Biomimetic Hematoma as a Novel Delivery Vehicle for rhBMP-2 to Potentiate the Healing of Nonunions and Bone Defects.

The management of bone defects and nonunions creates unique clinical challenges. Current treatment alternatives are often insufficient and frequently require multiple surgeries. One promising option is bone morphogenetic protein-2 (BMP-2), which is the most potent inducer of osteogenesis. However, its use is associated with many side effects, related to the delivery and high doses necessary. To address this need, we developed an ex vivo biomimetic hematoma (BH), replicating naturally healing fracture hematoma, using whole blood and the natural coagulants calcium and thrombin. It is an autologous carrier able to deliver reduced doses of rhBMP-2 to enhance bone healing for complex fractures. More than 50 challenging cases involving recalcitrant nonunions and bone defects have already been treated using the BH delivering reduced doses of rhBMP-2, to evaluate both the safety and efficacy. Preliminary data suggest the BH is currently the only clinically used carrier able to effectively deliver reduced doses (∼70% less) of rhBMP-2 with high efficiency, rapidly and robustly initiating the bone repair cascade to successfully reconstruct complex bone injuries without side effects. The presented case provides a clear demonstration of this technology's ability to significantly alter the clinical outcome in extremely challenging scenarios where other treatment options have failed or are considered unsuitable. A favorable safety profile would portend considerable promise for BH as an alternative to bone grafts and substitutes. Although further studies regarding its clinical efficacy are still warranted, this novel approach nevertheless has tremendous potential as a favorable treatment option for bone defects, open fractures, and recalcitrant nonunions.