Abstract

Bacterial biofilm and intensive inflammation remain great challenge for wound healing. Herein, a multifunctional hydrogel based on gelatin methacryloyl (GelMA) was designed for wound dressing. The mechanical properties of GelMA hydrogel were improved by additional crosslinking with hyaluronic acid aldehyde (HA-CHO), with the compressive modulus were increased over two-fold. Polydopamine-coated cerium dioxide (PDA-CeO2) was loaded into GH hydrogel to enhance its antibacterial properties. Under near-infrared light (NIR) irradiation, the temperature increased by nearly 53 °C, consequently achieving an inhibition rate of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) exceeding 90%. Meanwhile, PDA-CeO2 could efficiently scavenge reactive oxygen species (ROS) and expression of hypoxia-inducible factor-1α (HIF-1α) was suppressed, polarizing macrophages from pro-inflammation M1 to anti-inflammation M2. The expression of M1 biomarker tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was down-regulated nearly three- and five-fold respectively, while the expression of M2 biomarker transforming growth factor-β (TGF-β) and IL-10 was up-regulated over three-fold. Angiogenesis in human umbilical vein endothelial cell (HUVEC) was also enhanced. Besides, 3,4-dihydroxyphenylalanine grafted-fibroblast growth factor receptor-agonistic peptide (DOPA-FAP) was also integrated. It significantly improved fibroblast attachment and elevated the expression of collagen-I (COLI) over three-fold. In vivo experiment manifested the therapeutic effect of GH/DOPA-FAP/PDA-CeO2 hydrogel combining with NIR treatment. On the 15th day, the wound healing rate in infected wounds exceeded 95%. In conclusion, this study presented a smart strategy for wound healing that utilizes the photothermal antibacterial effect and remodels the immune microenvironment.