A pH and Glucose Dual-Responsive Injectable Chitosan/ε-Polylysine Hydrogel with Inherent Antibacterial and Antioxidant Activities for Diabetic Wound Healing

Abstract Diabetic wounds reside in a sustained hyperglycemic microenvironment, inducing excessive reactive oxygen species accumulation and bacterial infection, which prolongs the inflammatory phase and hinders wound healing. To address this issue, we constructed a dual-responsive hydrogel dressing composed of tannic acid (TA)-modified chitosan (CS) and 4-carboxyphenylboronic acid (CPBA)-grafted ε-polylysine (EPL), via the integration of dynamic covalent bonds (boronate ester bonds), hydrogen bonds, and multiple noncovalent interactions. This design endows the hydrogel with dual responsiveness to both the acidic and hyperglycemic microenvironments characteristic of diabetic wounds. In vitro assays demonstrated that the hydrogel achieved over 97.0% scavenging rates against both DPPH and ABTS radicals, and exhibited antibacterial rates of up to 99.0% against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus, along with excellent cytocompatibility. In addition, in a streptozotocin (STZ)-induced diabetic rat wound model, the wound closure rate reached 97.9% by day 14. Histological analyses further confirmed that the dressing might adapt to the diabetic wound microenvironment, which could help re-epithelialization of the injured wounds and restoration of epidermal thickness to near physiological levels. This multifunctional hydrogel offers a promising strategy for diabetic wound repair research.