Regeneration of Clinically Relevant Orofacial Tissues in Pre-Clinical Models

描述(由申请人提供)：面孔是人与人之间的区别。当面部因损伤、肿瘤切除、先天畸形或传染病而毁容时，患者既经历了身体上的创伤，也经历了心理上的创伤，因此对功能和审美重建都有强烈的渴望。在过去的十年中，口腔面部结构的组织工程学已经提供了概念证明，即单个组织碎片，如牙本质和骨，可以在体外或在小动物模型中再生。然而，牙髓感染患者需要牙本质和牙髓的再生；面部深部缺损的患者不仅可以通过骨的再生，还可以通过附着在骨上的覆盖的、有血管的软组织来愈合。我们利用围棋赠款机制，将现有的关键数量和知名的科学家和多学科外科医生组成一个联盟，在临床前的大型动物模型中再生牙髓-牙本质移植和面部软组织-骨移植。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。再生的牙髓-牙本质移植将改变这一领域的牙科实践。同时，生物再生的面部软组织-骨移植将不再需要自体组织移植，并改变包括口腔颌面外科、耳鼻喉科/头颈外科以及整形和重建外科在内的多个临床学科。我们现有的在干细胞生物学、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方面的多学科专业知识，将在目前为期两年的GO拨款结束后，继续推动具有临床意义的口腔面部组织再生进入第一阶段人类临床试验。在FDA顾问的协助下，我们将在今年的GO拨款中，计划对牙髓-牙本质移植和面部软组织-骨移植进行首例人类临床试验。 公共卫生相关性：我们利用GO赠款机制，将现有的关键数量的知名科学家和多学科外科医生聚集成一个联合体，在临床前的大型动物模型中再生牙髓-牙本质移植和面部软组织-骨移植。在FDA顾问的协助下，我们将在今年的GO拨款中，计划对牙髓-牙本质移植和面部软组织-骨移植进行首例人类临床试验。

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.