Polymeric Matrices with Defined Cell Adhesion

具有明确细胞粘附力的聚合物基质

• 批准号: 7751849
• 负责人: David J Mooney
• 金额: $ 37.05万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7751849
• 关键词: 3-Dimensional; Acrylamides; Actomyosin; Address; Adhesions; Adhesives; Affect; Affinity; Alginates; Area; Arginine; Aspartic Acid; Atomic Force Microscopy; Award; Binding; Biocompatible Materials; Biological Assay; Biotin; Bone Regeneration; Calcium; Calibration; Cartilage; Cell Adhesion; Cell Communication; Cell Count; Cell Culture Techniques; Cell Cycle; Cell Density; Cell Proliferation; Cell Transplants; Cell membrane; Cells; Chemicals; Cleaved cell; Collagen; Color; Commit; Confocal Microscopy; Coupled; Cues; Cyclic Peptides; DNA; DNA Sequence Rearrangement; Data; Dental; Dependence; Dependency; Development; Dimensions; Elasticity; Encapsulated; Energy Transfer; Extracellular Matrix; Fibronectins; Figs - dietary; Fluorescein; Fluoresceins; Fluorescence; Fluorescence Resonance Energy Transfer; Gel; Gene Expression; Gene Transfer; Genetic Materials; Glycine; Gold; Graph; Growth Factor; Height; Hydrogels; Image; In Situ; In Vitro; Incubated; Integrins; Label; Laminin; Lead; Left; Life; Ligand Binding; Ligands; Link; Lipids; Luciferases; Maps; Measurement; Measures; Mechanics; Mediating; Membrane; Mesenchymal Stem Cells; Mica; Microfilaments; Molecular Weight; Monitor; Myoblasts; Nanostructures; Osteoblasts; Osteocalcin; Osteogenesis; Panthera leo; Penetration; Peptides; Phenotype; Polymers; Population; Property; Publications; RGD (sequence); RGD Receptor; Radial; Receptor Cell; Research; Role; Scanning Probe Microscopes; Screening procedure; Series; Site; Solutions; Specificity; Spectrum Analysis; Staging; Streptavidin; Structure; Suggestion; Surface; Synthetic Peptide Libraries; System; Techniques; Testing; Thymidine; Time; Tissues; Traction; adhesion receptor; analog; base; bone; cell type; cellular imaging; craniofacial; crosslink; density; design; fluorophore; gene therapy; in vivo; inhibitor/antagonist; matrigel; nanoparticle; nanoscale; non-viral gene delivery; non-viral gene therapy; novel; novel strategies; osteoblast differentiation; osteoprogenitor cell; physical property; plasmid DNA; receptor; research study; response; single cell analysis; spectroscopic imaging; stem cell differentiation; success; tetramethylrhodamine; tool; uptake; vector

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.

该项目的长期目标是开发促进新骨形成的材料系统 重建牙科和颅面应用。指导我们研究的总体假设是 可以基于对细胞受体材料的基本和定量理解来设计材料系统 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 这些细胞形成组织。这个假设代表了我们当前努力开发的延续 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（配体的类型、密度、间距和呈现底物的机械性能） 骨祖细胞分化和骨形成。扩展中要检验的具体假设 该优异奖是藻酸盐凝胶的机械性能和细胞粘附配体呈现 可以进行调整以特异性促进间充质干细胞 (MSC) 粘附、增殖和 分化，并增强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的技术来进行单细胞分析 受体-配体结合动力学（kon、koff、KD）以确定配体如何呈递（密度、 间距、凝胶机械性能）调节键的形成，(2) 以此分析 kon、koff 和 KD 使用源自天然细胞外基质分子的合成肽库的技术（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递的能力 从大规模筛选中选出，以增强移植细胞群的骨再生， 宿主细胞群。这些研究的成功将带来可以显着增强骨骼的生物材料 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。