An ingeniously multipurpose hydrogel system with sequential release, antioxidant properties, and responsiveness to...

Diabetic bone defects are primarily characterized by significantly impaired bone healing capacity, slow and poor-quality bone repair, and a high risk of nonunion and delayed union. The pathogenesis of diabetic bone defects involves intricate factors, driven by a "malicious network" formed by hyperglycemia and various metabolic disorders it induces, including chronic inflammatory states, oxidative stress, and microvascular complications. The hydrogel system (GZ/V/B@HPP) designed in this study can rapidly release antioxidant nanoparticles GA@ZIF-8 in response to the microenvironment of high-glucose/pH/ROS to "purify" the microenvironment. GZ/V/B@HPP inhibits the generation of ROS and adipogenic differentiation of BMSCs, through PPAR, AMPK and adipocytokine signaling pathways, and successively releases VEGF and BMP-2 to simulate the natural healing process. This study employs a multi-target, comprehensive therapeutic strategy, actively modifying the local pathological microenvironment of the defect through material biology and drug delivery, successfully initiating and completing a high-quality bone regeneration process, offering a novel solution for the treatment of diabetic bone repair.