Biodegradable Polyurethane Scaffolds and Delivery Systems for Regeneration of Bone Tissue

Abstract

Infection is a common complication in open fractures that compromises bone healing. Currently, the clinical standard care for treating contaminated open fractures comprises a staged approach, wherein the wound is first treated with antibiotic-laden PMMA beads to control the infection followed by bone grafting. However, the non-biodegradable PMMA must be removed during an extra surgical step. While complications may also arise from the wound healing process, it is critical to control infection in the graft as well. In this Ph.D. dissertation, I aimed to combine both steps in the traditional treatment to allow both infection control and wound healing to occur simultaneously, which has been achieved by delivering both vancomycin (an antibiotic) and bone morphogenetic protein (rhBMP-2, a morphogen growth factor) from biodegradable porous polyurethane composite scaffolds. Porous polyurethane scaffolds were synthesized from a two-component reaction between polyester triol and triisocyanate with desired mechanical properties and degradation kinetics. The drugs were incorporated within the scaffolds as well, and the release rates were tuned to the biological requirements of the clinical indication. Through the PLGA microencapsulation approach to control the release of rhBMP-2, we found that both burst release as well as sustained release is desired to optimize bone regeneration in rat femoral defects. The effective therapeutic concentration release of vancomycin was sustained for up to at least 8 weeks by transferring commercially available vancomycin hydrochloride to vancomycin free base that has significantly decreased solubility, which translated to better infection control in an infected rat femoral segmental defect. The polymer composites containing both rhBMP-2 and vancomycin free base were then tested in an infected rat femoral segmental defect. The prolonged release of antibiotic controls infection, allowing bone healing process to occur which was accelerated by the sustained release of rhBMP-2. The strategy of protecting the graft from infection during wound healing eliminates an extra surgical removal step in current clinical standard care, and presents a potentially significant innovation in clinical treatment of infected bone wounds.