Abstract
Infection is a common complication of severe open fractures and compromises bone healing. The present standard of care is a two-stage approach comprising of initial placement of antibiotic-impregnated PMMA beads to control infection followed later by bone grafting. Although the systemic antibiotics and PMMA/antibiotic beads control the infection initially, there are often residual bacteria within the wound. After grafting and definitive closure, the implanted graft is placed in an avascular defect and could function as a nidus for infection. Bioactive porous polyurethane (PUR) scaffolds have been shown to improve bone healing by delivering recombinant human bone morphogenetic protein-2 (BMP-2) and reduce infection by delivering antibiotics. The release kinetics of the BMP-2 were an initial burst to recruit cells and sustained release to induce the migrating cells. The Vancomycin (Vanc) release kinetics were designed to protect the graft from contamination until vascularisation by having an initial burst and then remaining over the MIC for Staph. aueus for two months. In this study, PUR+BMP-2+Vanc scaffolds were first tested in a non-infected critical size rat femoral segmental defect and was found to perform comparably to PUR+BMP-2, thus indicating that Vanc did not hinder bone healing. PUR+BMP-2+Vanc scaffolds were subsequently evaluated in an infected critical size rat femoral segmental defect. The dual delivery approach resulted in significantly more new bone formation and infection control than both PUR+BMP-2 and the collagen+BMP-2 treatments. These data indicate that the dual-delivery strategy effectively protects the graft from infection during wound healing and regenerates more bone in contaminated defects. This moderately osteoconductive bone graft is capable of being injected, provides a more sustained release of BMP-2 than the collagen sponge, and can release antibiotics for over 8 weeks. The dual-delivery approach may improve patient outcomes of open fractures by protecting the osteoinductive graft from colonization until vascularization occurs.
