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

• 批准号: 8199807
• 负责人: Chelsea M Magin
• 金额: $ 4.84万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8199807
• 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

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. PUBLIC HEALTH RELEVANCE: The aim of this proposal is to engineer an improved, bioactive bone graft material for repairing bone defects resulting from congenital anomalies, trauma, infection and cancer. My approach is to investigate the mechanisms for how cells respond to dynamic biophysical cues, such as topography. The results of the proposed research will lead to the creation of improved 3-dimensional synthetic matrices that will act as scaffolds to recruit cells from surrounding tissues and promote natural bone regeneration.

描述（由申请人提供）：临床外科医生在重建由先天异常、创伤、感染和/或肿瘤切除引起的骨缺损时，选择数量有限。目前的骨移植植入技术和材料均存在局限性。因此，我的目标是通过研究人类间充质干细胞 (hMSC) 如何从其微环境接收信息来改进骨移植材料，从周围组织招募细胞并促进成骨分化，这是天然骨再生过程的一部分。拓扑线索已被证明可以影响 hMSC 的细胞粘附、运动、增殖、蛋白质表达、基因调控和分化。 Bowman-Anseth 实验室开发的基于硫醇烯的光聚合方案将用于制造含有细胞粘附模拟物以及酶促和光降解连接的生物材料，从而允许使用精确的空间侵蚀创建地形。拟议的研究旨在通过研究如何将地形线索纳入包含细胞粘附模拟物和酶促降解连接的聚合物支架中，从而影响成骨分化，从而设计改进的骨移植材料。我假设分化将取决于其微环境的动态变化，这将通过光不稳定化学来实现。概述了两个具体目标： 目标 1：识别硫醇烯聚合物支架中促进 hMSC 成骨分化的地形特征和空间排列。目标 2：检查实时改变地形特征的空间排列对成骨分化的影响。 这些目标的完成将显着增进我们对地形如何诱导 MSC 分化机制的理解。这种聚合物系统和方法的多功能性使我们能够针对 hMSC 培养进行独特的实验，并提高我们对材料系统的理解，这些材料系统可以轻松地针对基于干细胞输送或归巢的组织再生应用进行定制。 公共健康相关性：该提案的目的是设计一种改进的生物活性骨移植材料，用于修复先天异常、创伤、感染和癌症引起的骨缺损。我的方法是研究细胞如何响应动态生物物理线索（例如地形）的机制。拟议研究的结果将导致创建改进的 3 维合成基质，该基质将充当支架，从周围组织中招募细胞并促进天然骨再生。