Here we report development of in-situ stable injectable hydrogels for delivery of cells and growth factors based on two precursors, alginate, and collagen/calcium sulfate (CaSO4). The alg/col hydrogels were shear-thinning, injectable through commercially available needles and stable right after injection. Rheological measurements revealed that pre-crosslinked alg/col hydrogels fully crosslinked at 37 °C and that the storage modulus of alg/col hydrogels increased with increasing the collagen content or the concentration of CaSO4. The viscoelastic characteristics and injectability of the alg/col hydrogels were not significantly impacted by the storage of precursor solutions for 28 days. An osteoinductive bone morphogenic protein-2 (BMP-2) loaded into alg/col hydrogels was released in 14 days. Human mesenchymal stem cells (hMSCs) encapsulated in alg/col hydrogels had over 90% viability over 7 days after injection. The DNA content of hMSC-laden alg/col hydrogels increased by 6-37 folds for 28 days, depending on the initial cell density. In addition, hMSCs encapsulated in alg/col hydrogels and incubated in osteogenic medium were osteogenically differentiated and formed a mineralized matrix. Finally, a BMP-2 loaded alg/col hydrogel was used to heal a critical size calvarial bone defect in rats after 8 weeks of injection. The alg/col hydrogel holds great promise in tissue engineering and bioprinting applications.
Bibliographical noteFunding Information:
This research was funded through financial support from NIH grants R01AR057837, U01AR069395, R01AR072613, and R01AR074458 from NIAMS, and DoD grant W81XWH-20-1-0343. Dr. YoungBum Park is in charge of the in vivo study and a co-corresponding author for the animal experiments in this manuscript. The MicroCT (Bruker Skyscan 1276) instrument was purchased using NIH S10 Shared Instrumentation Grant (1S10OD02349701, PI Timothy C. Doyle). All data supporting the findings of this study are available within the paper and its supplementary file.
All Science Journal Classification (ASJC) codes
- Materials Science(all)