| Tyrosine-derived polycarbonates were employed as a platform technology for the discovery of optimal resorbable stent materials. Among the polymers, poly(DTE carbonate) has shown excellent biocompatibility in hard tissue applications. However, its properties were not optimized for vascular applications. Several structural modifications were therefore implemented to incorporate carboxylate side groups for tunable degradation, iodination for increased radiopactiy, and PEG bocks for tailored bulk and surface properties. The discovery of DTtB and I2DTtB led to an appropriate acidolysis deprotection methodology for carboxylate side group synthesis, which made it possible to combine all three structural modifications into one polymer, The result was a focused library of polymers represented by the following design formula: Poly(I 2DTE-co-x%I2DT-co-y%PEG2000carbonate), where "x" was 10, 15, and 20% and "y" was 1, 2.5, and 4%. This test matrix of nine polymers was used to examine how small changes in the polymer structure affected the polymer's utility as a cardiovascular stent material.; Bulk and surface properties were characterized and the interplay between I2DT and PEG2000 was examined. A one-year in vitro degradation study was conducted to pinpoint formulations that would maintain structural integrity in a time frame analogous to vessel healing post stenting. Radiographs of polymer films fabricated into stents by REVA Medical, Inc. demonstrated clinically sufficient radiopacity compared to steel control stents when implanted into pig coronary arteries. Polymer sequence distribution was determined to be statistically random for these iodinated and PEG-containing polycarbonates. Collectively, the data showed that the novel materials design strategy employed was useful in the rapid discovery of optimal materials for use in resorbable polymeric stents. |
