Nimni M E, Ertl D, Villanueva J, Nimni B S
University of Southern California School of Medicine, Los Angeles 90007-2697.
Am J Cardiovasc Pathol. 1990;3(3):237-45.
Calcification of collagen-derived prosthesis, such as glutaraldehyde crosslinked porcine heart valves or heart valves assembled out of bovine pericardium, presents a major clinical problem. Their subcutaneous implantation into young rats provides us with a reproducible method of assessing this form of ectopic calcification. Long-term implantation is essential, since some materials which do not calcify within the first month frequently exhibit a delayed calcific response. Crosslinked pericardium is much more likely to calcify than crosslinked tendon or reconstituted crosslinked pepsin extracted bovine type I collagen. The covalent binding of a diphosphonate to collagen and collagen-rich tissues can prevent calcification. The binding of this diphosphonate and its ability to inhibit calcification can be enhanced by increasing the number of amino groups on the collagen molecule. The degree of calcification is inversely related to the number of diphosphonate molecules covalently bound to collagen. Under standard conditions, chemical modifications appear to occur primarily on the surface of the collagen fibrils, as evidenced by the relationship between the number of molecules of APD bound and fibril diameter. The bound diphosphonate seems to interfere with crystal growth and prevent the formation of highly insoluble hydroxyapatite on the surface and interstices of the collagen fibrils.
胶原蛋白衍生假体的钙化，如戊二醛交联的猪心脏瓣膜或由牛心包组装而成的心脏瓣膜，是一个主要的临床问题。将它们皮下植入幼鼠为我们提供了一种可重复的评估这种异位钙化形式的方法。长期植入至关重要，因为一些在第一个月内未钙化的材料经常会出现延迟的钙化反应。交联心包比交联肌腱或重组交联胃蛋白酶提取的牛I型胶原更容易钙化。双膦酸盐与胶原蛋白和富含胶原蛋白的组织的共价结合可以防止钙化。通过增加胶原蛋白分子上氨基的数量，可以增强这种双膦酸盐的结合及其抑制钙化的能力。钙化程度与共价结合到胶原蛋白上的双膦酸盐分子数量成反比。在标准条件下，化学修饰似乎主要发生在胶原纤维的表面，这由结合的APD分子数量与纤维直径之间的关系证明。结合的双膦酸盐似乎会干扰晶体生长，并防止在胶原纤维的表面和间隙形成高度不溶性的羟基磷灰石。
