Factors that modulate the effects of bone morphogenetic protein-induced periodontal regeneration: a critical review

The healing process initiated by a single molecular species of bone morphogenetic protein (BMP) such as BMP-2 or BMP-7 sets in motion a cascade of cellular events resulting in differentiation of progenitor cells into phenotypes involved in periodontal regeneration. For example, animal studies show that a single dose of recombinant human (rh) BMP-2 increases the rate of normal intramembranous bone formation and enhanced cementum formation during periodontal wound healing. However, the optimal effects of BMPs are modulated by a range of factors that need careful evaluation in clinical studies. These factors include the influence of root conditioning, occlusal loading, BMP dose, and the release characteristics of the carrier as well as the suitability of the model to evaluate the efficacy of BMPs. Each of these factors may affect the rate of BMP-induced osteogenesis and cementogenesis and subsequent periodontal ligament (PDL) formation during the early and late stages of periodontal wound healing. Although BMP-2 initiates stem cells along an osteogenic pathway, the dose may have to be of sufficient concentration to ensure other growth and differentiation factors do not redirect or retard the osteogenic potential of the cell. Understanding when to manipulate the cell's differentiation pathway with the application of single or multiple doses of BMPs at the appropriate concentration is required to optimize the effect of BMPs in periodontal wound healing. Therefore, different release profiles from the same carrier may be particularly important in tissues with mixed cell populations such as in the periodontium, where similar tissues like bone and cementum grow at different rates. Furthermore, treatment of intrabony defects with BMPs are likely to not only require appropriate temporal release of the BMP(s), but also a carrier that can serve as a template for new tissue formation providing space maintenance and supporting the mucoperiosteal flap. Many of these issues have not been adequately addressed from a periodontal standpoint; therefore the purpose of this review is to clarify our current understanding of the factors that are likely to modulate the effects of BMP-induced periodontal regeneration. Moreover, assessing the importance of these factors is essential prior to conducting expensive human clinical trials.