Neutrophil-mediated degradation of segmented polyurethanes

The biostability of polyurethanes was evaluated using a human neutrophil cell culture. The polymers were synthesized with 14C radiolabelled components incorporated into the polyurethane chain and the amount of radiolabel released during exposure to cells and medium was used as a marker for material degradation. The effect of diisocyanate, soft segment and chain extender chemistry on the susceptibility of polymer degradation was examined. All polymers showed a release of material into the tissue culture medium which was unrelated to the cells. A significant cell-dependent release of radiolabel-containing material was found from one of the polymers (a polyester urea-urethane, TDI/ PCL/ED) which increased linearly up to 96 h. The polyether-containing polyurethanes showed no significant cell-mediated degradation under similar conditions as measured by radiolabel release. Scanning electron microscopy (SEM) showed that the cells adhered to the different polyurethanes. However, no effect of neutrophils on polymer structure could be detected by this technique. The cellular response to each polymer was evaluated by measuring release of elastase-like activity (ELA) into the tissue culture media. After 24 h TDI/PCL/ED showed the highest levels of ELA in the tissue culture medium. When TDI/PCL/ED was incubated with commercial elastase in vitro, a significant release of radiolabel was found which was comparable to the amount of radiolabelled material released from this polymer in contact with the neutrophils in culture. No significant amount of radiolabel was released from the corresponding polyether material (TDI/PTMO/ED) under similar conditions. This study has identified one enzymatic activity (elastase) as a possible contributor to the deterioration of biomedical implants in vivo in that the polymer which elicited the greatest response of ELA also showed release of radiolabel when incubated with elastase in vitro. The use of a live cell culture system to assess the susceptibility of polyurethanes to degradation has provided a significant step forward in understanding the mechanism of biodegradation.