Dual-network hydrogel loaded with octreotide promotes diabetic wound healing by inhibiting cGAS-STING pathway

Background Diabetic wound, a severe complication of diabetes mellitus, are characterized by chronic inflammation, impaired angiogenesis, and prolonged wound healing. As a somatostatin analog, octreotide (Oct) has been previously found to promote wound healing. However, its application is limited by its low stability and susceptibility to enzymatic degradation. Methods Octreotide was incorporated into a dual-network hydrogel (CS-PBA/PVA/PA) with a 3D porous structure using a one-pot method to form CPP@Oct. Its physicochemical properties, drug release behavior, and biological effects were evaluated in vitro and in vivo. Network pharmacology, Western blotting, immunohistochemistry, and animal models (db/db mice and diabetic rats) were used to investigate the mechanisms and therapeutic effects of CPP@Oct. Results The unique design of the CPP@Oct double-network hydrogel demonstrates exceptional swelling capacity, self-healing properties, and controlled drug release characteristics in high-glucose environments. It significantly reduced inflammatory markers and reactive oxygen species (ROS), promoted angiogenesis (increased CD31, VEGF), and enhanced mitochondrial function. In animal models, CPP@Oct accelerated wound closure, increased collagen deposition, and improved vascular density. Mechanistically, it suppressed the cGAS-STING pathway, alleviating inflammation and promoting tissue repair. Conclusion CPP@Oct hydrogel offers a promising therapeutic strategy for diabetic wound by simultaneously addressing inflammation, angiogenesis, and tissue repair through cGAS-STING pathway inhibition. Its dual-network design provides a versatile platform for targeted drug delivery in wound healing applications.