Bioengineered Composite Alveolar Bone-Tooth Constructs for Tooth Regeneration

用于牙齿再生的生物工程复合牙槽骨牙齿结构

• 批准号: 9444207
• 负责人: PAMELA C YELICK
• 金额: $ 77.86万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9444207
• 关键词: Accidents; Address; Adult; Affect; Age; Alveolar; Alveolar Bone Loss; Animal Model; Athletic Injuries; Autologous; Biomedical Engineering; Biomimetics; Blood; Bone Regeneration; Bone Resorption; Bone Tissue; Cells; Child; Clinical Trials; Complex; Congenital Abnormality; Craniofacial Abnormalities; Data; Defect; Dental; Dental Implants; Dentistry; Dentition; Development; Dimensions; Disease; Excision; Exhibits; Extracellular Matrix; Family suidae; Gelatin; Genetic; Goals; Growth Factor; Harvest; Health; Health Priorities; Human; Hydrogels; Immune system; Implant; Individual; Injury; Interdisciplinary Study; Jaw; Knowledge; Live Birth; Malignant Neoplasms; Mandible; Maxilla; Methacrylates; Methods; Military Personnel; Minerals; Mission; Modeling; Morbidity - disease rate; Natural regeneration; Nerve; Operative Surgical Procedures; Oryctolagus cuniculus; Persons; Population; Property; Public Health; Publishing; Quality of life; Regenerative Medicine; Replacement Therapy; Reporting; Research; Signal Pathway; Silk; Site; Source; Techniques; Technology; Time; Tissue Engineering; Tissues; Tooth Germ; Tooth Loss; Tooth Tissue; Tooth regeneration; Tooth structure; United States; United States National Institutes of Health; aging population; alveolar bone; base; bioprinting; bone; cleft lip and palate; clinically relevant; craniofacial; craniofacial complex; craniofacial development; craniofacial repair; design; healing; improved; innovation; malignant mouth neoplasm; novel; novel strategies; oral surgery specialty; regenerative; repaired; scaffold; skeletal; tissue support frame

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.

项目总结/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， 包括血液、脉管系统和神经在内的组织数量惊人地多，而且还在不断增加， 与免疫系统和多种生长因子信号传导途径。虽然信号的知识 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，详细介绍了 知识和了解如何再生人体矿化组织在功能和及时 方式仍然难以捉摸-特别是关于颅面复合体和牙齿。 在这里，我们提出了新的策略，以有效和协调再生牙槽骨和牙齿组织， 使用三维组织工程策略。拟议研究的目标，建立在 我们先前发表的报告，是表征两个潜在的模型，仿生三维肺泡 骨-牙构建体：1）天然脱细胞牙芽细胞外基质支架;和2）明胶 甲基丙烯酸酯（GelMA）水凝胶支架。 我们在再生牙科，矿化组织发育和疾病领域的专业知识， 强大的初步数据，以及发育生物学家，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。我们预计，在完成拟议研究后， 显著提高了对修复颅面缺损新方法的认识和理解， 各种侮辱。 拟议研究的重要性和与公共卫生的相关性包括骨骼和 仅在美国，每700名活产婴儿中就有1名发生颅面缺陷， 2014年进行了100万例颌面外科手术，包括口腔癌切除术。此外，受伤 由于事故和运动损伤，包括牙齿在内的颅面复合体越来越常见， 特别是在战场上，它们占受伤人数的20%。因此，拟议的研究将使 为改善平民和军人的生活质量作出了重大贡献。