Polymeric Matrices with Defined Cell Adhesion

该项目的长期目标是开发促进新骨形成的材料系统， 重建牙齿和颅面应用。指导我们研究的总体假设是 基于对细胞受体材料的基本和定量的理解， 配体结合，为混合物中存在的特定细胞类型提供选择性优势，并引导 这些细胞的组织形成。这一假设代表了我们目前努力的延续， 通过理解和操纵细胞粘附肽的作用来促进骨再生的材料 呈现（类型、密度、配体间距和呈现基底的机械性质） 骨祖细胞分化和骨形成。在扩展中要检验的具体假设 这个MERIT奖是藻酸盐凝胶的机械性能和细胞粘附配体呈现， 可以被调节以特异性地促进间充质干细胞（MSC）的粘附、增殖和 分化，并增强来自移植细胞群或诱导宿主的体内骨再生 细胞具体目标包括：（1）开发基于FRET的技术，以进行单细胞分析， 受体-配体结合动力学（kon、koff、KD）以确定配体如何呈现（密度， 间距，凝胶机械性能）调节键的形成，（2）分析kon，koff和KD与此 使用源自天然细胞外基质分子的合成肽文库的技术（例如， 纤连蛋白、胶原蛋白、层粘连蛋白），以鉴定对MSC粘附具有高特异性的材料， 可能不同的分化阶段，以及（3）测试特定配体和配体呈现的能力 从大规模筛选中选择，以增强来自移植细胞群的骨再生， 宿主细胞群体。这些研究的成功将导致生物材料可以显着增强骨骼 通过特异性促进少量细胞的粘附、增殖和分化来再生 骨祖细胞通常存在于体外或体内的细胞群中。

The long-term objective of this project is to develop material systems that promote new bone formation for reconstructive dental and craniofacial applications. The overall hypothesis guiding our research is that material systems may be designed, based on a fundamental and quantitative understanding of cell receptormaterial ligand binding, to provide a selective advantage to specific cell types present in a mixture, and guide tissue formation from these cells. This hypothesis represents a continuation of our current effort to develop materials to promote bone regeneration by understanding and manipulating the role of cell adhesion peptide presentation (type, density, spacing of ligand, and mechanical properties of presenting substrate) in osteoprogenitor differentiation and bone formation. The specific hypothesis to be tested in the extension of this MERIT award is that the mechanical properties and cell adhesion ligand presentation of alginate gels may be tuned to specifically promote mesenchymal stem cell (MSC) adhesion, proliferation and differentiation, and enhance bone regeneration in vivo from transplanted cell populations or induced host cells. The specific aims will include: (1) Develop a FRET-based technique to perform single cell analysis of receptor-ligand binding dynamics (kon, koff, KD) in order to determine how ligand presentation (density, spacing, gel mechanical properties) regulate bond formation, (2) Analyze kon, koff, and KD with this technique using libraries of synthetic peptides derived from natural extracellular matrix molecules (e.g., fibronectin, collagen, laminin) in order to identify materials with high specificity for MSC adhesion and possibly distinct stages of differentiation, and (3) Test the ability of specific ligands and ligand presentations chosen from the large-scale screening to enhance bone regeneration from transplanted cell populations and host cell populations. Success in these studies will lead to biomaterials that can dramatically enhance bone regeneration by specifically promoting the adhesion, proliferation and differentiation of the small numbers of osteoprogenitors typically present in cell populations, either in vitro or in vivo.