Regeneration of Clinically Relevant Orofacial Tissues in Pre-Clinical Models

描述（由申请人提供）：面部是人与人之间的区别。当面部因外伤、肿瘤切除、先天性异常或传染病而毁容时，患者会经历身体和心理创伤，因此对功能和美学重建有强烈的愿望。在过去的十年中，口腔面部结构的组织工程已经证明了单个组织碎片，如牙本质和骨，可以在体外或小动物模型中再生。然而，牙髓感染患者需要牙本质和牙髓的再生；面部深度缺损的患者不仅可以通过骨的再生来治愈，而且还可以通过附着在骨上的覆盖的血管化软组织来治愈。我们利用GO资助机制，将现有的临界质量和成熟的科学家和多学科外科医生聚集到一个联盟中，在临床前大型动物模型中再生牙髓-牙本质移植物和面部软组织-骨移植物。涉及牙髓-牙本质复合体的龋齿和创伤是牙科实践的支柱，目前仅在美国每年就有超过2400万例手术或约300亿美元。再生牙髓-牙本质移植物将改变这部分牙科实践。与此同时，生物再生面部软组织-骨移植将消除对自体组织移植的需求，并改变多个临床学科，包括口腔颌面外科、耳鼻喉/头颈外科、整形和重建外科。我们现有的干细胞生物学、材料科学、化学工程、机械工程、细胞和分子生物学、动物外科和临床知识等多学科专业知识，将继续推动临床相关的口面部组织再生进入I期人体临床试验。在之前与pi合作过的FDA顾问的协助下，我们将计划在目前的GO拨款中进行牙髓-牙本质移植和面部软组织-骨移植的首次人体临床试验。

DESCRIPTION (provided by applicant): The face distinguishes one human being from another. When the face is disfigured from injuries, tumor resection, congenital anomalies or infectious diseases, the patient experiences both physical and psychosocial trauma, and therefore has strong desire for both functional and esthetic reconstruction. In the past decade, tissue engineering of orofacial structures has provided the proof of concept that single tissue fragments, such as dentin and bone, can regenerate in vitro or in small animal models. However, patients with dental pulp infection need the regeneration of both dentin and dental pulp; patients with deep facial defects can only be healed not only by the regeneration of bone, but also the overlaying, vascularized soft tissue that is attached to bone. We take advantage of the GO grant mechanism to assemble an existing critical mass of and well established scientists and multi-disciplinary surgeons into a consortium to regenerate dental pulp-dentin grafts and facial soft tissue-bone grafts in a pre-clinical, large animal model. Dental caries and trauma involving the dental pulp-dentin complex is the pillar of dental practice, with a current volume over 24 million procedures or ~30 billion dollars annually in the United States alone. Regenerated pulp-dentin grafts will transform this segment of dental practice. In parallel, biologically regenerated facial soft tissue-bone grafts will eliminate the need for autologous tissue grafting, and transform multiple clinical disciplines including Oral & Maxillofacial Surgery, Otolaryngology/Head and Neck Surgery, and Plastic and Reconstructive Surgery. Our existing multi-disciplinary expertise in stem cell biology, materials science, chemical engineering, mechanical engineering, cell and molecular biology, animal surgery and clinical knowledge will continue to advance the regeneration of clinically relevant orofacial tissues into Phase I human clinical trials upon the completion of the present two-year GO grant. With assistance of a FDA consultant who has previously worked with the PIs, we will plan for first-in- human clinical trials on dental pulp-dentin grafts and facial soft tissue-bone grafts in the present GO grant. PUBLIC HEALTH RELEVANCE: We take advantage of the GO grant mechanism to assemble an existing critical mass of well established scientists and multi-disciplinary surgeons into a consortium to regenerate dental pulp-dentin grafts and facial soft tissue-bone grafts in a pre-clinical, large animal model. With assistance of a FDA consultant who has previously worked with the PIs, we will plan for first-in-human clinical trials on dental pulp-dentin grafts and facial soft tissue-bone grafts in the present GO grant.