Polymeric Matrices with Defined Cell Adhesion

描述(由申请人提供)： 涉及骨组织丢失的疾病和创伤是临床上最常见的牙科问题，我们建议开发用于骨组织工程的新型聚合物材料。我们假设，控制从聚合物提供给移植细胞的黏附配体的纳米级组织，以及这些配体对细胞介导的重排的敏感性，将调节细胞的基因表达。藻酸盐将被用作模型矩阵系统，以解决指导这一提议的假说。细胞几乎不与海藻酸盐黏附或相互作用，因此海藻酸盐提供了一个理想的“空白石板”，人们可以在上面以受控的方式赋予特定的细胞相互作用特性。与大多数模型系统相比，藻酸盐也是这项工作在体内应用的一种实用的生物材料。我们的具体目标是：(1)控制含有RGD的多肽在模型前成骨细胞系和人骨髓间充质干细胞中的纳米级递呈，并确定这如何调节局部黏附形成和细胞表型；(2)确定递呈凝胶的配体的硬度是否调节细胞重新排列黏附配体的能力；以及(3)确定这些变量是否允许人们调节体内新骨的形成。还将确定凝胶在降解之前呈现这种信息以调节细胞反应和骨形成所需的时间框架。这些目标的成功完成将在基础科学和应用科学方面产生重大影响，并最终可能导致再生骨缺损治疗方法的改进。建立纳米尺度的配体组织和基质力学性质调节细胞表型的机制，将为组织工程生物材料的设计和再生提供重要的新变量。在这项建议中开发的生物材料可能在各种临床环境中利用前体细胞再生骨组织的治疗中直接有用。

DESCRIPTION (provided by applicant): Diseases and trauma involving the loss of bony tissue are the most common clinical dental problems, and we propose to develop new polymeric materials for bone tissue engineering. We hypothesize that controlling the nanoscale organization of adhesive ligands presented to transplanted cells from the polymer, as well as the susceptibility of these ligands to cell-mediated rearrangement, will regulate the gene expression of the cells. Alginate will be used as a model matrix system to address the hypothesis guiding this proposal. Cells exhibit little to no adhesion or interaction with alginate, and thus alginate provides an ideal "blank slate" on which one can confer specific cellular interaction properties in a controlled manner. Alginate also, in contrast to most model systems, is a practical biomaterial for in vivo application of this work. We specifically aim to: (1) Control the nanoscale presentation of RGD-containing peptides to a model pre-osteoblast cell line and human mesenchymal stem cells, and determine how this regulates focal adhesion formation and cell phenotype, (2) determine if the stiffness of the ligand presenting gels regulates the cells ability to rearrange the adhesion ligands, and (3) determine if these variables allow one to regulate new bone formation in vivo. The time-frame required for the gel, before it degrades, to present this information in order to regulate the cell response and bone formation will also be determined. Successful completion of these aims will have significant impact in both basic and applied sciences, and may eventually lead to improved therapies for regenerating bone defects. Establishing the mechanism by which nanoscale ligand organization and matrix mechanical properties regulate cell phenotype will provide an important new variable for design of biomaterials in tissue engineering and regeneration. The biomaterials developed in this proposal may be directly useful in therapies utilizing precursor cells to regenerate bony tissues in a variety of clinical settings.