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查策略奠定基础。这种方法将为基材提供表面特性和组成的一系列细微变化。这些新型材料制剂的功效将在体外使用细胞培养模型在体外确定，并通过对生物材料表面化学的元素组成和地形对间质干细胞（MSC）分化的元素组成的影响进行系统研究，并与与新骨形成有关的作用。中心假设是材料底物的金属氧化物表面调节吸附蛋白的类型，分布和构象，这些蛋白质直接并调节随后的细胞相互作用以及与新组织形成有关的细胞相互作用以及功能。特定目标1：基于钛的金属氧化物底物，这些钛含有其他三种金属用作植入物材料的梯度。假设，通过血浆增强化学蒸气沉积退火，将使用溅射到Ti底物上的可变厚度的薄膜产生浓度梯度。 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.可以假设，在粘附后，MSC迁移将受到表面梯度与基板表面的区域的影响，其中所选蛋白吸附了所吸附，最重要的是，表现出适当的结构域，这些结构域促进了随后的细胞粘附和与新的组织形成有关的。拟议的研究从根本上与过去和当前方法有所不同，因为它将开发出一个新的过程，该过程将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。这项研究预计将实现以下方面：（1）阐明细胞在新型底物上的蛋白质吸附以及粘附和功能的方面；（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。公共卫生相关性：随着美国的假体植入物市场每年约10亿美元，每年增长10％，骨整合性和假体植入物的寿命的任何改善都将产生巨大的经济影响，尤其是如果有人考虑到诸如hip替换等植入物中最多30％的植入物都不会显示出适当的osseecretaltion。提出的项目旨在通过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，改善筛选筛分的候选生物材料的数量，以改善骨整合性。