The importance of drug delivery to optimize the effects of bone morphogenetic proteins during periodontal regeneration.

Bone morphogenetic proteins (BMPs) include a large number of proteins belonging to the TGF-beta superfamily which are characterized by their ability to induce bone and cartilage formation. Since the isolation and purification of BMPs by recombinant technology, the effects of single BMPs can now be evaluated in animal models. Subcutanous placement of a single recombinant BMP, such as recombinant human (rh) BMP-2, in a rat ectopic assay shows recruitment of undifferentiated mesenchymal cells, cartilage formation, followed by replacement with bone, formation of its own bone marrow and physiological bone remodelling. The therapeutic use of recombinant BMPs in the treatment of periodontal disease (destruction of the tooth ligaments, surrounding bone and tooth cementum, the latter of which anchors the ligaments to the tooth surface from the adjacent tooth socket) has attracted considerable interest due to their potent ability to stimulate intramembranous bone formation without an endochondral intermediate. Their predictability in stimulating new bone may provide an alternative that has greater osteogenic potential than autogenous bone, other growth factors and bone substitutes. The biological processes and the potential role of growth factors involved in promoting regeneration are complicated by the involvement of different cell types each with their different growth rates and responses to various stimuli. The major cell types involved in periodontal regeneration include osteoblasts, cementoblasts and fibroblasts. Here, the formation of the new mineralized layers on the tooth and bone surfaces by cementoblasts and osteoblasts respectively are a prerequisite before periodontal ligament formation and attachment by fibroblasts can occur. In this regard, BMPs are likely candidates to stimulate periodontal regeneration because of their ability not only to promote osteogenesis but also to stimulate cementogenesis (new cementum formation). However, understanding when to manipulate each of the various cells differentiation pathway with the application of single or multiple doses of BMPs at the appropriate concentration is dependent upon a suitable delivery system that can be modified in order to optimize its effect during periodontal wound healing. Furthermore, treatment of intrabony periodontal defects with BMPs are likely to not only require appropriate temporal release of the agent, but also adaptation of a carrier that is robust enough to maintain its integrity around the coronal aspect of the root in order to provide space maintenance and support the mucoperiosteal flap. This review evaluates the effects of different delivery systems upon BMP-induced periodontal regeneration.