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 ?5?1 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 CT 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.

Public Health Relevance

Mesenchymal stem cells isolated from bone marrow are promising for musculoskeletal tissue repair, but their clinical use has produced inconsistent results. In this project we will develop new cell- instructive biomaterials that can be used to deliver these adult stem cells and guide them to produce bone-like tissue by providing specific physical and biochemical signals. This work could lead to advances in cell-based therapies for orthopedic medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR071625-02
Application #
9439692
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2017-03-01
Project End
2019-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Texas Engineering Experiment Station
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
847205572
City
College Station
State
TX
Country
United States
Zip Code
77843
Xin, Shangjing; Wyman, Omar M; Alge, Daniel L (2018) Assembly of PEG Microgels into Porous Cell-Instructive 3D Scaffolds via Thiol-Ene Click Chemistry. Adv Healthc Mater 7:e1800160