Osteoinductive biodegradable intramedullary implant accelerates bone healing and mitigates complications in a rat bone transport model

Bone transport distraction osteogenesis (DO) is one of the most successful surgery-driven endogenous tissue regeneration approaches for the treatment of large bone defects. However, prolonged consolidation, docking site nonunion, and pin tract infection remain challenging complications. Here, we engineered an osteoinductive, biodegradable intramedullary (IM) implant for sustained release of bone morphogenetic protein-2 (BMP-2) as an adjunctive therapy of bone transport to address the clinical challenges. A hybrid tissue engineering construct (HyTEC) technique was developed to enable sustained release of BMP-2 in a broad range. 100% bony fusion was achieved in the IM implants incorporating with 2 μg and 6 μg BMP-2 as early as 34 days after bone transport surgeries in the management of 8-mm femoral defect. Load bearing was restored 55 days after surgeries when the fixator was removed. Eluting BMP-2 from the IM implants accelerates bone formation and angiogenesis at early phase, and increase mineralization at late phase, especially at the docking sites, leading to early bony bridging. Moreover, no pin tract infection but seamless integration could be found in the 2 μg and 6 μg BMP-2 treated groups. Surgical control and IM implant showed high proportion of non-union and pin tract infections. 2 μg BMP-2 delivered by collagen sponge or 0.5 μg BMP-2-laden IM implant did not induce bone regeneration effectively, resulting in some non-unions and infections. A presence of bacteria of fecal origin in the infection sites was identified. In conclusion, this osteoinductive IM implant holds great promise in revolutionizing bone transport DO technique in the management of bone defect by accelerating bone regeneration and mitigating complications. 8 mm bone defect and 4 mm segmental bone was created in rat femurs. Then rats were divided into three groups. For rats in control group, segmental bone was placed in the middle of defect site. Distraction osteogenesis and BMP2-eluting implant was not used for these rats. Rats in blank group received distraction ostegenesis without BMP2-eluting implant. Rats in BMP2 group received distraction osteogenesis with BMP-2 eluting implant.