Osteoinductive hybrid hydrogel membranes for in situ bone regeneration in hyperglycemia

In hyperglycemia patients, suffering from insufficient vascularization and vascular network lesion, tissue regeneration, such as bone repair, is limited and maybe delayed by the secondary injury and hyperglycemic microenvironment. Typically, dental therapies involving guided bone regeneration is facing a difficult condition in the patients with diabetes. In this study, a hybrid membrane was endowed with biomimetic function to create an angiogenesis-inductive microenvironment by calcium ion release to overcome the limitations of bone tissue regeneration in diabetic patients. Biomineralized calcium resource was Janus-structured onto the surface of hybrid hydrogel by layer-by-layer technique to enhance vascularization and improve the bone regeneration in this study. The release of calcium ions from mineralized phases was controlled by the solubility of inorganic phases and the degradation of gels, promoting HIF-1α expression and creating a key role in angiogenesis stimulation. With highly enhanced calcium signaling and blood vessel formation, the hybrid hydrogel membranes improved the recruitment, proliferation and differentiation of mesenchymal stem cells and endothelial progenitors, confirmed by the enhancement of microvascular regeneration and new bone formation in the critical-sized calvarial defect in diabetic model in vivo. Our study demonstrates a translational potential of hybrid hydrogels engineered with inorganic minerals for orthopedic applications in hyperglycemia.