title: 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.
authors.affiliation: Harborview Biomechanics Laboratory, Department of Orthopedics, University of Washington, Seattle 98125, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Arm
authors.forename: A F
authors.initials: AF
authors.lastname: Tencer
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002417:Cattle; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D011108:Polymers; D019736:Prostheses and Implants; D011506:Proteins / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D011506:Proteins