Local delivery of tobramycin from injectable biodegradable polyurethane scaffolds

Infections often compromise the healing of open fractures. While local antibiotic delivery from PMMA beads is an established clinical treatment of infected fractures, surgical removal of the beads is required before implanting a bone graft. A more ideal therapy would comprise a scaffold and antibiotic delivery system administered in one procedure. Biodegradable polyurethane (PUR) scaffolds have been shown in previous studies to promote new bone formation in vivo, but their potential to control infection through release of antibiotics has not been investigated. In this study, injectable PUR scaffolds incorporating tobramycin were prepared by reactive liquid molding. Scaffolds had compressive moduli of 15-115 kPa and porosities ranging from 85-93%. Tobramycin release was characterized by a 45-95% burst (tuned by the addition of PEG), followed by up to 2 weeks of sustained release, with total release 4-5-times greater than equivalent volumes of PMMA beads. Released tobramycin remained biologically active against Staphylococcus aureus, as verified by Kirby-Bauer assays. Similar results were observed for the antibiotics colistin and tigecycline. The versatility of the materials, as well as their potential for injection and controlled release, may present promising opportunities for new therapies for healing of infected wounds.