Regulating Macrophage Polarization in High Glucose Microenvironment Using Lithium-Modified Bioglass-Hydrogel for Diabetic Bone Regeneration

Diabetes mellitus is a chronic metabolic disease with a proinflammatory microenvironment, causing poor vascularization and bone regeneration. Due to the lack of effective therapy and one-sided focus on the direct angiogenic properties of biomaterials and osteogenesis stimulation, the treatment of diabetic bone defect remains challenging and complex. In this study, using gelatin methacryloyl (GelMA) as a template, a lithium (Li) -modified bioglass-hydrogel for diabetic bone regeneration is developed. It exhibits a sustained ion release for better bone regeneration under diabetic microenvironment. The hydrogel is shown to be mechanically adaptable to the complex shape of the defect. In vitro, Li-modified bioglass-hydrogel promoted cell proliferation, direct osteogenesis, and regulated macrophages in high glucose (HG) microenvironment, with the secretion of bone morphogenetic protein-2 and vascular endothelial growth factor to stimulate osteogenesis and neovascularization indirectly. In vivo, composite hydrogels containing GelMA and Li-MBG (GM/M-Li) release Li ions to relieve inflammation, providing an anti-inflammatory microenvironment for osteogenesis and angiogenesis. Applying Li-modified bioglass-hydrogel, significantly enhances bone regeneration in a diabetic rat bone defect. Together, both remarkable in vitro and in vivo outcomes in this study present an opportunity for diabetic bone regeneration on the basis of HG microenvironment.

Automated summary

This study developed a lithium-modified bioglass-hydrogel that can release ions continuously under diabetic microenvironment, promoting bone regeneration. In vitro experiments demonstrated that the lithium-modified bioglass-hydrogel can enhance cell proliferation and regulate macrophages in a high glucose microenvironment, indirectly stimulating osteogenesis and neovascularization. In vivo experiments showed that the lithium-modified hydrogel significantly enhances bone regeneration in diabetic rat bone defects.