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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL030035-04A1
Application #
3341049
Study Section
Oral Biology and Medicine Study Section (OBM)
Project Start
1983-08-01
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
American Dental Association Foundation
Department
Type
DUNS #
789085941
City
Chicago
State
IL
Country
United States
Zip Code
60611
Tomazic, B B (2001) Physiochemical principles of cardiovascular calcification. Z Kardiol 90 Suppl 3:68-80
Cohen, H; Solomon, V; Alferiev, I S et al. (1998) Bisphosphonates and tetracycline: experimental models for their evaluation in calcium-related disorders. Pharm Res 15:606-13
Tomazic, B B; Chow, L C; Carey, C M et al. (1997) An in vitro diffusion model for the study of calcification of bovine pericardium tissue. J Pharm Sci 86:1432-8
Skrtic, D; Eidelman, N; Golomb, G et al. (1996) In vitro inhibition of membrane-mediated calcification by novel phosphonates. Calcif Tissue Int 58:347-54
Tomazic, B B; Edwards, W D; Schoen, F J (1995) Physicochemical characterization of natural and bioprosthetic heart valve calcific deposits: implications for prevention. Ann Thorac Surg 60:S322-7
Van Gelder, J M; Breuer, E; Ornoy, A et al. (1995) Anticalcification and antiresorption effects of bisacylphosphonates. Bone 16:511-20
Tomazic, B B; Brown, W E; Schoen, F J (1994) Physicochemical properties of calcific deposits isolated from porcine bioprosthetic heart valves removed from patients following 2-13 years function. J Biomed Mater Res 28:35-47
Tomazic, B B; Brown, W E; Eanes, E D (1993) A critical evaluation of the purification of biominerals by hypochlorite treatment. J Biomed Mater Res 27:217-25
Tomazic, B B; Brown, W E; Queral, L A et al. (1988) Physiochemical characterization of cardiovascular calcified deposits. I. Isolation, purification and instrumental analysis. Atherosclerosis 69:5-19
Eidelman, N; Chow, L C; Brown, W E (1987) Calcium phosphate phase transformations in serum. Calcif Tissue Int 41:18-26

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