A Hybrid Injectable and Self-Healable Hydrogel System as 3D Cell Culture Scaffold

Cell therapies have great potential for the treatment of many different diseases, while the direct application of cells to the targeted location leads to limited therapeutic outcomes due to the low cell engraftment and cell survival rate. Injectable hydrogels have been developed to facilitate cell delivery; however, those currently developed hydrogel systems still face the limited cell survival rate. Here, an injectable and self-healable hydrogel is reported through the combination of hyperbranched PEG-based multi-hydrazide macro-crosslinker (HB-PEG-HDZ) and aldehyde-functionalized hyaluronic acid (HA-CHO), with gelatin added to increase the crosslinking density and cell activity. The hydrogels can be formed only in 7 s due to the relatively high content of the functional end groups. The reversible crosslinking mechanism between the hydrazide and aldehyde groups endows the hydrogel with shear-thinning and self-healing properties. The hydrogels with gelatin exhibit relatively better mechanical properties and cell activity. The hydrogels can improve the survival, attachment, and engraftment of injected cells due to the rapid sol-gel transition, which can promote an enhanced regenerative response.