On the transplantation, regeneration and induction of bone: The path to bone morphogenetic proteins and other skeletal growth factors

The clinical and experimental transplantation of bone dates back to the seventeenth century and human allogeneic (homogeneic) bone has been successfully used as an alternative to autogenous bone since 1878, when Sir William Macewen reconstructed the right humerus of William Connell. This review describes how subsequent studies of bone transplantation led to the eventual discovery of a new family of secreted signalling molecules — the bone morphogenetic proteins (BMPs), and the realisation of the important role of polypeptide growth factors in mediating the growth, remodelling and regeneration of the skeleton. The development of suitable alternatives to both autogenous and allogeneic bone has been a goal of bone and biomaterials research for more than 30 years. The first requirement is a biocompatible, bioresorbable, osteoconductive framework supporting the ingrowth of host cells from the recipient bed. Many materials including collagen, calcium phosphate ceramics and synthetic polymers have been widely tested experimentally with varying success. The discovery of osteoinductive BMPs and their availability in recombinant human forms has given considerable impetus to the field. However, progress to date in engineering significant quantities of functional bone tissue in vivo has been disappointing; finding suitable carriers for BMPs has proven to be a greater challenge than expected. The dilemma for the clinician and the biotechnology industry, at present, is that, while recombinant human growth factors are readily available for clinical use, the lack of delivery systems that can adequately mimic both the physical properties and release kinetics of bone matrix remains a major handicap.