Mechanically reinforced injectable bioactive nanocomposite hydrogels for in-situ bone regeneration

Gelatin-methacryloyl (GelMA) has received extensive attention in tissue engineering because of its low antigenicity, suitable biodegradability, and similarity to ECM. However, it is still a challenge to induce in-situ bone regeneration for bone defects due to the absence of osteogenic factors or other mineral ions. In this study, a novel injectable organic–inorganic nanocomposite GelMA hydrogel system doped Sr-substituted xonotlite (Sr-CSH) nanofibers was developed. The integration of Sr-CSH nanowires improved the mechanical property of GelMA hydrogels. In addition, GelMA/Sr-CSH hydrogels facilitated cell adhesion, proliferation, ALP activity and the expression of osteogenic genes (BSP, OPN and OCN) and angiogenesis genes (VEGF, ANG-1 and CD31) by activating the ERK/p38 signaling pathway in vitro. Moreover, in vivo results of in-situ bone regeneration in rat calvarial defects model demonstrated that the incorporation of Sr-CSH nanowires could apparently accelerate new bone formation of GelMA. Overall, the prepared injectable organic–inorganic nanocomposite of GelMA/Sr-CSH hydrogel system has great potential for in-situ bone regeneration of bone defect area.