The Tooth

The tooth itself is a cranio-facial structure that is the focus of intensive tissue engineering studies. The outer enamel layer is almost 95 percent mineral, the hardest structure in the body. During its formative stages enamel consists of a protein matrix that forms the framework for mineral deposition. The matrix proteins have been identified and cloned and now scientists hope to use this knowledge to replicate the natural enamel-forming process. Amelogenin, produced by specialized cells called ameloblasts, is the major enamel protein, constituting about 90 percent of the matrix material. Amelogenin is believed to play a role in developing enamel by stabilizing newly formed enamel crystals and in uencing their subsequent growth. In addition to amelogenin, there are other proteins such as tuftelin and ameloblastin that play an undetermined role in enamel formation. There is compelling evidence that enamel formation begins at the outer edge of the dentinal layer, at the dentino-enamel junction. Crystallite ribbons rise up from the dentin and are separated by globules, or nanospheres of amelogenin. The nanospheres appear to spiral upward around the growing crystallites, eventually degrading and ultimately disappearing as the crystallite ribbons coalesce into solid enamel. The secret to duplicating this process may lie in isolating the progenitor cells that control the mineralization process and putting them in a three-dimensional environment seeded with the necessary signaling molecules. NIDCR grantees are attempting to reproduce the enamel-forming process in the laboratory and to create a novel bioceramic that will make current restorative materials obsolete.

Amelogenin is also involved in the formation of the tooth's cementum layer, which occurs along the root surface. Cementum is not as hard as enamel and generally contains less mineral and more collagen. It is in the area of cementum regeneration where the greatest strides in tooth tissue engineering have been made. An amelogenin-based product, called Emdogain, was developed in Sweden and currently is in use in the U.S., Europe and Canada. Emdogain is based o­n a formula using a swine amelogenin as the active component, mixed with polypropylene glycol alginate (PGA) carrier a viscous material used by the food industry as a thickener. In human trials, Emdogain stimulated the formation not o­nly of new cementum, but also new jawbone and the intervening periodontal ligament. It is thought that the amelogenin in Emdogain may be the stimulus that prompts stem cells in the periodontal ligament to divide and differentiate, and produce the additional proteins required for regeneration of the periodontium.