An injectable conductive multifunctional hydrogel dressing with synergistic antimicrobial, ROS scavenging, and electroactive effects for the combined treatment of chronic diabetic wounds

The hypoxic, hyperglycemic, ischemic and inflammatory at the chronic diabetic wound microenvironment often leads to persistent oxidative stress and dysfunctional immune responses, as evidenced by hindrance of angiogenesis, neuropathy and impaired macrophage M2-type transition. In addition, bacterial infections lead to further exacerbation of chronic inflammatory responses, which severely impedes wound healing. In this study, hydroxypropyl chitosan (HCS) and 2,3,4-trihydroxybenzaldehyde (TBA) hydrogel was prepared via a one-step method, while Fe³⁺ was used to initiate the in-situ oxidative polymerization of pyrrole (Py) in the hydrogel network, that conferred the HCS-TBA@Py hydrogel with excellent electrical conductivity. The outstanding physicochemical properties of the hydrogel, including swelling ability, injectability and electrosensitivity, confirmed its potential for applications in rapid filling of irregular wounds and strain sensors. Meanwhile, HCS-TBA@Py hydrogel can effectively scavenge reactive oxygen species and inhibit bacterial growth. More importantly, the combination of HCS-TBA@Py with electrical stimulation (ES) can effectively enhance the proliferation and migration of endothelial cells, promote axonal growth of nerve cells, rapid angiogenesis and accomplish the phagocytosis of M1 macrophages while realizing the M2 polarization of macrophages, comprehensively and systematically ameliorating the healing of diabetic wounds. This advanced study opens a meaningful way for chronic diabetic wound repair.