Smart glucose-responsive hydrogel with ROS scavenging and homeostasis regulating properties for diabetic bone regeneration

Diabetic patients often suffer from delayed tissue healing and bone metabolism disorder, presenting a significant clinical challenge in the regeneration of diabetic bone defects. Hyperglycemia weakens osteogenesis and angiogenesis and destroys the balance of homeostasis. To solve this problem, a smart glucose-sensitivity sustained-release Resveratrol-loaded hydrogel platform is proposed to restore the function of mesenchymal stem cells. In this study, phenylboronic acid (PBA), known for its unique glucose sensitivity, is grafted onto the methacrylated gelatin (GelMA) chain, enabling the immobilization of Resveratrol (Res) molecules within the hybrid hydrogel through dynamic borate bond formation. Both in vivo and in vitro findings demonstrate that this hydrogel platform effectively scavenges excessive reactive oxygen species, ameliorates inflammation, modulates macrophage polarization, and enhances osteogenesis by activating the PI3K/AKT/GSK-3β signaling pathway. Collectively, all results suggest that this novel glucose-responsive hydrogel platform may be a potential therapy for diabetic bone regeneration.