Bioengineered Composite Alveolar Bone-Tooth Constructs for Tooth Regeneration

项目摘要/摘要 颅面颌骨和牙齿的协调发展是一个复杂的相互作用的结果 令人惊讶的是，数量越来越多的组织--包括血液和血管系统，以及神经--结合在一起 与免疫系统和多种生长因子信号通路有关。虽然信令方面的知识 导致人类矿化组织发育的途径在过去几十年中得到了改善，详细说明 了解和理解如何及时、有效地再生人体矿化组织 特别是在头面部复合体和牙齿方面，这种方式仍然难以捉摸。 在这里，我们提出了有效和协调地再生牙槽颌骨和牙齿组织的新策略， 使用三维组织工程策略。拟议研究的目标，其基础是 我们先前发表的报告描述了两种可能的仿生三维肺泡模型。 骨牙支架：1)天然脱细胞牙蕾细胞外基质支架；2)明胶 甲基丙烯酸酯(GelMA)水凝胶支架。 我们在再生牙科、矿化组织开发和疾病领域发表的专业知识， 强大的初步数据，发育生物学家、临床医生和生物工程师团队支持我们的能力 以实现所提出的目标。我们预期拟议研究的完成将导致 显著提高了对新方法的认识和理解，以修复由 各种各样的侮辱。 拟议研究的意义和与公共卫生的相关性包括以下事实：骨骼和 仅在美国，每700名活产儿中就有1人出现头面部缺陷，超过四分之一 在2014年进行的100万例颌面部手术中，包括口腔癌切除。此外，受伤 由于事故和运动损伤，包括牙齿在内的头面部复合体越来越常见，以及 特别是在战场上，他们占受伤人数的20%。因此，拟议的研究将使 对改善平民和军人的生活质量作出了重大贡献。

Project Summary/Abstract The coordinated development of craniofacial jaw bones and teeth are the result of a complex interplay between a surprisingly large and growing number of tissues - including blood and vasculature, and nerves – combined with the immune system, and a multitude of growth factor signaling pathways. Although knowledge of signaling pathways resulting in human mineralized tissue development has improved over the past few decades, detailed knowledge and understanding of how to regenerate human mineralized tissues in a functional and timely manner remains elusive – particularly with respect to the craniofacial complex and teeth. Here we propose novel strategies to effectively and coordinately regenerate alveolar jaw bone and tooth tissues, using three dimensional tissue engineering strategies. The objectives of the proposed studies, which build on our prior published reports, are to characterize two potential models for biomimetic three dimensional alveolar bone-tooth constructs: 1) natural decellularized tooth bud extracellular matrix scaffolds; and 2) Gelatin Methacrylate (GelMA) hydrogel scaffolds. Our published expertise in in the field of regenerative dentistry, mineralized tissue development and disease, strong preliminary data, and team of developmental biologists, clinicians and bioengineers supports our ability to accomplish the proposed Aims. We anticipate that the completion of the proposed studies will result in significantly improved knowledge and understanding of new methods to repair craniofacial defects caused by a variety of insults. The significance of the proposed studies and relevance to public health includes the facts that skeletal and craniofacial defects occur in as many as 1 in 700 live births in the United States alone, and that over a quarter of a million Maxillofacial surgeries were performed in 2014, including oral cancer resections. In addition, injuries to the craniofacial complex that include teeth are increasingly common due to accidents and sports injuries, and particularly in the battlefield where they represent up to 20% of injuries. As such, the proposed studies will make a significant contribution towards improved quality of life of both civilian and military populations.