Effects of cyclical mechanical stress on the controlled release of proteins from a biodegradable polymer implant

Abstract

The availability of osteogenic proteins for orthopedic applications has led to great interest in developing delivery systems for these substances. Standard release rate models are applicable in most biological settings, but orthopedic implants usually bear mechanical loads. To determine whether a release rate model for load bearing applications must consider mechanical stress, the effects of dynamic mechanical stress on the in vitro release kinetics of two model proteins, bovine albumin (BA) and trypsin inhibitor (TI), from a biodegradable film were evaluated. Biodegradable poly(lacticco-glycolic acid) cylindrical implants 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 polymer carrier were evaluated. Cumulative BA and TI releases with time were significantly higher when a cyclic bending load was applied and increased with the magnitude of the load. Mass loss was not significantly 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 roughly circular. This implies that the pores probably act as stress risers to initiate cracks, which then expose more surface area, increasing protein release.

The Effects of Dynamic Compressive Loading on Biodegradable Implants of 50–50% Polylactic Acid–Polyglycolic Acid

“…15 However, cyclic flexural loading was shown to have a significant effect on the protein release characteristics of such a copolymer. 16 In addition, a dynamic flexural load was shown to have a significant effect on the degradation of mechanical properties of poly(ortho)esters. 17 The PLA-PGA families have been widely used for fabricating implantable devices and have proven to be relatively biocompatible.…”

Effects of external stress on biodegradable orthopedic materials: A review

“… PLLA [91] Tension 1 Hz A faster degradation under load condition. 50:50 PLGA [92] Bending 0.4 Hz No significant influence on mass loss and molecular weight. …”

Mechanoresponsive materials for drug delivery: Harnessing forces for controlled release

“…Arm et al [124] describe the release of bovine albumin or trypsin inhibitor under cyclic tensile stress from poly(lactic- co -glycolic acid) [PLGA] thin film depots wrapped around poly- p -dioxanone cylindrical implants. Using cyclic three-point bending (0.4 Hz (30 mins/ day) for 2 weeks at 0 mm, 0.5 mm, or 1 mm deflections) as a model for loading in long bones, the authors demonstrate faster release rates with larger deflections.…”