Bioadhesive supramolecular polymer/hyaluronic acid hydrogel with sustained release of zinc ions and dexamethasone for diabetic wound healing

Diabetic patients often struggle with wound healing and are at higher risk of infections, necessitating the development of a stretchable, adhesive hydrogel dressing with antibacterial and angiogenesis-promoting properties. In this study, we synthesized a series of adhesive, antibacterial and anti-inflammatory hydrogels using free radical polymerization with materials including methacrylated hyaluronic acid (HAMA), N-[tris(hydroxymethyl) methyl]acrylamide (THMA), and 3-(bis(pyridin-2-ylmethyl)amino)propyl methacrylate (DPAMA). By leveraging the strong affinity of zinc(II)-dipicolylamine coordination complexes for the phosphorylated groups in dexamethasone sodium phosphate (DMSP), Zn2+ and DMSP were successfully incorporated into the hydrogel. The results demonstrated that the hydrogels possessed excellent adhesiveness and mechanical properties, enabling them to adhere closely to the skin while remaining easily removable without causing trauma. Antibacterial tests demonstrated significant inhibitory effects against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), attributed to the slow release of Zn2+, which effectively suppressed bacterial growth. Additionally, the slow release of DMSP provided strong anti-inflammatory effects. The DHTDZ2 hydrogel, containing 1.5 mg/mL Zn2+ and 4 mg/mL DMSP, significantly accelerated the healing of full-thickness skin wounds. In vitro angiogenesis, immunofluorescence, and immuno-histochemical results further confirmed that the DHTDZ2 hydrogel promoted angiogenesis and reduced the expression of pro-inflammatory factors. In summary, the hydrogel is an effective wound healing dressing that can reduce wound infections and inflammation.