Osteoinductive Microgel-Based Scaffolds for hMSC Delivery

项目摘要/摘要 据估计，美国每年进行近150万例骨移植手术，而这 随着人口老龄化，这一数字预计还会上升。人骨髓间充质干细胞(HMSC)骨组织 长期以来，工程学一直被认为是解决这一问题和自体骨移植局限性的有希望的解决方案， 但hMSCs的临床前和临床试验并没有达到预期。因此，这个项目的目标是开发 一种可携带hMSCs并提高其治疗效果的骨诱导水凝胶支架 骨修复。这个项目的方法是基于可调的聚乙二醇基水凝胶 微球作为细胞教育支架的构建块。随后，将进行体内测试，以 测试这些指导细胞的生物材料是否能对骨缺损产生治疗上的显著效果 治愈。该项目有两个具体目标：(目标1)微凝胶支架，将通过点击组装 化学，将通过α5β1整合素使细胞接触并通过 机械转导。(目标2)将骨诱导微凝胶支架与hMSCs结合，然后 在裸鼠股骨缺损区模型上进行测试。骨愈合将通过µCT和组织学和 与临床基准进行比较，确定支架与hMSCs的相对疗效。研究团队 和环境：这个项目横跨德克萨斯A&M大学生物医学工程系， 德克萨斯农工大学健康科学中心的再生医学研究所。它将由丹尼尔·阿尔热博士领导 (PI)和Carl Gregory博士(Co-I)。阿尔热博士是生物医学工程系的助理教授 拥有开发用于细胞输送的水凝胶生物材料的专业知识。格雷戈里博士是麻省理工学院 再生医学研究所，拥有hMSCs和骨组织工程方面的专业知识。

PROJECT SUMMARY/ABSTRACT It is estimated that nearly 1.5 million bone grafting procedures are performed annually in the U.S., and this number is expected to rise as our population ages. Human mesenchymal stem cell (hMSC) based bone tissue engineering has long been heralded as a promising solution to this problem and the limitations of bone autografts, but preclinical and clinical trials with hMSCs have not met expectations. Thus, the goal of this project is to develop an osteoinductive hydrogel-based scaffold that can deliver hMSCs and improve their therapeutic efficacy for bone repair. The approach for this project is based on using tunable poly(ethylene glycol)-based hydrogel microspheres as building blocks for cell-instructive scaffolds. Subsequently, in vivo testing will be performed to test whether these cell-instructive biomaterials can induce a therapeutically significant effect on bone defect healing. This project has two specific aims: (Aim 1) Microgel scaffolds, which will be assembled with click chemistry, will be engineered to induce hMSC osteogenesis by engaging cells through α5β1 integrins and by mechanotransduction. (Aim 2) Osteoinductive microgel-based scaffolds will be combined with hMSCs and then tested in a nude mouse femoral defect model. Bone healing will be evaluated by µCT and histology and compared to a clinical benchmark to determine the relative efficacy of the scaffolds and hMSCs. Research team and environment: This project spans the Department of Biomedical Engineering at Texas A&M University and the Institute for Regenerative Medicine in the Texas A&M Health Science Center. It will be led by Dr. Daniel Alge (PI) and Dr. Carl Gregory (Co-I). Dr. Alge is an assistant professor in the Department of Biomedical Engineering with expertise in developing hydrogel biomaterials for cell delivery. Dr. Gregory is an associate professor in the Institute for Regenerative Medicine with expertise in hMSCs and bone tissue engineering.