Osteoinductive Microgel-Based Scaffolds for hMSC Delivery
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PROJECT SUMMARY/It is estimated that nearly 1.5 million bone grafting procedures are performed annually in the U.S., and thisnumber is expected to rise as our population ages. Human mesenchymal stem cell (hMSC) based bone tissueengineering 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 developan osteoinductive hydrogel-based scaffold that can deliver hMSCs and improve their therapeutic efficacy forbone repair. The approach for this project is based on using tunable poly(ethylene glycol)-based hydrogelmicrospheres as building blocks for cell-instructive scaffolds. Subsequently, in vivo testing will be performed totest whether these cell-instructive biomaterials can induce a therapeutically significant effect on bone defecthealing. This project has two specific aims: (Aim 1) Microgel scaffolds, which will be assembled with clickchemistry, will be engineered to induce hMSC osteogenesis by engaging cells through α5β1 integrins and bymechanotransduction. (Aim 2) Osteoinductive microgel-based scaffolds will be combined with hMSCs and thentested in a nude mouse femoral defect model. Bone healing will be evaluated by µCT and histology andcompared to a clinical benchmark to determine the relative efficacy of the scaffolds and hMSCs. Research teamand environment: This project spans the Department of Biomedical Engineering at Texas A&M University andthe 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 Engineeringwith expertise in developing hydrogel biomaterials for cell delivery. Dr. Gregory is an associate professor in theInstitute for Regenerative Medicine with expertise in hMSCs and bone tissue engineering.
