Multifunctional hydrogel with reactive oxygen species scavenging and photothermal antibacterial activity accelerates infected diabetic wound healing

Abstract

Management of diabetic wound has long been a clinical challenge due to pathological microenvironment of excessive inflammation, persistent hyperglycemia, and biofilm infection caused by overdue reactive oxygen species (ROS) production and defective blood vessels. Herein, a multifunctional hydrogel with ROS scavenging and photothermal antibacterial activity based on oxidized dextran (Odex), gallic acid-grafted gelatin (GAG) and Ferric ion, named OGF, was developed for treatment of infected wound in a diabetic mouse. This hydrogel was double-crosslinked by the dynamically Schiff-base bonds formed between aldehyde groups in Odex and amino groups in GAG and the metal coordination bonds formed between Ferric ion and polyphenol groups or carboxyl groups in GAG, which endowed the resulted OGF hydrogel with well injectable, self-healing and adhesive properties. Due to the high-efficiency photothermal effect of Ferric ion/polyphenol chelate, this hydrogel killed Staphylococcus aureus and Escherichia coli rapidly and completely within 3.5 min under near-infrared light radiation. Furthermore, this composed hydrogel presented good antioxidation, hemostasis and biocompatibility. It also remarkably accelerated the complete re‑epithelialization of Staphylococcus aureus‑infected wound in diabetic mice within 18 days by eliminating infection, mitigating oxidative stress and inflammation, and facilitating angiogenesis. Therefore, the proposed multifunctional hydrogel exerts a great potential for translation in the clinical management of diabetic wounds. STATEMENT OF SIGNIFICANCE: High reactive oxygen species (ROS) levels and vascular defects in diabetic wounds can lead to excessive inflammation, persistent hyperglycemia, biofilm infection and other pathological microenvironments, which can further develop to the chronic wounds. In this study, we designed a multifunctional hydrogel with ROS-scavenging ability and photothermal antibacterial activity for the treatment of infected diabetic wound. As expected, this multifunctional hydrogel dressing highly accelerated the complete re‑epithelialization of Staphylococcus aureus‑infected wound in diabetic mouse by eliminating infection, mitigating oxidative stress and inflammation, as well as facilitating angiogenesis. This work provides a promising therapeutic strategy for infected diabetic wound by inhibition of oxidative stress and biofilm infection.

Keywords: Diabetic wound; Infected wound; Multifunctional hydrogel; Photothermal antibacterial; ROS scavenging.