Effective Wound Healing by Antibacterial and Bioactive Calcium-Fluoride-Containing Composite Hydrogel Dressings...

In this study, we report the development of a hyaluronic acid (HA)-based composite hydrogel containing calcium fluoride (CaF₂) with good biocompatibility and antibacterial properties for multifunctional wound dressing applications. CaF₂ was newly selected for incorporation within HA because it can release both Ca²⁺ and F^- ions, which are well-known ions for affecting cell proliferation and inhibiting bacterial growth, respectively. In particular, an in situ precipitation process enables easy control over the released amount of F^- ions by simply adjusting the precursor solutions (calcium chloride (CaCl₂) and ammonium fluoride (NH₄F)) used for the CaF₂ precipitation. CaF₂ particles were uniformly embedded within a HA-based pure hydrogel using an in situ precipitation process. Through variation of the CaCl₂ and NH₄F concentrations used in the precipitation as well as the precipitation time, composite hydrogels with different ion-release profiles were obtained. By controlling the precipitation time, especially for 10 min and after 30 min, large differences in the ion-release profiles as a function of CaF₂ concentration were observed. A shorter precipitation time resulted in faster release of fluoride, whereas for the 30 min and 1 h samples, sustained ion release was achieved. Colony tests and live/dead assays using Escherichia coli and Staphylococcus aureus revealed a lower density of bacteria on the CaF₂ composite hydrogels than on the pure hydrogel for both strains. In addition, improved cellular responses such as cell attachment and proliferation were also observed for the CaF₂ composite hydrogels compared to those for the pure hydrogel. Furthermore, the composite hydrogels exhibited excellent wound healing efficiency, as evidenced by an in vitro cell migration assay. Finally, monitoring of the wound closure changes using a full-thickness wound in a rat model revealed the accelerated wound healing capability of the CaF₂ composite hydrogels compared with that of the pure hydrogel. Based on our findings, these CaF₂ composite hydrogels show great potential for application as advanced hydrogel wound dressings with antibacterial properties and accelerated wound-healing capabilities.