Large bone defects, congenital or caused by diseases, trauma or surgery, do not heal spontaneously and are usually a clinical challenge in the orthopedic and dental practices. A critical review concerning strategies to substitute lost bone or stimulate osteogenesis was undertaken. Pivotal concepts ranging from traditional bone grafting and use of biomaterials to local application of growth factors and gene therapy were addressed, including critical comments on the efficacy and safety, difficulties, advantages and disadvantages of each method. The most predictable results are still obtained with autogenous bone graft, despite the inconveniences of morbidity and limited availability of graft material. Satisfactory results have been reported for recombinant bone morphogenetic proteins (rhBMPs)-2 and -7, which distinguish for their osteoinductive property, the difficulty being the need for a degradable carrier that allows its continuous release in a rate compatible to that of new bone formation. Other bone growth factors are currently under evaluation in preclinical models of bone defects; however their efficacy is also dependent on the competence of a delivery strategy and on an appropriate delineation of "which one", "which dose" and "when". Parameters of efficiency and safety for gene therapy are still being established. In conclusion, given the variety of growth factors involved in the complex cascade of bone repair and the biological interactions between them, it remains a challenge to accomplish the ideal strategy to stimulate reparational bone formation in specific conditions of the medical as in the dental practices.

Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes that degrade extracellular matrix components, facilitating cell migration and tissue remodeling. MMPs secreted by osteclasts are important in the physiological bone resorption as in pathological bone degradation. However, the essentially bone absorbing hole of MMPs, particularly of the MMP-2, has been questioned in recent years by studies that show its importance in osteoblastic cells differentiation and in vitro bone formation. Therefore, the MMP-2 may have also an important hole in reparational bone formation. The purpose of the present study was to investigate the pretense osteostimulatory effect of the rhMMP-2 linked to monoolein (used as a carrier) implanted into rat calvarial defects. Bone defects of 4mm in diameter were created unilaterally in rats calvaria and filled with natural blood clot (control), monoolein or rhMMP-2 linked to monoolein. The animals were killed 2 and 4 weeks postoperatively and the rate of new bone formation was estimated in histological sections by a histometric differential point-counting method. The rate of reparational bone formation was similar in the animals from control and monoolein groups and was significantly greater in the MMP-2 group, in both periods. From the results it may be concluded that monoolein did not interfere with the reparacional process and seemed effective as a rhMMP-2 carrier. In addition, the results add evidence to the importance of MMP-2 activity for bone formation, in an in vivo bone healing experimental model.