Multifunctional microsphere dressings via metal ligand bonding engineering for infectious wound healing

Surgical incision infection is the most common postoperative complication that poses a serious threat to human health. In this work, the iron gallate (GA-Fe) modified hyaluronic acid microspheres (GFe@HAMSs) multifunctional dressings with antibacterial activity, biodegradability, and the ability to promote tissue regeneration for infectious wound healing are prepared via the bonding engineering between bioactive iron ions and ligands from both polyphenol (i.e. gallic acid, GA) and HAMSs matrix. In our strategy, the Fe-HAMS interaction is first constructed, leading to the shrinkage of iron-doped HAMSs (Fe@HAMSs). Then, the addition of GA further tunes the metal-matrix bonding by introducing the competitive equilibrium between Fe-HAMS and Fe-GA chelation, leading to the volume expansion of GFe@HAMSs. The introduction of iron ions can effectively shorten the inflammatory response and reverse the iron-deficient microenvironment, thereby transforming the wound microenvironment into one conducive to tissue regeneration. Benefitting from these bioactive effects of iron ions and the photothermal antibacterial activity of GA-Fe, the GFe@HAMSs significantly accelerate the wound healing process for rat skin-infected wounds by inhibiting the inflammatory response and macrophage polarization and promoting angiogenesis and tissue remodeling. The GFe@HAMSs proposed in this work not only provide a biomaterial for infectious wound healing but also offer a new strategy for designing multifunctional dressing.