Regeneration of Clinically Relevant Orofacial Tissues in Pre-Clinical Models

描述（由申请人提供）：面部将一个人与另一个人区分开来。当面部因外伤、肿瘤切除、先天畸形或感染性疾病而毁容时，患者会经历生理和心理创伤，因此对功能和美学重建有强烈的愿望。在过去的十年中，口腔颌面结构的组织工程已经提供了概念证明，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，牙髓感染的患者需要牙本质和牙髓的再生;面部深层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、血管化的软组织来愈合。我们利用GO赠款机制，将现有的关键质量和成熟的科学家和多学科外科医生组成一个联盟，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，仅在美国，目前每年的手术量超过2400万次或约300亿美元。再生牙髓牙本质移植将改变这部分牙科实践。同时，生物再生的面部软组织-骨移植物将消除对自体组织移植的需要，并改变多个临床学科，包括口腔颌面外科，耳鼻咽喉/头颈外科以及整形和重建外科。我们现有的多学科专业知识，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将继续推进临床相关的口腔颌面组织再生到第一阶段人体临床试验完成后，目前为期两年的GO赠款。在一位曾与PI合作过的FDA顾问的帮助下，我们将计划在目前的GO赠款中进行牙髓牙本质移植物和面部软组织骨移植物的首次人体临床试验。 公共卫生相关性：我们利用GO赠款机制，将现有的大量知名科学家和多学科外科医生组成一个联盟，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。在一位曾与PI合作过的FDA顾问的帮助下，我们将计划在目前的GO赠款中进行牙髓牙本质移植物和面部软组织骨移植物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.