DNA-Inspired Multi-Functional Double-Cross-Linking Self-Healing Hydrogel Promotes the Healing of Diabetic Wounds

The impaired healing of diabetic wounds caused by microenvironmental imbalances presents a significant clinical challenge. In this study, a deoxyribonucleic acid (DNA)-inspired, self-healing hydrogel-based delivery system-ATG@Exo^Cur-is developed that synergistically promotes diabetic wound healing by modulating multiple pathological processes. This system features a double-crosslinked, self-healing hydrogel derived from natural polysaccharides, which leverages the principle of DNA base-pairing to achieve controlled drug release and mechanical adaptability. Additionally, incorporating exosome-loaded curcumin enhances its physicochemical stability and improves the targeted delivery efficiency. This study demonstrates that ATG@Exo^Cur effectively scavenges reactive oxygen species, suppresses chronic inflammation, promotes angiogenesis, and modulates the immune microenvironment by inducing macrophage polarization toward a pro-repair phenotype. By integrating biomaterial engineering with biological activity, this system overcomes the limitations of monotherapies and offers a novel, highly efficient, and safe approach for treating chronic diabetic wounds.