Biostability and Biocompatibility of Modified Polyurethane Elastomers

Several strategies have been employed to increase the biostability of medical grade polyurethanes while maintaining the desirable properties of current poly(ether urethanes). It was hypothesized that polyurethane surface chemistry controls biodegradation/biostability that can lead to ultimate failure/success of these materials in clinical applications. Chemical modification or replacement of the susceptible soft segment was evaluated as a design strategy to increase the biostability of medical grade polyurethanes. The effect of soft segment chemistry on the phase morphology, mechanical properties and in vivo response of commercial polyurethanes were compared. Poly(ether urethane) (PEU), silicone-modified poly(ether urethane) (PEU-S), poly(carbonate urethane) (PCU) and silicone-modified poly(carbonate urethane) (PCU-S) elastomers were investigated. AFM phase imaging indicated that the overall two-phase morphology of poly(ether urethanes), necessary for its thermoplastic elastomeric properties, was not disrupted by changing the soft segment chemistry. All of the polyurethanes exhibited thermoplastic elastomeric behavior similar to that of the poly(ether urethane). Following material characterization, the biocompatibility of the polyurethane elastomers was evaluated using a subcutaneous cage implant protocol. All of the polyurethanes tested retained the excellent biocompatibility typical of poly(ether urethane) elastomers. Overall, the candidate polyurethanes were concluded to be suitable replacements of current poly(ether urethane) elastomers in medical applications. The results from the cage implant study and cell culture experiments indicated that monocytes adhere, differentiate and fuse to form foreign body giant cells (FBGCs) on all of the polyurethane specimens. It is now generally accepted that the reactive oxygen species released by these adherent macrophages and FBGCs initiate PEU biodegradation. ATR-FTIR analysis of explanted samples provided evidence of chain scission and crosslinking in all of the polyurethane specimens. Therefore, it was concluded that the chosen soft segment modifications were insufficient to fully inhibit biodegradation. Potential biodegradation mechanisms were explored using oxidative and hydrolytic enzyme systems. An oxidative solution of 20% hydrogen peroxide/0.1 M cobalt chloride was shown to reproduce and accelerate the biodegradation. Characterization with ATR FTIR and SEM revealed soft segment and hard segment degradation consistent with the chemical changes observed after long term in vivo treatment. The observed in vivo and in vitro degradation was inhibited by adding an antioxidant to the PEU and PCU films. Treatment of PEU and PCU with high concentrations of cholesterol esterase resulted in minimal degradation after 36 days. It was concluded that although the enzyme initiated polyurethane degradation, the effect was minimal compared to the oxidation of these polyurethane elastomers. These results supported oxidation as the dominant mechanism of biodegradation of PEU and PCU. The silicone modification did not alter the oxidative mechanism of PEU and PCU biodegradation. Characterization of the type and extent of surface degradation of candidate polyurethanes after in vitro and in vivo exposure was used to develop predictive correlations between polyurethane chemistry and biodegradation. The H2O2/CoCl2 system was used to accelerate oxidative biodegradation to predict long-term biostability in quantitative comparison with current clinical poly(ether urethanes). The rate of PCU degradation was significantly reduced and the degraded surface layer was much thinner compared to PEU. In addition, the degraded surface layer buckled with applied stress as opposed to the cracking observed in PEU. Environmental stress cracking has been reported as the primary failure mechanism of poly(ether urethanes) in medical devices. Therefore, the clinical relevance of these findings to poly(carbonate urethane) l