The physical and chemical factors at the blood-biomaterial interface which cause calcium phosphates to precipitate on cardiovascular implants will be investigated to: I. Characterize cardiovascular calcifications chemically and physically to establish crystal growth mechansisms. In particular, we will seek to determine if """"""""amorphous calcium phosphate"""""""" (ACP), brushite, and/or octacalcium phosphate (OCP) have acted as precursors in the formation of hydroxyapatite present in these calcifications. II. Establish levels of saturation of serum and blood with respect to various sparingly soluble calcium phosphates. The degrees of saturation of serum with respect to CaHPO4, CaHPO4.2H2O, Ca8H2(PO4)6.5H2O, Beta-Ca3(PO4)2, and Ca5(PO4)3 (OH) will be measured through use of equilibration experiments. These results will be compared with those obtained in the studies of crystal-growth mechanisms. III. Apply experimental kinetic models to establish factors governing crystal formation: Two types of kinetic models will be employed: (1) the constant composition technique of Nancollas; (2) the procedure for studying ACP transition (ACP arrow OCP arrow OHAp), as modified by Tung, to distinguish between rates of formation of OCP and hydrolysis of OCP to OHAp. IV. Characterize the chemical and physical properties of the natural and synthetic materials commonly used as implants being studied in our experiments: Special attention will be focused on the changes induced in the surface produced by flexing or exposure to blood or serum, and calcification. V. Apply thermodynamic considerations and experiments to determine the effects of surface charges on precipitate formation: The phase diagram will be examined to determine how it is modified by flow of a saturated solution onto a charge surface. In these ways basic information will be obtained which will facilitate (i) development of implant materials which do not calcify; (ii) treatments which prevent calcification; and (iii) formulation of a standardized test for calcifiability of cardiovascular implant materials.
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