A sodium alginate/carboxymethyl chitosan dual-crosslinked injectable hydrogel scaffold with tunable softness/hardness for bone regeneration

Recently, injectable dual-crosslinked (DC) hydrogel scaffolds have attracted many attentions as a class of excellent bone regeneration biomaterials with in-situ tunable functions. However, the design of injectable DC hydrogels with cell behavior-compatible network structure and mechanical property remains a bottleneck. Herein, based on the in-situ gelling method, we constructed an injectable CMCS/PEG+SA/CaCl₂ (CPSC) chemical/physical DC hydrogel scaffold with tunable softness/hardness mechanical properties and good biocompatibility. The formation mechanism and properties of the CPSC hydrogel scaffold were investigated by FTIR, XRD, rheometry, and mechanical testing. It is found that proper softness/hardness mechanical properties can be obtained by adjusting the secondary network structure of the hydrogel. The CPSC hydrogel scaffold prepared under optimal conditions can effectively promote cell infiltration, nutrient transport, and the osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs). The in vivo experiments show that the rBMSCs-loaded injectable CPSC hydrogels with appropriate mechanical properties can effectively promote bone reconstruction. This study has provided important guidance for the construction of injectable DC hydrogels with adjustable softness/hardness to promote osteogenesis for bone defect repair.