Chronic osteomyelitis is one of the most serious complications of orthopedic open fracture treatment. The objective of this study was to develop a biodegradable implant coating with impregnated antibiotics as an adjunct to current therapy. We used a polylactic-co-glycolic acid copolymer (PLGA) as the biodegradable carrier and gentamicin as the antibiotic. Our objectives were to establish elution characteristics of the antibiotic from the polymer, and determine if the coated orthopedic implants would inhibit bacterial growth in vitro. In the elution study, coated implants were incubated in phosphate buffered saline (PBS) at 37 degrees C and sampled daily for gentamicin levels. The in vitro model consisted of test tubes containing Mueller-Hinton culture broth inoculated with 5 x 10(6) cfu of Staphylococcus aureus and incubated at 37 degrees C. The implants were switched to a new set of inoculated tubes each day. Tubes were sampled for colony counting to determine bactericidal effects. Implant coatings consisted of 40 mg of gentamicin as a 20% mixture with PLGA. The elution curve showed an average level of 138 micrograms/mL over 15 days. This local concentration would be more than adequate to kill susceptible organisms. The in vitro study showed a significant reduction in bacterial growth in the test tubes containing coated implants. Control tubes averaged 2.5 x 10(8) cfu/mL of S.aureus over 24 days. Coated implant tubes averaged 0.9 cfu/mL. This was a reduction of greater than 99.999% (p < 0.0001). This study showed that a thin biodegradable implant coating can be developed with bactericidal activity against the organisms frequently associated with osteomyelitis in cases of open fractures.

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.