The overall goal of this U24 is to operationalize the Center for Dental, Oral and Craniofacial Tissue and Organ Regeneration (C-DOCTOR). Through an integrated series of collaborative planning activities funded during Stage I, eight renowned centers of translational research excellence - UCSF, USC, UCLA, UCB, UCD, UCSD, CoH, and Stanford - have partnered to form a public-private consortium focused on accelerating promising tissue engineering/regenerative medicine therapies for dental, oral, and craniofacial (DOC) tissue to human clinical trials. C-DOCTOR will recruit Interdisciplinary Translational Project (ITP) teams with promising DOC regeneration therapies and then provide scientific, technical, regulatory, financial, and managerial resources necessary to facilitate large animal model studies and promote a cost-effective transition to Stage III. C- DOCTOR will efficiently leverage an extensive array of existing resources that resonate with the Center mission. Three proposed Aims are to: 1) Recruit and select ITP teams that align with our clinical indication priorities; 2) Coordinate and customize our broad resource infrastructure along ITP team needs.; and 3) Cultivate, train, triage, and collaborate with ITP teams to assemble a balanced ITP portfolio ready for Stage III. To accomplish these aims, we will build on our preliminary needs assessment through a strong partnership with our diverse network of C-DOCTOR clinical advisors. We will then adapt best practices from a number of existing innovation programs across our multi-institutional network to select promising therapies with high potential for clinical adoption. C-DOCTOR Resource Directors will match selected ITP teams with domain and resource experts to refine their business case and address their technical needs through interactive collaboration, where continued funding and successful progression through Stage II will be dependent on meeting bi-annual milestones and specific go/no-go decision gates. In this manner, C-DOCTOR will efficiently and deliberately triage from a large number of promising ITPs into active partnership with only those that have maximum likelihood for successful transition through Stage III, which includes an FDA filing and commercial partnering that together support future Phase I clinical testing.

PROJECT NARRATIVE There is an implicit expectation that advancements in tissue regeneration research will lengthen and improve the quality of American lives. However, the clinical translation of new discoveries is often impeded by a number of trans-disciplinary obstacles related to intrinsic differences in authority structures, incentives, time perspectives, and language among basic scientists, clinicians, and industrial partners. The C-DOCTOR will overcome these obstacles by forming a novel and powerful resource to catalyze and accelerate clinical translation of promising dental, oral, and craniofacial (DOC) tissue engineering/regenerative medicine products. By doing so, the C-DOCTOR will provide a benefit not only within the US, but worldwide, through clinical and economic value creation.