Growth factors and bone regeneration. Implications of barrier membranes

Insufficient or absence of bone healing is a frequent problem within all surgical fields. This often necessitates treatment by autogenous bone grafting. Recently, two new techniques to promote bone healing were introduced, the osteopromotive membrane technique, and local delivery of growth-stimulatory factors, both with a high rate of success in preclinical experiments. The aims of the present series of investigations were to further develop the membrane barrier technique, both by itself as well as in combination with local delivery of growth factors, in animal experiments. During membrane-promoted bone formation, the membrane porosity was found to be of importance for the initial rate of bone formation as well as for the performance of the material in the tissue. In contrast, the final amount of bone was not affected. In a well-known bone healing model, the 5 mm in diameter 'critical size defect' at the rat mandibular ramus, the efficacy of rhBMP-2, rhTGF-beta 1 and rhFGF-2 to promote bone regeneration alone and in combination with barrier membranes was evaluated. Under both conditions, rhBMP-2 was found to be an efficient promoter of bone healing. rhFGF-2 had some stimulatory effect both with and without barrier membranes, whereas rhTGF-beta 1 was found to have a minor stimulatory effect by itself, but in combination with barrier membranes it was inhibitory. These observations were interpreted as being the result of an effect of the growth factors at different levels of the osteoblastic lineage; rhBMP-2 being an inducer of osteoblastic cells from stem cells, whereas rhTGF-beta 1 may primarily act on already committed cells. In contrast, rhFGF-2 may have stimulatory effect at different levels of the lineage. Based on the positive results obtained by the combination of rhBMP-2 and barrier membranes in the rat mandible, this combination was then applied to (i) rabbit radius defects; and (ii) a rat calvarial osteoneogenesis model. In the long bone model, membranes by themselves were insufficient to promote bone healing, but the combination resulted in complete regeneration. In the osteoneogenesis model, the combination of barrier membranes and rhBMP-2 resulted in a 100% increase in the final amount of achievable bone. In the last study, rhFGF-2 (no barrier membranes) was shown to enhance revitalization of autoclaved autogenous bone grafts, a procedure clinically used in craniofacial reconstruction mainly after tumor surgery. The combined use of rhBMP-2 and barrier membranes has great potential to be a useful treatment for improving bone healing and might be an alternative to bone grafting.