Combinatorial Metal Oxide Substrates to Enhance Osteogenic Stem Cell Functions

组合金属氧化物基质增强成骨干细胞功能

基本信息

批准号：
8018112
负责人：
JAIME E RAMIREZ-VICK
金额：
$ 10.43万
依托单位：
UNIVERSITY OF PUERTO RICO MAYAGUEZ
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8018112
关键词：
Adhesions Adhesives Adsorption Affect Alloys Applications Grants Area Atomic Force Microscopy Binding Biocompatible Materials Biological Assay Bone Tissue Cell Adhesion Cell Communication Cell Culture Techniques Cell physiology Cell surface Cell-Cell Adhesion Cells Chemicals Chemistry Clinic Clinical Collagen Type I Complex Cultured Cells Data Dental Deposition Detection Development Diffusion Distant Drug Formulations Economics Electron Probe Microanalysis Engineering Environment Exhibits Extracellular Matrix Fibronectins Film Fluorescence Microscopy Foundations Functional disorder Gene Expression Genes Goals Heparin Binding Hour Immunofluorescence Microscopy Implant In Vitro Institution Interleukin-11 International Investigation Knowledge Laminin Laser Scanning Confocal Microscopy Libraries Life Liquid substance Location Marketing Measurement Mechanics Membrane Proteins Mesenchymal Stem Cells Messenger RNA Metals Microscopy Modeling Molecular Conformation Morphology Orthopedics Osseointegration Osteoblasts Osteocalcin Osteogenesis Outcome Oxides Peer Review Physiology Plasma Population Procedures Process Prosthesis Protein Conformation Proteins Publications RGD (sequence)Research Research Activity Roentgen Rays Scanning Electron Microscopy Science Scientist Screening procedure Serum Spectrometry Spectroscopy, Fourier Transform Infrared Spectrum Analysis Staging Stem cells Stimulus Surface Surface Properties TNF gene TNFSF11 gene Techniques Technology Testing Therapeutic Thick Tissue Engineering Tissue Model Tissues Titania Titanium Training Transcript Translating Vitronectin base bone healing cell behavior cell motility cell type cold temperature combinatorial graduate student hip replacement arthroplasty human tissue implant material improved in vivo interest metal oxide migration nano nanostructured novel osteogenic osteopontin protein distribution public health relevance scaffold stem cell differentiation symposium vapor

项目摘要

DESCRIPTION (provided by applicant): The overall objective of this project is to develop a foundation for a biomaterial screening strategy based on combinatorial materials science. This approach will provide substrates with a range of subtle changes in surface properties and composition. The efficacy of these novel material formulations will be determined in vitro using cell-culture models and by conducting a systematic investigation of the effects of the elemental composition of the biomaterial surface chemistry and topography on mesenchymal stem cell (MSC) differentiation and functions pertinent to new bone formation. The central hypothesis is that the metal oxide surface of the material substrate modulates the type, distribution and conformation of adsorbed proteins, these proteins direct and modulate subsequent cell interaction and function pertinent to new tissue formation. Specific Aim 1: Develop metal oxide substrates based on titanium that contain gradients of three other metals used as implant materials. It is hypothesized that, annealing by plasma-enhanced chemical vapor deposition, will generate concentration gradients using thin films of variable thickness sputtered onto Ti substrates. Specific Aim 2: Determine the type, distribution and conformation of select serum and/or ECM adhesive proteins such as collagen type I, fibronectin, laminin, and vitronectin, adsorbed onto the novel material substrates prepared by the research activities pertinent to Specific Aim 1. Specific Aim 3: Assess the osteogenic differentiation of MSCs onto the nanostructured substrates. It is hypothesized that following adhesion, MSCs migration will be affected by the surface gradients to regions on the substrate surface where select proteins had adsorbed and, most importantly, exhibit appropriate domains which promote subsequent cell adhesion and functions pertinent to new tissue formation. The proposed research is fundamentally different from past and current approaches in that it will develop a new process that will allow high-throughput testing of multiple material formulations of various stoichiometric combinations. This research is expected to achieve the following: (1) elucidate aspects of protein adsorption and adhesion and function of cells on the novel substrates; and (2) establish the potential of these metal oxide substrates as a high-throughput cytocompatibility assessment platform. PUBLIC HEALTH RELEVANCE: With a U.S. Prosthetic Implant market of about $1 billion a year and growing at a rate of 10% a year, any improvement in osseointegration and life of the prosthetic implant will have a drastic economic effect, especially if one takes into consideration that up to 30% of the implants in procedures such as hip replacement do not show appropriate osseointegration. The proposed project aims to improve the number of candidate biomaterials screened for improved osseointegration by investigating the effect of the material surface properties and protein adsorption on osteogenic mesenchymal stem cell behavior, using state of the art surface characterization and gene expression technologies.

描述（由申请人提供）：该项目的总体目标是为基于组合材料科学的生物材料筛选策略奠定基础。这种方法将为基材提供一系列表面特性和成分的微妙变化。这些新型材料配方的功效将在体外使用细胞培养模型进行确定，并通过系统研究生物材料表面化学和形貌的元素组成对间充质干细胞（MSC）分化和与新材料相关的功能的影响。骨形成。中心假设是材料基底的金属氧化物表面调节吸附蛋白质的类型、分布和构象，这些蛋白质指导和调节随后的细胞相互作用和与新组织形成相关的功能。具体目标 1：开发基于钛的金属氧化物基材，其中含有用作植入材料的三种其他金属的梯度。据推测，通过等离子体增强化学气相沉积进行退火，将使用溅射到钛基板上的不同厚度的薄膜产生浓度梯度。具体目标 2：确定吸附在与具体目标 1 相关的研究活动制备的新型材料基质上的精选血清和/或 ECM 粘附蛋白（例如 I 型胶原、纤连蛋白、层粘连蛋白和玻连蛋白）的类型、分布和构象。具体目标 3：评估 MSC 在纳米结构基质上的成骨分化。据推测，粘附后，MSC 迁移将受到表面梯度的影响，迁移到基底表面上已吸附选定蛋白质的区域，最重要的是，MSC 会表现出适当的结构域，促进随后的细胞粘附和与新组织形成相关的功能。拟议的研究与过去和当前的方法有根本的不同，因为它将开发一种新工艺，允许对各种化学计量组合的多种材料配方进行高通量测试。本研究预计将实现以下目标：（1）阐明蛋白质在新型基质上的吸附和粘附以及细胞功能的各个方面； (2) 确定这些金属氧化物底物作为高通量细胞相容性评估平台的潜力。公共健康相关性：美国假体植入市场每年约 10 亿美元，并且以每年 10% 的速度增长，骨整合和假体植入寿命的任何改善都将产生巨大的经济影响，特别是如果考虑到这一点在髋关节置换术等手术中，高达 30% 的植入物没有表现出适当的骨整合。拟议的项目旨在通过利用最先进的表面表征和基因表达技术，研究材料表面特性和蛋白质吸附对成骨间充质干细胞行为的影响，提高筛选出改善骨整合的候选生物材料的数量。