Nanotechnology Strategies for Growth of Bones and Teeth

描述(申请人提供)：本申请建议开发分子设计的多肽纳米结构，该结构可以在生理介质中触发祖细胞的分化和矿化，具有模仿牙釉质或骨基质的特征。这项拟议的研究是基于这样一个假设，即在纳米级设计的模板可以触发牙釉质和骨的再生，以呈现生物信号并诱导仿生矿化。利用体外实验，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齿培养和活体骨修复模型中的表现。这项研究将指导合成的、多功能的纳米结构模板的开发，这些模板可以用于硬组织(牙釉质或骨)的再生和修复，而不需要自体或自体组织移植。拟议计划的具体目标包括：开发将在生理流体中自组装并引发牙釉质或类骨基质仿生矿化的多肽两亲物，使用矿化、蛋白质和基因表达分析在体外与成骨细胞和成釉细胞测试这些纳米纤维系统，以及使用多肽两亲性纳米纤维的图案化基质或支架在体外和体内再生小鼠的牙齿和骨组织。拟议的研究计划是由四名研究人员共同努力的，他们专门从事自组装/材料化学、牙齿组织生物学和整形外科手术，他们的兴趣交叉于纳米科学和纳米技术在生物医学研究中的重点应用。

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.