This proposal is directed to understanding the mechanisms related to calcium deposition on biopolymers in cardiac assist devices. Calcification of these implants compromises their long term successful use. Our previous studies, of explanted left ventricular assist devices in bovine have defined certain contributing factors which promote calcium deposition related to a) the mechanics of the pump, b) the characteristics of the biomaterial (surface and blood interactions) and c) the physiologic status of the animal. It has been hypothesized that initiation of the calcification process is related to the formation of thrombus, the degeneration of cells, and the accumulation of calcium binding proteins. However, we have evidence that certain of these calcium binding proteins in plaque appear to have an important physiologic role in recruiting macrophage and mineral resorbing cells. In this renewal application, we will use an in vitro flexure device model which accommodates 6 discs to test these hypotheses. The altered metabolism of monocytes, macrophages, fibroblasts and endothelial cells grown synthetic polyurethanes used in cardiac assist devices (Angioflex, Biomer and Tecoflex) with smooth and textured surfaces (Biomer fibrils or Dacron flocking) will be studied. These cell populations have been selected because of their association with pseudointima formation on assist device implants. Cellular degeneration with subsequent calcification will be examined as a function of surface properties and mechanical strain. The calcium binding proteins we have identified accumulating in pathologic calcific deposits, will be examined quantitatively as chemoattractants for phagocytic cells involved in the resorption/degradation of pathologic calcific deposits in vivo using a model of subcutaneous implantation of plaque in rats and in vitro by measuring calcium solubilization of plaque by monocytes. These studies will provide insight to understanding the limitations of cells on a cardiac assist device, as related to both initiation of calcification and the inability of cells to biologically degrade or resorb plaque.
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