Injectable adhesive self-healing hyaluronic acid-based hydrogel with microenvironment-responsive metformin delivery and photothermal antibacterial activity for diabetic infected wound healing.

Chronic wounds resulting from diabetes pose a significant hurdle in medical management due to their pathological characteristics such as susceptibility to infection, persistent excessive inflammatory response, abnormal accumulation of reactive oxygen species (ROS), and vascular regeneration dysfunction. To address this series of complex issues, an innovative "smart" hydrogel dressing (Met/L-MPDA/Gel) with microenvironment-responsive metformin delivery capability is synthesized. This hydrogel is engineered by crosslinking phenylboronic acid-functionalized hyaluronic acid with polyvinyl alcohol via dynamic phenylboronate ester bonds, incorporating L-arginine-modified mesoporous polydopamine (L-MPDA) with photothermal properties. Met/L-MPDA/Gel exhibits excellent injectable performance, self-healing property, adhesion ability, and DPPH-scavenging effect. Its glucose-responsive design enables controlled metformin release, significantly enhancing the therapeutic efficacy of metformin in diabetic wound microenvironments. In vitro evaluations demonstrate that Met/L-MPDA/Gel combined with photothermal therapy (PTT) has notable antibacterial and anti-biofilm activities against both E. coli and S. aureus. Additionally, the hydrogel shows excellent biocompatibility, promoted cell migration, scavenged ROS, modulated macrophage polarization, mitigated inflammation, and stimulated vessel formation. In vivo studies reveal that Met/L-MPDA/Gel combined with PTT significantly accelerates diabetic infected wound healing by promoting collagen deposition, eliminating bacteria, alleviating oxidative stress, regulating macrophage polarization, suppressing inflammation, enhancing angiogenesis, and stimulating cellular proliferation. These findings collectively establish Met/L-MPDA/Gel as a promising bio-dressing with significant clinical potential for treating diabetic infected wounds.