Biological mediators for periodontal regeneration.
A review of the literature on the use of growth-regulatory molecules in the oral cavity permits a model in which to consider approaches to oral tissue engineering. These concepts apply to periodontal regeneration and to regeneration of alveolar bone. In either case, the formation of tissues is complex but proceeds in a deliberate and orderly sequence. In these sequence of events resulting in either bone or cementum formation, periodontal ligament and bone can be stimulated at various points. Different signals can apparently be used to stimulate tissue formation including mitogenic signals and differentiation factors. Additionally, both hard and soft tissue stimulatory molecules appear to be permissive. Classic receptor-mediated peptides or extracellular matrix molecules for soft and hard tissues appear to allow stimulation of tissue formation cascades. Importantly, it also appears that the stimulatory event is transitory (that is, short-lived) and leads itself to a sequence of cellular events. These cellular events in turn stimulate a number of subsequent events (such as chemotaxis, proliferation, differentiation or angiogenesis), which lead to further progression of tissue formation. While a solid scientific rationale exists for the use of a variety of growth and attachment factors in regeneration of oral tissues, only a small number are being pursued clinically. Many therapeutic regimens have failed in preclinical testing or have resulted in limited regenerative capacity. The mitogenic polypeptides that stimulate soft tissue growth (such as platelet-derived growth factor) and both hard and soft tissue growth (such as transforming growth factor-beta) appear to have not led to successful enough outcomes to facilitate further work towards regulatory approval. The demonstrated ability of bone morphogenetic proteins to generate substantial quantities of bone suggest many applications in the oral cavity where this is the only tissue desired. Another therapeutic candidate is enamel matrix derivative, a set of matrix proteins. Enamel matrix derivative appears to stimulate first acellular cementum formation, which may allow for functional periodontal ligament formation. It will be of interest in the future to determine whether the protein matrix contains classic mitogenic or differentiation factors as well as the amelogenins. It is also evident that the bone morphogenetic proteins permit periodontal ligament formation. The conditions for stimulating predictable periodontal ligament tissues with bone morphogenetic proteins however are not known. It is clear that the bone morphogenetic proteins are excellent molecules for stimulating oral bone formation. The results of all these studies will determine the future therapeutic potential for these growth molecules such that they may be used to optimally stimulate and direct specific points along tissue formation cascades.