Nanotechnology Strategies for Growth of Bones and Teeth

描述（由申请人提供）：本申请建议开发分子设计的肽纳米结构，可以触发祖细胞的分化和生理介质中的矿化，具有模拟牙釉质或骨基质的特征。提出的研究是基于这样的假设，即牙釉质和骨骼的再生可以通过纳米级设计的模板来触发，以呈现生物信号并诱导仿生矿化。通过体外实验，我们将研究这些仿生矿化模板如何影响成釉细胞和成骨细胞的基质合成，并测试它们在胚胎牙培养和体内骨修复模型中的表现。这项研究将指导合成、通用、纳米结构模板的发展，这些模板可用于硬组织（牙釉质或骨骼）的再生和修复，而无需自体或自体组织移植。拟议计划的具体目标包括：开发可在生理液体中自组装并触发牙釉质或骨样基质仿生矿化的肽亲两型纤维，利用矿化、蛋白质和基因表达试验，在体外用成骨祖细胞和成釉细胞测试这些纳米纤维系统，并在小鼠模型中使用肽亲两型纳米纤维的图案底物或支架进行牙和骨组织的体外和体内再生。拟建的研究项目是由四名研究人员合作完成的，他们专攻自组装/材料化学、牙科组织生物学和骨科外科，他们的兴趣集中在纳米科学和纳米技术在生物医学研究中的应用。

DESCRIPTION (provided by applicant): This application proposes to develop molecularly designed peptide nanostructures that can trigger differentiation of progenitor cells and mineralization in physiological media with features that mimic enamel or bone matrices. The proposed research is based on the hypothesis that regeneration of enamel and bone can be triggered by templates designed at the nanoscale to present biological signals and induce biomimetic mineralization. Using in vitro assays, we will investigate how these biomimetic mineralization templates affect matrix synthesis by ameloblasts and osteoprogenitor cells, and also test their performance in embryonic tooth culture and in vivo bone repair models. This research will guide the development of synthetic, versatile, nanostructured templates that can be used for hard tissue (enamel or bone) regeneration and repair without the need for autologous or autogenic tissue transplantation. The proposed program's specific aims include: development of peptide amphiphiles that will self-assemble in physiological fluids and trigger biomimetic mineralization of enamel- or bone-like matrices, testing of these nanofiber systems in vitro with osteoprogenitor and ameloblast cells using mineralization, protein and gene expression assays, and using patterned substrates or scaffolds of peptide amphiphile nanofibers for in vitro and in vivo regeneration of dental and bone tissues in murine models. The proposed research program is a collaborative effort of four investigators specializing in self-assembly/materials chemistry, dental tissue biology and orthopedic surgery, whose interests intersect on the focused application of nanoscience and nanotechnology to biomedical research.