Evaluation of a polymeric composite bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

Abstract

We previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane (dPU), nano-sized hydroxyapatite (nHA), and decellularized bovine bone particles (DBP). In this report we describe the results of studies aimed at evaluating the use of this scaffold as a means of local antibiotic delivery for the prevention of infection in a segmental bone defect contaminated with Staphylococcus aureus. We evaluated two different scaffold formulations that contained the same components in the same ratios but differed from each other with respect to overall porosity and therefore surface area. Studies done with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity was correlated with increased uptake and prolonged release of all three antibiotics. Vancomycin could be passively loaded into either scaffold formulation in an amount sufficient to prevent infection, as evidenced by the complete eradication of viable bacteria from the surgical site of most animals in a rabbit model of a contaminated mid-radial segmental bone defect. Even in those few cases in which complete eradication was not achieved, the number of viable bacteria present in the bone was significantly reduced comparison to untreated controls. There was also no radiographic evidence of osteomyelitis in any rabbit treated with vancomycin-loaded scaffold. Microcomputed tomography (CT) of bone defects up to 84 days of exposure to scaffolds with and without vancomycin also demonstrated that the addition of vancomycin even in the highest concentration did not significantly diminish the osteogenic properties of either scaffold formulation. Together, these results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery.