pretreatment, appears most effective. Research objectives in biomaterial-associated calcification include (1) development of animal models, (2) determination of initial crystal nucleation events and sites, (3) elucidation of the relative roles of host, implant, and mechanical determinants, and (4) development of approaches for the inhibition of mineralization.
Schoen
F J
FJ
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
Harasaki
H
H
Kim
K M
KM
Anderson
H C
HC
Levy
R J
RJ
D001243:Assisted Circulation / Q000009:adverse effects*; D001672:Biocompatible Materials / Q000009:adverse effects; D001705:Bioprosthesis / Q000009:adverse effects*; D002114:Calcinosis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006353:Heart-Assist Devices / Q000009:adverse effects*
D001672:Biocompatible Materials