Joshi R R, Underwood T, Frautschi J R, Phillips R E, Schoen F J, Levy R J
Department of Pediatrics, University of Michigan, Ann Arbor 48109, USA.
J Biomed Mater Res. 1996 Jun;31(2):201-7. doi: 10.1002/(SICI)1097-4636(199606)31:2<201::AID-JBM6>3.0.CO;2-R.
Calcification complicates the use of the polymer polyurethane in cardiovascular implants. To date only costly experimental circulatory animal models have been useful for investigating this disease process. In this paper we report that polyurethane calcification in rat subdermal implants is enhanced by overdosing with a vitamin-D analog. The calcification-prone state, known as calciphylaxis, was induced in 4-week old rats by oral administration of a vitamin-D analog, dihydrotachysterol. We studied two commercially available polyurethanes (Biomer and Mitrathane) and two proprietary polyurethanes (PEU-2000 and PEU-100). PEU-100 is unique because it is derivatized with ethanehydroxy-bisphosphonate (EHBP) for calcification resistance. Polyurethane calcium and phosphate levels and morphological changes due to calciphylaxis were compared with those of control rat subdermal explants in 60-day studies. Increased polyurethane mineralization was observed due to calciphylaxis with 60-day rat subdermal explants of Biomer, Mitrathane, and PEU-2000 (calcium levels, respectively, 4.13 +/- 0.56, 18.61 +/- 2.73, and 3.37 +/- 0.22 microgram/mg, mean +/- standard error) as compared to control explants (calcium levels, respectively, 1.22 +/- 0.1, 12.57 +/- 0.86, and 0.20 +/- 0.86 microgram/mg). The study also demonstrated that with 60-day implants calciphylaxis had no side effects on somatic growth and serum calcium levels. Explant surface morphology of these polyurethane explants examined by scanning electron microscopy, back scattering electron imaging coupled with energy dispersive X-ray spectroscopy, and light microscopy demonstrated the presence of predominantly surface-oriented calcification. PEU-100, derivatized with 100 n.moles/ mg of EHBP, resisted calcification with explant calcium levels 0.51 +/- 0.01 (calciphylaxis) and 0.38 +/- 0.01 (control) microgram/mg. It is concluded that calciphylaxis enhances superficial polyurethane calcification in rat subdermal implants and that an EHBP-modified polyurethane resists calcification despite calciphylaxis. Rat subdermal implants using calciphylaxis may be generally useful for evaluating the calcification potential of various biomedical polymers.
钙化使聚合物聚氨酯在心血管植入物中的应用变得复杂。迄今为止，只有成本高昂的实验性循环动物模型可用于研究这种疾病过程。在本文中，我们报告了在大鼠皮下植入物中，过量使用维生素D类似物会增强聚氨酯的钙化。通过口服维生素D类似物二氢速甾醇，在4周龄大鼠中诱导出易钙化状态，即钙过敏。我们研究了两种市售聚氨酯（Biomer和Mitrathane）以及两种专利聚氨酯（PEU - 2000和PEU - 100）。PEU - 100很独特，因为它用乙烷羟基双膦酸盐（EHBP）进行了衍生化以抗钙化。在60天的研究中，将因钙过敏导致的聚氨酯钙和磷水平及形态变化与对照大鼠皮下植入物进行了比较。与对照植入物（钙水平分别为1.22±0.1、12.57±0.86和0.20±0.86微克/毫克）相比，观察到Biomer、Mitrathane和PEU - 2000的60天大鼠皮下植入物因钙过敏而导致聚氨酯矿化增加（钙水平分别为4.13±0.56、18.61±2.73和3.37±0.22微克/毫克，均值±标准误）。该研究还表明，对于60天的植入物，钙过敏对体细胞生长和血清钙水平没有副作用。通过扫描电子显微镜、背散射电子成像结合能量色散X射线光谱以及光学显微镜检查这些聚氨酯植入物的表面形态，结果表明主要存在表面取向的钙化。用100纳摩尔/毫克的EHBP衍生化的PEU - 100可抵抗钙化，植入物钙水平为0.51±0.01（钙过敏）和0.38±0.01（对照）微克/毫克。结论是，钙过敏会增强大鼠皮下植入物中表面聚氨酯的钙化，并且尽管存在钙过敏，经EHBP改性的聚氨酯仍可抵抗钙化。利用钙过敏的大鼠皮下植入物可能普遍有助于评估各种生物医学聚合物的钙化潜力。
