A Three-in-One Strategy: Injectable Biomimetic Porous Hydrogels for Accelerating Bone Regeneration via Shape-Adaptable Scaffolds, Controllable Magnesium Ion Release, and Enhanced Osteogenic Differentiation.

The repair of bone defects with irregular shapes, particularly in a minimally invasive manner, remains a major challenge. For synthetic bone grafts, injectable hydrogels are superior to conventional scaffolds because they can adapt satisfactorily to the defect margins and can be injected into deeper areas of injury via a minimally invasive procedure. Based on the poly(lactide--glycolide)(PLGA)/1-methyl-2-pyrrolidinone solution reported in our previous study, we successfully synthesized injectable MgO/MgCO@PLGA (PMM) hydrogels, namely, injectable biomimetic porous hydrogels (IBPHs), to accelerate bone regeneration. In addition to exhibiting excellent injectability, PMM hydrogels could transform into porous scaffolds in situ through a liquid-to-solid phase transition and completely fill irregular bone defects via their superb shape adaptability. Moreover, sustainable and steady release of Mg was achieved by regulating the weight ratio of the incorporated MgO and MgCO particles. Via controlled release of Mg, PMM hydrogels significantly promoted proliferation, osteogenic differentiation, migration, and biomineral deposition of immortalized mouse embryonic fibroblasts. More importantly, micro-CT imaging and histological analysis indicated that concomitant with their gradual degradation, PMM hydrogels effectively stimulated in situ bone regeneration in rat calvarial defects with an increase in the bone volume fraction of almost 2-fold compared with that in the control group. These findings suggest that injectable PMM hydrogels can satisfactorily match bone defects and form porous scaffolds in situ and can significantly promote bone regeneration via controllable Mg release. The remarkable features of IPBHs may open a new avenue for the exploration of in situ repair systems for irregular bone defects to accelerate bone regeneration and have great potential for clinical translation.