Gelatin/sodium alginate composite hydrogel with dynamic matrix stiffening ability for bone regeneration

Bone regeneration is largely affected by mechanical cues in the surrounding microenvironment, and natural new bone formation is an uninterrupted stiffening physiological process. Although cells biological behaviors can be regulated by the dynamic mechanical microenvironment, it is still unclear how dynamic matrix stiffening influences mesenchymal stem cells (MSCs) differentiation and bone formation. In this study, static and dynamic stiffening hydrogels were prepared to evaluate the activity and osteogenic differentiation of MSCs in vitro and the repair ability of calvarial defects in vivo. It was found that the dynamic hydrogel (Dynamic) could be uninterrupted stiffened from 14.63 ± 1.18 kPa to 68.37 ± 4.99 kPa within 7 days. The stiffness of static hydrogels was 10.20 ± 2.39 kPa (Low) and 66.30 ± 4.40 kPa (High). The results indicated that the Dynamic hydrogel promoted the osteogenic differentiation of MSCs compared with the Low and High hydrogels. Notably, in calvarial defect model, the Dynamic group could enhance bone regeneration and promote angiogenesis. The dynamic stiffening hydrogel can promote the bone formation and angiogenesis by activating the extracellular matrix remodeling, which is a potential regeneration composite material for bone defect repair. This strategy for mechanically modifying hydrogel with dynamic stiffening may help to understand how dynamic matrix mechanics guide stem cell fate and bone regeneration.