Biomimetic Properties of Cementum and its Interfaces

描述（由申请人提供）：NIH独立之路奖K99/R00申请的总体目的是为指导阶段提供一年的支持，该阶段对于完成四个假设的关键测试至关重要，随后将稿件提交给相关期刊。接下来的3年独立阶段是建立我的研究计划和实现我作为初级教师的目标所必需的。这将使我成为一名独立的生物材料整合和表征研究者，同时考虑到人类和类似的动物组织，随后构建具有良好优化的生物工程界面的组织。这个奖项将使我能够研究这个提案中所定义的具体目标，并扩展我在构建下一代组织再生材料方面的知识。这些努力的重点是基于一个普遍的假设，即牙齿的功能生物力学来源于其不同成分在几个层次（宏观、微观和纳米尺度）上的结构和化学相互作用，并且这些产生的特性取决于位置、年龄和性别。包括牙周韧带（PDL）、牙骨质和骨骼在内的组织的破坏会导致牙周炎导致的牙齿脱落。主要挑战包括1)。了解与疾病进展相关的组织降解；2)。将口腔组织结合在一起的界面再生。为了解决第一个挑战，将开发牙周炎的动物模型，并通过研究组织的结构，化学成分和力学性能来确定组织的顺序变性。对于第二个挑战，组织工程（TE）可以用来制造新的支架。然而，目前TE手术的一个主要限制是对支架生物力学的了解有限。一个有效的支架除了提供一个有利于期望细胞行为的环境外，还应该承受功能负荷。为了应对这些挑战，必须确定组织及其界面的固有特征。然后，它们可以用TE来模拟，以创建合适的支架。因此，将以下具体目标定义为：1)。研究初级和次级牙骨质的结构、化学成分和力学性能；研究牙骨质的结构、化学成分、力学性能及其与牙根的界面，3)。研究使用前牙和后牙功能载荷的应变场与年龄的关系，4)。对健康人类和大鼠的牙槽骨、牙骨质、牙骨质、牙根及其生物材料界面的结构、化学成分和力学性能进行比较研究。这些信息将用于确定大鼠牙周组织及其生物材料界面在疾病进展过程中结构、化学成分和机械性能的时间变化。

DESCRIPTION (provided by applicant): The overall purpose of the NIH Pathway to Independence Award K99/R00 application is to provide a year of support for the mentored phase that is crucial in completing the critical testing of four hypotheses, followed by manuscript submission to relevant journals. The subsequent 3 year independent phase is necessary to establish my research program and reaching my goals as a junior faculty member. It would enable me to establish myself as an independent investigator in biomaterials integration and characterization taking into account both human and comparable animal tissues, subsequently building tissues with well optimized bioengineered interfaces. This award will enable me to study the proposed specific aims defined in this proposal and expand my knowledge on building the next generation materials for tissue regeneration. The thrust of these efforts is based on a general hypothesis that the functional biomechanics of a tooth are derived from structural and chemical interactions of its different components at several hierarchical levels (macro-, micro- and nano-scales), and that these yield properties that depend on location, age, and gender. Destruction of tissues including the periodontal ligament (PDL), cementum, and bone can cause loss of teeth due to periodontitis. Key challenges include 1). Understanding degradation of the tissues associated with disease progression, and 2). Regeneration of the interfaces that bind the oral tissues together. To address the first challenge, an animal model for periodontitis will be developed and the sequential degeneration of tissues determined by studying their structure, chemical composition and mechanical properties. For the second challenge, tissue engineering (TE) can be used to create novel scaffolds. However, a major limitation of current TE procedures is limited knowledge of scaffold biomechanics. An efficient scaffold should sustain functional loads in addition to providing an environment conducive to desired cell behavior. To address these challenges, the inherent characteristics of the tissues and their interfaces must be determined. Then, they can be mimicked using TE to create appropriate scaffolds. Hence the following specific aims are defined to: 1). Investigate structure, chemical composition, mechanical properties of primary and secondary cementums, 2). Investigate structure, chemical composition, mechanical properties of cementum and its interface with root dentin, 3). Investigate strain fields using functional loads on anterior and posterior teeth as a function of age, 4). Perform a comparison studies between structure, chemical composition and mechanical properties of healthy human and rat alveolar bone, PDL, cementum, root dentin and their biomaterial interfaces. This information will be used to determine chronological changes in structure, chemical composition and mechanical properties in the rat periodontal tissues and their biomaterial interfaces during disease progression.