Osteoinductive Microgel-Based Scaffolds for hMSC Delivery

项目概要/摘要 据估计，在美国每年进行近150万例骨移植手术，而这 随着人口老龄化，预计这一数字还会上升。基于人间充质干细胞（hMSC）的骨组织 工程学长期以来被认为是解决这个问题和自体骨移植局限性的有希望的方法， 但是hMSC的临床前和临床试验没有达到预期。因此，该项目的目标是开发 一种基于水凝胶的骨诱导支架，其可以递送hMSC并改善其对以下疾病的治疗功效： 骨修复该项目的方法是基于使用可调聚（乙二醇）基水凝胶 微球作为细胞指导性支架的构建块。随后，将进行体内试验， 测试这些细胞指导性生物材料是否可以对骨缺损诱导治疗显著效果 治愈该项目有两个具体目标：（目标1）微凝胶支架，这将是组装点击 将通过α5β1整合素与细胞结合， 机械传导(Aim 2）骨诱导微凝胶基支架将与hMSC组合，然后 在裸鼠股骨缺损模型中测试。将通过µCT和组织学评价骨愈合， 与临床基准进行比较，以确定支架和hMSC的相对功效。研究团队 和环境：该项目跨越德克萨斯A&M大学生物医学工程系， 德克萨斯A&M健康科学中心的再生医学研究所。它将由丹尼尔阿尔奇博士领导 (PI)Carl Gregory博士（Co-I）Alge博士是生物医学工程系的助理教授 在开发用于细胞输送的水凝胶生物材料方面拥有专业知识。格雷戈里博士是一名副教授， 再生医学研究所，在hMSCs和骨组织工程方面拥有专业知识。

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.