Biomimetic hematoma delivers an ultra-low dose of rhBMP-2 to successfully regenerate large femoral bone defects in rats

Successful repair of large bone defects remains a clinical challenge. Following fractures, a bridging hematoma immediately forms as a crucial step that initiates bone healing. In larger bone defects the micro-architecture and biological properties of this hematoma are compromised, and spontaneous union cannot occur. To address this need, we developed an ex vivo Biomimetic Hematoma that resembles naturally healing fracture hematoma, using whole blood and the natural coagulants calcium and thrombin, as an autologous delivery vehicle for a very reduced dose of rhBMP-2. When implanted into a rat femoral large defect model, complete and consistent bone regeneration with superior bone quality was achieved with 10-20× less rhBMP-2 compared to that required with the collagen sponges currently used. Moreover, calcium and rhBMP-2 demonstrated a synergistic effect enhancing osteogenic differentiation, and fully restored mechanical strength 8 weeks after surgery. Collectively, these findings suggest the Biomimetic Hematoma provides a natural reservoir for rhBMP-2, and that retention of the protein within the scaffold rather than its sustained release might be responsible for more robust and rapid bone healing. Clinically, this new implant, using FDA-approved components, would not only reduce the risk of adverse events associated with BMPs, but also decrease treatment costs and nonunion rates.