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Towards a synthetic basement membrane for the corneal epithelium

角膜上皮合成基底膜的研究

基本信息

批准号：
7870311
负责人：
PAUL F. NEALEY
金额：
$ 35.96万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7870311
关键词：
Adhesions Adhesives Affect Apoptosis Architecture Area Arts Basement membrane Behavior Behavioral Assay Biocompatible Biocompatible Materials Biological Assay Biomimetic Materials Biomimetics Cell Proliferation Cell physiology Cell surface Cell-Matrix Junction Cells Cellular biology Chemistry Complex Cornea Development Devices Dimensions Engineering Epithelial Cells Epithelium Extracellular Matrix Proteins Future Gel Growth Factor Human Hydrogels In Vitro Integrins Laboratories Lead Ligands Maintenance Mediating Methodology Molds Molecular Biology Pattern Peptide Fragments Peptides Process Property Prosthesis Proteins Research Research Personnel Scanning Probe Microscopy Signal Pathway Signal Transduction Silicon Stem cells Stratified Epithelium Structure Surface Techniques Testing Tissue Engineering Tissues Work Writing adhesion receptor base cell behavior corneal epithelium density design functional group implantable device improved migration nano nanoscale novel programs protein aminoacid sequence receptor self-renewal submicron syndecan three dimensional structure

项目摘要

DESCRIPTION (provided by applicant): Basement membrane features that greatly influence cell function include compliance, specific proteins and functional groups, a reservoir of growth factor and other trophic agents, and a complex three-dimensional topography into which adherent cells extend processes, and formadhesion plaques. Thre three-dimensional submicron and nanoscale topography of the underlying substrate, and substrate compliance, independent of specific receptor-ligand interactions has been recently shown to influence fundamental cell behaviors. This proposal focuses on the interactions of corneal epithelial cells with biomimetic materials designed for integration into an implantable device. Our design parameters will be based on the premise that mimicking the structure, chemistry and compliance of the native basement membrane will be conducive to resurfacing and maintenance of a fully differentiated and functional epithelium by host cells. The overall purpose of this proposal is to determine the interaction of compliance, surface chemistry via adhesive peptide ligands, and topography mimicking features of the basement membrane underlying the corneal epithelium to determine design parameters for improved tissue architecture and function, and for integration into the design and fabrication of keratoprostheses. In this application, a multi-disciplinary approach is proposed to test 3 hyphothese using quantitative morphologic techniques, in vitro methodologies in cell biology, molecular biology and state-of-the-art nanoscale fabrication techniques. Hypothesis 1: Combined micro, submicron, and nanoscale topography and compliance will differentially affect cell attachment and spreading, proliferation, and migration. Hypothesis 2: Combining homogeneous and heterogeneous presentations of peptide sequences and topography will synergistically impact cell proliferation, adhesion and migration. Hypothesis 3: Combining biomimetic topography, compliance and surface chemistry will allow for the determination of materials parameters to enhance or retard cell behaviors within well-defined areas for integration into novel corneal equivalents.

描述（由申请人提供）：极大影响细胞功能的基底膜特征包括顺应性、特定蛋白质和官能团、生长因子和其他营养剂的储存库、以及贴壁细胞向其中延伸过程的复杂三维形貌，以及形成粘附斑。最近表明，独立于特定受体-配体相互作用的底层基质的三维亚微米和纳米级形貌以及基质顺应性会影响基本的细胞行为。该提案的重点是角膜上皮细胞与设计用于集成到可植入设备中的仿生材料的相互作用。我们的设计参数将基于这样的前提：模仿天然基底膜的结构、化学和顺应性将有利于宿主细胞重塑和维持完全分化和功能性的上皮。该提案的总体目的是确定顺应性、通过粘附肽配体的表面化学以及角膜上皮下基底膜的地形模拟特征之间的相互作用，以确定改善组织结构和功能的设计参数，并整合到角膜假体的设计和制造中。在此应用中，提出了一种多学科方法，使用定量形态学技术、细胞生物学体外方法、分子生物学和最先进的纳米级制造技术来测试 3 个假设。假设 1：微米、亚微米和纳米尺度的形貌和顺应性相结合将对细胞附着和扩散、增殖和迁移产生不同的影响。假设 2：结合肽序列和拓扑结构的同质和异质呈现将协同影响细胞增殖、粘附和迁移。假设 3：结合仿生地形、顺应性和表面化学将允许确定材料参数，以增强或延迟明确区域内的细胞行为，从而整合到新型角膜等效物中。