Tooth loss continues to plague many Americans, and is complicated by bone resorption in the jaw. Current therapies for tooth replacement include synthetic dental implants, but these devices do not maintain the health of surrounding tissues and require sufficient amounts of alveolar bone to secure the implant. The ability to replace lost or diseased dentition and alveolar bone with healthy, biological teeth would revolutionize the practice of dentistry and oral surgery. Our long-term goal is to bioengineer biological tooth replacements containing enamel, dentin and pulp, and roots anchored to the underlying alveolar bone via periodontal ligament. Our current bioengineered tooth Crowns exhibit variable amounts of enamel and Jentin, and lack mature root structures. We expect that bioengineered tooth root formation will be enhanced by growth in close proximity to developing bone. This hypothesis will be tested by growing composite bioengineered tooth/bone constructs in the jaws of Yucatan mini-pigs. Excised implants will be analyzed for the presence of tooth crowns, mature tooth root structures, and alveolar bone. We will empirically determine the specific ratio of dental epithelial to mesenchymal cells seeded onto scaffolds required to bioengineer dentin and enamel of appropriate relative thickness. Thus, our Specific Aims are to: 1) demonstrate the coordinated formation of tooth crowns, roots and bone by bioengineering tooth and alveolar bone segments grown in the jaws of pigs, and 2) to bioengineer tooth crowns containing the relative amounts of enamel and dentin present in naturally formed teeth. We anticipate that the successful bioengineering of mature teeth anchored to alveolar bone via roots and periodontal ligament will provide an alternative therapeutic treatment for dental and oral cancer patients, and for individuals suffering from a variety of craniofacial defects.