Development and application of bone morphogenetic proteins for the enhancement of bone healing

Bone morphogenetic proteins are multifunctional cytokines and members of the transforming growth factor-beta superfamily. They include the only signaling molecules that can singly induce de novo bone formation at orthotopic and heterotopic sites. Their osteoinductive potency and ability to enhance or accelerate bone healing has been demonstrated in animal models of human orthopedic injuries and diseases, and in human clinical orthopedic patients. Recombinant human bone morphogenetic proteins 2 and 7 have recently received the approval of regulatory agencies for the clinical treatment of selected human acute long bone fractures and nonunions, as well as lumbar fusion. It is likely that additional indications will be approved as supportive data for the proteins' efficacy in the treatment of specific orthopedic conditions are generated. In addition to the type I collagen presently being used clinically as a locally implantable delivery vehicle for bone morphogenetic proteins, mineral, synthetic polymer, and extracellular matrix components continue to be tested as alternative matrices. Other means of bone morphogenetic protein delivery undergoing preliminary evaluation include gene transfer therapy and systemic administration.