Union of a chronically infected internally stabilized segmental defect in the rat femur after debridement and application of rhBMP-2 and systemic antibiotic

Objectives: The goal of this study was to determine whether recombinant human bone morphogenetic protein-2 (rhBMP-2) would induce new bone fomation in an internally stabilized segmental defect with a chronic bacterial infection in the rat femur and whether treatment with systemic antibiotic would enhance this effect. Methods: A 6-mm unilateral femoral segmental defect was surgically created in 120 Sprague-Dawley rats, internally stabilized with a polyacetyl plate and 6 Kirschner wires, and contaminated with 104 colony-forming units of Staphylococcus aureus. After 2 weeks, all defects were surgically debrided and implanted with 0, 20, or 200 mu g of rhBMP-2 in a type I bovine collagen sponge. Half of the animals in each treatment group received 4 weeks of systemic antibiotic, and half did not. Animals were euthanized at 4 or 12 weeks after debridement. Bone formation within and adjacent to the defect was assessed using microcomputed tomography, torsional failure testing and undecalcified histology. Results: No substantial callus formed in the infected defects without rhBMP-2. Significantly more mineralized callus was induced with the higher dose of rhBMP-2 than with the lower dose (P=0.001, with systemic antibiotic therapy than without (P < 0.001), and at 12 weeks after debridement compared with 4 weeks (P < 0.001). Conclusions: Recombinant human bone morphogenetic protein-2 maintained its osteoinductive capability in the presence of a chronic infection, and this property was enhanced by systemic antibiotic. This study presents an intervention that may potentially accelerate fracture healing in the presence of infection and colonized hardware, thereby permitting earlier removal of the hardware, and more timely and effective treatment of infection.