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.