Antioxidant inhibition of poly(carbonate urethane) in vivo biodegradation

Abstract

This study compared the effect of an antioxidant on the in vivo biodegradation of a poly(carbonate urethane) (PCU) and a poly(ether urethane) (PEU). Unstrained PEU and PCU films with and without Santowhite were implanted subcutaneously into 3-month-old Sprague-Dawley rats for 3, 6, and 12 months. Characterization of unstabilized PEU and PCU with ATR-FTIR and SEM showed soft-segment and hard-segment degradation consistent with previous studies. In particular, evidence of chain scission and crosslinking of the surface was present in the ATR-FTIR spectra of explanted specimens. Addition of 2.2 wt % antioxidant inhibited the in vivo degradation of both PCU and PEU. Although the antioxidant probably improved polyurethane biostability by decreasing the susceptibility of the polymer to degradation, modulation of the cellular response to prevent the release of degradative agents was also possible. To differentiate the effects, the foreign-body response was investigated with the use of a standard cage implant protocol. Polyurethane films were implanted in wire mesh cages subcutaneously in rats for 4, 7, and 21 days. There were no statistical differences among materials in the inflammatory exudate cell counts, adherent cell densities, or percent fusion of macrophages into foreign-body giant cells (FBGCs). Therefore, it was concluded that the antioxidant inhibited degradation by capturing oxygen radicals that would otherwise cause polyurethane chain scission and crosslinking.

Foreign body reaction to biomaterials

“…The soft segment of polyether polyurethanes is known to undergo degradation. [86][87][88][89][90][91][92][93][94][95][96][97][98] This phenomenon will be discussed in the next section.…”

“…Polycarbonates were used as the soft segments in these polymers and exhibited a marked reduction in degradation. [96] A fourth generation of polyurethanes is currently under investigation. These polyurethanes have soft segments that are either polyether or polycarbonate but, more importantly, have short chain molecules attached to the polymer chain ends (SME, surface modifying endgroups) such that when fabricated, these adhesion inhibiting molecules are present at the surface of the biomaterial at the tissue/material interface.…”

A systems approach to modeling drug release from polymer microspheres to accelerate in vitro to in vivo translation

“…Furthermore, we would expect to see slowed in vivo release kinetics through suppression of ROS via antioxidants or other means. In fact, a number of studies 59,42,60,5 have shown decreased in vivo degradation of biodegradable polymers through the delivery of antioxidants to the local implant site. This particular study set has not been replicated herein due to the need to retrospectively fit the ROS suppression kinetics as a function of antioxidant concentration and reactivity with ROS.…”

The use of CD47-modified biomaterials to mitigate the immune response

“…[83][84][85][86] With respect to pacemaker leads, which commonly use polyurethane insulation, the duration from implantation to device failure has been shown to be as short as $2.5 years. 87 Laboratories, including our own, have tried to address the issue of oxidative degradation of polyurethane by coblending 84 or covalently linking 86,88 phenol-based antioxidants to polyurethane preparations. The limitations of this approach lie primarily in the fact that the antioxidants are expended once they react with hydroxy radicals.…”