Osteoimmunomodulatory injectable Lithium-Heparin hydrogel with Microspheres/TGF-β1 delivery promotes M2 macrophage polarization and osteogenesis for guided bone regeneration

Abstract

When bone injury occurs, immune cells including macrophages, neutrophils, and T lymphocytes are recruited and participate in immunomodulatory and bone dynamics regulation in injury sites, and thus manipulate the immune cells to generate a favorable osteo-immune environment is a promising approach for bone repair. Here we report a bone regeneration strategy using an advanced osteoimmunomodulatory biomaterial platform that loads TGF-β1-containing gelatin-heparin microspheres (MS/TGF-β1) into an injectable lithium-heparin hydrogel (Li-gel), wherein Li-gel acts not only as delivery carrier for MS/TGF-β1, but also as Li ions release matrix promoting osteogenesis, while the TGF-β1 release is to guide macrophage for M2 polarization. Moreover, both in vitro and in vivo studies show that Li-gel@MS/TGF-β1 enhances osteogenesis and angiogenesis via TGF-β/Snail pathway, and improves the new bone formation. Taken together, this newly developed osteoimmunomodulatory biomaterial platform with guided bone regeneration via promoting M2 macrophage polarization and osteogenesis can be a promising approach for bone repair and regeneration.