Osteogenic Hydrogel Niches to Promote hMSC Migration and Differentiation

成骨水凝胶生态位促进 hMSC 迁移和分化

• 批准号: 8197724
• 负责人: KRISTI S. ANSETH
• 金额: $ 34.8万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197724
• 关键词: 3-Dimensional; Adverse effects; Area; Attention; Autologous; Biocompatible; Biocompatible Materials; Biological; Bone Regeneration; Bone Transplantation; Cadaver; Calvaria; Cell Adhesion; Cells; Cellular Infiltration; Clinical; Cues; Defect; Deposition; Development; Engineering; Epitopes; Excision; Extracellular Matrix; Future; Growth Factor; Home environment; Human; Hydrogels; Immigration; In Vitro; Infection; Injectable; Invaded; Laboratories; Malignant Neoplasms; Mesenchymal Stem Cells; Minerals; Modification; Movement; Natural regeneration; Operative Surgical Procedures; Osteogenesis; Pathway interactions; Patients; Plague; Platelet-Derived Growth Factor; Polymers; Preparation; Process; Prosthesis; Rattus; Recruitment Activity; Research; Risk; Scheme; Signal Transduction; Site; Sulfhydryl Compounds; Surgeon; System; Techniques; Testing; Tissue Engineering; Tissues; Transplanted tissue; Trauma; Work; allogenic bone transplantation; base; bone; bone mass; bone repair material; cell motility; controlled release; crosslink; design; disorder risk; implantation; improved; in vivo; injured; migration; neuronal cell body; osteogenic; photopolymerization; polymerization; protein aminoacid sequence; public health relevance; repaired; scaffold; success; technique development; tissue regeneration; tool

DESCRIPTION (provided by applicant): There are a limited number of options for clinical surgeons who are faced with reconstructing bone defects that result from congenital anomalies, trauma, infection, and oncologic resection. Current grafting techniques and materials each have their own limitations and drawbacks. For this reason, we aim to create improved bone grafting materials that will act as scaffolds to recruit cells from surrounding tissues and promote natural bone regeneration processes. Using a versatile and robust thiol-ene polymerization scheme developed in the Anseth and Bowman laboratories, we are able to create 3-dimensional matrices containing simple cell adhesion mimics and enzymatically-degradable linkages. As a result, these materials support cellular infiltration and are replaced as new tissue is formed by the body. The research proposed herein will aim to engineer these grafting materials for bone regeneration purposes, first by increasing the ability of cells from the body to migrate into these materials, and then by incorporating signals that tell the invading cells to become bone. Three specific aims are outlined: Aim I: Identify biological epitopes and functionalities that influence the rate of migration of cells into and through thiol-ene polymer scaffolds. Aim II: Develop thiol-ene polymer scaffolds that promote osteogenic differentiation and deposition of a mineralized matrix. Aim III: Demonstrate the ability of injectable polymer scaffolds developed in Aims I & II to promote bone regeneration in vivo. Successful completion of these Aims should significantly advance our understanding of how to design synthetic polymer scaffolds to enhance natural bone regeneration processes, and this material platform should be readily tailored for applications towards regenerating tissues beyond bone, as well as providing specific advantages for future directions in the design of cell delivery vehicles. PUBLIC HEALTH RELEVANCE: The Anseth Group aims to develop synthetic materials for repairing bone defects resulting from congenital anomalies, trauma, infection, and cancer. Our approach is to create 3-dimensional matrices that will act as scaffolds to recruit cells from surrounding tissues and promote natural bone regeneration processes, creating an improved and bioactive bone graft material.

描述（由申请人提供）：面对先天性异常，创伤，感染和肿瘤切除术导致的骨缺损的临床外科医生的选择有限。当前的移植技术和材料都有自己的局限性和缺点。因此，我们旨在创建改进的骨移植材料，将其充当支架，以募集周围组织中的细胞并促进自然骨再生过程。使用在Anseth和Bowman实验室中开发的多功能且坚固的硫醇 - 烯聚合方案，我们能够创建包含简单细胞粘附模拟的三维矩阵，并具有酶促链接。结果，这些材料支持细胞浸润，并因身体形成新的组织而取代。本文提出的研究将首先通过提高细胞从体内迁移到这些材料的能力，然后结合信号来设计这些嫁接材料，以实现骨骼再生目的，然后通过告诉入侵细胞成为骨骼的信号。概述了三个具体目标：目标I：确定影响细胞迁移速率和通过硫醇 - 烯聚合物支架迁移速率的生物学表位和功能。 AIM II：开发硫醇 - 烯聚合物支架，以促进矿化基质的成骨分化和沉积。 AIM III：证明在Aim I＆II中开发的可注射聚合物支架在体内促进骨骼再生的能力。这些目标的成功完成应大大提高我们对如何设计合成聚合物支架以增强自然骨再生过程的理解，并且应轻松地针对将骨骼以外的组织重新生成的组织进行适应，并为未来的细胞输送车辆设计提供特定的优势。 公共卫生相关性：ANSETH集团旨在开发合成材料，以修复先天异常，创伤，感染和癌症导致的骨缺损。我们的方法是创建三维矩阵，该矩阵将充当支架，以募集周围组织中的细胞并促进自然骨再生过程，从而产生改善和生物活性的骨移植物质。