Dual cross-linked organic-inorganic hybrid hydrogels accelerate diabetic skin wound healing

Limited therapeutic options are available for healing chronic non-self-healing diabetic wounds, which are characterized by bacterial infection as well as a hypoxic microenvironment. Here, we report a simple and efficient strategy to generate a multifunctional organic–inorganic hybrid hydrogel to simultaneously overcome these problems. This hybrid hydrogel is composed of a dual cross-linked silk fibroin (SF) network with hemoglobin (Hb) and gallium (Ga) (referred to as SF/Hb/Ga). Material characterization of hybrid hydrogels and investigations of their antibacterial properties and protease-dependent release behaviors were carried out to confirm their multiple functions as wound dressings. In vitro experiments showed that the SF-based hydrogel significantly promoted cell proliferation. Hb, as a peroxidase, could decompose H2O2 to O2 to achieve a suitable normoxic microenvironment for diabetic wound healing. In vivo experimental results showed that the SF/Hb/Ga hybrid hydrogel accelerated the three phases of tissue repair and completely healed bacterially infected diabetic wounds within 15 days. Overall, the present hybrid strategy offers a new opportunity to produce multifunctional dressing materials for the management of infected diabetic wounds.