Hydrogel Scaffolds with Engineered Dynamically Tunable Topographies for hMSC Diff

具有用于 hMSC Diff 的工程动态可调拓扑的水凝胶支架

基本信息

批准号：
8333062
负责人：
Chelsea M Magin
金额：
$ 5.05万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2013-08-16
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8333062
关键词：
3-Dimensional Adverse effects Allografting Autologous Autologous Transplantation Biochemical Biocompatible Materials Bone Regeneration Bone Tissue Bone Transplantation Cadaver Cell Adhesion Cell Culture Techniques Cells Chemistry Clinical Complex Cues Defect Development Engineering Environment Excision Extracellular Matrix Gene Expression Regulation Goals Growth Harvest Homing Human Hydrogels Infection Knowledge Laboratories Lead Malignant Neoplasms Mesenchymal Stem Cells Methods Nanotopography Operative Surgical Procedures Pathway interactions Plague Polymers Preparation Process Prosthesis Recruitment Activity Research Risk Scheme Site Stem cells Structure Sulfhydryl Compounds Surface Surgeon System Techniques Testing Time Tissue Engineering Tissues Transplanted tissue Trauma Work base bone cell motility design disease transmission high risk implantation improved interest osteogenic photopolymerization protein expression research study scaffold self-renewal stem cell differentiation tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): Clinical surgeons have a limited number of options when reconstructing bone defects that result from congenital anomalies, trauma, infection and/or oncologic resection. Current bone-graft implantation techniques and materials each have limitations. For this reason, I aim to improve bone grafting materials that will recruit cells from the surrounding tissue and promote osteogenic differentiation, part of the natural bone regeneration process, by investigating how human mesenchymal stem cells (hMSCs) receive information from their microenvironments. Topographic cues have been shown to influence cell adhesion, motility, proliferation, protein expression, gene regulation and differentiation of hMSCs. A thiol-ene based photopolymerization scheme developed in the Bowman-Anseth laboratories will be used to create biomaterials containing cell adhesion mimics and enzymatically and photo-degradable linkages that allow for the creation of topographies using precise spatial erosion. The proposed research aims to engineer improved bone grafting materials by investigating how incorporating topographic cues into a polymer scaffold that contains cell adhesion mimics and enzymatically degradable linkages influences osteogenic differentiation. I hypothesize that differentiation will depend on dynamic changes in their microenvironment that will be achieved through the photolabile chemistry. Two specific aims are outlined: Aim 1: Identify topographic features and spatial arrangements in thiol-ene polymer scaffolds that promote osteogenic differentiation of hMSCs. Aim 2: Examine the effects of changing the spatial arrangement of topographic features in real-time on osteogenic differentiation. Completion of these aims will significantly advance our understanding of the mechanisms for how topography induces MSC differentiation. The versatility of this polymer system and approach allows us to conduct unique experiments for hMSC culture and improve our understanding of material systems that can be easily tailored for tissue regeneration applications based on stem cell delivery or homing.

描述（由申请人提供）：当重建先天性异常，创伤，感染和/或肿瘤学切除术导致的骨缺陷时，临床外科医生的选择有限。当前的骨移植技术和材料各有局限性。因此，我旨在通过研究人类间充质干细胞（HMSC）如何从其微环境中获得信息，从而改善将从周围组织中募集细胞并促进成骨分化的一部分（自然骨再生过程的一部分）的骨移植材料。已显示地形线索会影响细胞粘附，运动，增殖，蛋白质表达，基因调节和HMSC的分化。在Bowman-Anseth实验室中开发的基于硫醇 - 烯基的光聚合方案将用于创建包含细胞粘附模拟的生物材料模拟物和酶和降解链接，从而可以使用精确的空间侵蚀来创建地形。拟议的研究旨在通过研究将地形线索纳入包含细胞粘附模拟的聚合物支架中，从而改善骨移植材料，并将酶促降解的链接影响成骨分化。我假设分化将取决于其微环境的动态变化，这将通过光片化学实现。概述了两个具体目标：目标1：在硫醇 - 烯聚合物支架中确定地形特征和空间排列，以促进HMSC的成骨分化。目标2：检查实时更改地形特征的空间排列对成骨分化的影响。这些目标的完成将大大提高我们对地形如何诱导MSC分化的机制的理解。这种聚合物系统和方法的多功能性使我们能够对HMSC培养进行独特的实验，并提高我们对材料系统的理解，这些系统可以轻松根据干细胞输送或归纳而定制为组织再生应用。