Developing hyaluronic acid-proline-ferric ion cross-linked film for efficient wound healing application

[Display omitted] •A biocompatible HA-Pro-Fe3+ cross-linked film was successfully fabricated.•HA-Pro-Fe3+ cross-linked film exhibited antibacterial and antioxidative property.•HA-Pro-Fe3+ cross-linked film significantly improved skin wound healing. A novel cross-linked film dressing that can accelerate wound healing and guard against bacterial infection was presented in this work. The hyaluronic acid-proline-ferric ion (HA-Pro-Fe3+) film was successfully prepared by physically cross-linking method, which the carboxyl groups of the HA and Pro molecules should be in coordination with Fe3+. The HA-Pro-Fe3+ cross-linked film showed three-dimensional porous structure, appropriate water vapor permeability and swelling property, favorable cytocompatibility and hemocompatibility, antibacterial and antioxidative capability. The results of rat skin wound healing confirmed that HA-Pro-Fe3+ film could accelerate epithelial regeneration and collagen deposition, promote angiogenesis and significantly improve skin wound healing. Elisa analysis indicated that HA-Pro-Fe3+ material could down-regulate the expression of IL-6 and TNF-α, and up-regulate the level of TGF-β1 and VEGF. Given its biocompatibility, antibacterial ability, promotion of cell proliferation and angiogenesis, the wide application of HA-Pro-Fe3+ cross-linked film in wound repair would be anticipated.