EFFECTS OF CYCLICAL MECHANICAL-STRESS ON THE CONTROLLED-RELEASE OF PROTEINS FROM A BIODEGRADABLE POLYMER IMPLANT

The availability of osteogenic proteins for orthopedic applications ha s led to great interest in developing delivery systems for these subst ances. Standard release rate models are applicable in most biological settings, but orthopedic implants usually bear mechanical loads. To de termine whether a release rate model for load bearing applications mus t consider mechanical stress, the effects of dynamic mechanical stress on the in vitro release kinetics of two model proteins, bovine albumi n (BA) and trypsin inhibitor (TI), from a biodegradable film were eval uated. Biodegradable poly(lactic-co-glycolic acid) cylindrical implant s with embedded proteins were subjected to cyclic three point bending loading of 720 cycles/day at 0.4 Hz for 2 weeks. Protein release into solution swelling and mass loss changes, molecular weight degradation, and the presence of microstructural stress cracks and pores in the po lymer carrier were evaluated. Cumulative BA and TI releases with time were significantly higher when a cyclic bending load was applied and i ncreased with the magnitude of the load. Mass loss was not significant ly greater, nor was swelling or molecular weight change of the polymer carrier in this 2-week interval. Pores on the surface of the polymer in the highest stress region were elongated into cracks, compared with pores in the low-stress region of the same implant, which were roughl y circular. This implies that the pores probably act as stress risers to initiate cracks, which then expose more surface area, increasing pr otein release. (C) 1997 John Wiley & Sons, Inc.