Calcium-releasing elastic hydrogel scaffolds for <i>in situ</i> bone regeneration

It is significant to endow bone tissue scaffolds with elasticity and the capacity of establishing a bone remodelling microenvironment to thus exploit the endogenous regeneration functions of bone for regenerating critical-sized bone defects. To this end, this work constructed calcium sulphate (CaSL)-loaded silk fibroin (SF)/gelatin elastic hydrogel scaffolds by means of an indirect three-dimensional (3D) printing technique. The results showed that the indirect 3D printing technique was a general method to prepare elastic SF-based composite hydrogel scaffolds. <i>In vitro</i> experiments demonstrated that the as-prepared scaffolds could establish an acidic and high-calcium ion concentration microenvironment, which could mediate the proliferation, migration, and osteogenic differentiation of mesenchymal stem cells (MSCs). Ectopic muscle implant experiments demonstrated that the CaSL-loaded hydrogel scaffolds could stimulate, recruit and capture MSCs and macrophages into scaffolds. Ulnar/cranial bone defect implant results demonstrated that the elasticity of the scaffolds and the microenvironment constructed by CaSL degradation played important roles in mediating the spontaneous growth of the cortical bone.