DESCRIPTION (provided by applicant): The goal of the proposed planning grant is to design the foundations for a multidisciplinary Tissue Regeneration Consortium that will conduct pre-clinical studies leading to the submission of an IND application to the U.S. FDA for craniofacial critical defect regeneration. It is estimated that 42,000 Americans and approximately 640,000 people worldwide are diagnosed with oral cancer each year, which is the main cause of maxillectomy or mandibulectomy. In these circumstances, grafts are typically used to repair the defect. Approximately 1.6 million bone grafts are used each year to regenerate bone lost due to trauma or disease, 6% of which are craniomaxillofacial in nature. Today, the `gold standard' of bone grafts is an autograft. Unfortunately, the harvest of an autograft is not always possible and might lead to co-site morbidity and excessive pain. Another option is the allograft, which is readily available but has limited bone formation capability. Therefore, there is a clear clinical need to develop new bone grafts that are both readily available and can efficiently replace the tissue that was lost. To address this major clinical problem, the members of the proposed consortium have established an array of adult stem cells and biomaterials that have been extensively tested in animal models, and some have also been evaluated in clinical trials. Here we propose to build on these therapeutic candidates in order to develop stem cell-biomaterial composites that would receive FDA approval for clinical evaluation. Our primary target product is a tissue-engineered periosteum composed of a stem cell sheet and custom 3D-printed scaffolds for craniofacial segmental defect repair. Our specific goals for the planning period are: 1. Identify the exact product profile. 2. Establish a preclinical development plan. 3. Define a CMC and Manufacturing plan. 4. Establish a regulatory plan. 5. Define a clinical development plan.

PUBLIC HEALTH RELEVANCE Our long-term goal is to establish a resource center for craniofacial tissue engineering that will support pre-clinical studies leading to the submission of a new IND to the FDA. Towards this goal we have assembled a team of experts in the fields of: stem cells, biomaterials, FDA regulations, good manufacturing practice and craniofacial surgery. During the planning grant period we aim to establish the organization of the Resource Center, required SOPs, scientific advisory board and clinical board, animal models, outcome measures, and product development plans.