In-situ stable injectable collagen-based hydrogels for cell and growth factor delivery

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.

Automated summary

This study developed stable hydrogels for cell and growth factor delivery, demonstrating excellent injectability and biocompatibility. The loaded BMP-2 and hMSCs in the hydrogel showed sustained release and viability, promoting osteogenic differentiation and mineralized matrix formation. In animal experiments, the hydrogel exhibited significant healing effects on bone defects, highlighting its promising applications in tissue engineering and bioprinting.