Periodontitis, the inflammation of the periodontium, affects ~30-50% of the U.S. population. Untreated periodontitis leads to progressive loss of the periodontal ligament, cementum and alveolar bone, ultimately resulting in tooth loss. Bone grafting procedures are performed for patients with severe bone loss. Autologous bone is harvested from retro-molar area, the chin, the palate and even iliac crest. Allogeneic and xenogenic bone grafts derive from cadaver or non-human species, typically in the form of bone cubes or particulates that require extensive processing and hence are costly. Our preliminary data show that several known or novel molecules had significantly greater capacity for osteogenesis and cementogenesis in vivo than current commercial products by activating canonic ?-catenin signaling in stem/progenitor cells. We have performed in- depth molecular signaling studies to ascertain osteogenic and cementogenic properties of two novel molecules. As a translational step, we purified recombinant full-length proteins from E. coli., an industry standard procedure for recombinant protein production. The overall objective of this SBIR Phase I application is to develop several periodontal regeneration prototypes with novel molecules and benchmark them against a market leader of biologically derived product. We anticipate, from our in-depth molecular signaling and in vivo data that the two novel molecules will outperform the existing commercial product by a substantial margin.