PROJECT SUMMARY Reconstruction of dental, oral, and craniofacial (DOC) tissues through tissue engineering and regenerative medicine (RM) is a major goal in dentistry. Despite the continuing success and commercial viability of RM approaches in selected areas of medicine, the application of RM concepts to DOC problems has not been well- implemented in clinical practice. To meet this need, the Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center (MPWRM RC) was established as an interdisciplinary partnership amongst the University of Michigan, the University of Pittsburgh, and the Wyss Institute, along with technology, clinical, regulatory, marketing, and commercial translation experts from private practice and industry. Through this collaborative effort, we will accelerate clinical adoption of promising technologies by providing the interdisciplinary expertise and resources to guide technologies towards FDA submissions. The vision of this RC is to safely and effectively regenerate, reconstruct, and restore functional DOC tissues. To achieve this vision and fulfill the goals of DOC Tissue Regeneration Consortium (DOCTRC), we will continue this cooperative agreement with NIDCR for Stage 3 to: 1) implement the RC structure and processes developed in Stage 2 to catalyze Interdisciplinary Translational Projects (ITPs) towards clinical adoption; 2) direct clinical translation and commercialization of ITP technologies; and 3) broaden DOCTRC impact and build sustainability. Each of these endeavors will be done in partnership with the Center for Dental Oral and Craniofacial Tissue and Organ Regeneration (C-DOCTOR), our companion RC. Under a cooperative agreement and partnership with NIDCR, we have forged strategic partnerships, built infrastructure, and integrated assessment and advising processes, to support 19 ITPs in Stage 2 of the DOCTRC initiative. All projects are beyond basic discovery with demonstrable preclinical proof-of-concept, rapidly maturing product development and commercial translation roadmaps, and strong clinical impact potential. From this set, 7 projects have been identified as candidates for the initial cohort of the Stage 3 ITP program with a subset of other projects entering Stage 3 as they mature. These projects represent a balanced portfolio with respect to clinical needs addressed and technology types, with corresponding product development pathways. Upon completion of Stage 3 of the DOCTRC initiative, we will have advanced a portfolio of technologies with a spectrum of associated risk to FDA submissions and commercialization, towards eventual clinical adoption. We will work to secure leveraged and follow-on funding for ITPs so they may progress to human clinical trials. Finally, the RC will share our approach with the RM communities beyond solely the projects in our portfolio. The impact of these efforts will be a catalysis of translation in the DOC arena never previously achieved in an NIH extramural program, resulting in the transformation of dental, oral, and craniofacial medicine.

PROJECT NARRATIVE Restoration of dental, oral, and craniofacial (DOC) tissues lost to disease, injury or congenital disorders is a major objective of oral reconstructive therapy. The goal of the Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is to translate tissue engineering and regenerative medicine innovations that address the ongoing clinical need to restore or create healthy, functional DOC tissues. The vision of this Resource Center is that the most promising technologies will be catalyzed by novel academic partnerships to safely and effectively regenerate, reconstruct and restore functional DOC tissues, leading to a transformation of patient care.