Preparation of Antimicrobial Hyaluronic Acid/Quaternized Chitosan Hydrogels for the Promotion of Seawater-Immersion Wound Healing

Abstract

Wound immersion in seawater with high salt, high sodium, and a high abundance of pathogenic bacteria, especially gram-negative bacteria, can cause serious infections and difficulties in wound repair. The present study aimed to prepare a composite hydrogel composed of hyaluronic acid (HA) and quaternized chitosan (QCS) that may promote wound healing of seawater-immersed wounds and prevent bacterial infection. Based on dynamic Schiff base linkage, hydrogel was prepared by mixing oxidized hyaluronic acid (OHA) and hyaluronic acid-hydrazide (HA-ADH) under physiological conditions. With the addition of quaternized chitosan, oxidized hyaluronic acid/hyaluronic acid-hydrazide/quaternized chitosan (OHA/HA-ADH/O-HACC and OHA/HA-ADH/N-HACC) composite hydrogels with good swelling properties and mechanical properties, appropriate water vapor transmission rates (WVTR), and excellent stability were prepared. The biocompatibility of the hydrogels was demonstrated by <i>in vitro</i> fibroblast L929 cell culture study. The results of <i>in vitro</i> and <i>in vivo</i> studies revealed that the prepared antibacterial hydrogels could largely inhibit bacterial growth. The <i>in vivo</i> study further demonstrated that the antibacterial hydrogels exhibited high repair efficiencies in a seawater-immersed wound defect model. In addition, the antibacterial hydrogels decreased pro-inflammatory factors (TNF-α, IL-1β, and IL-6) but enhanced anti-inflammatory factors (TGF-β1) in wound. This work indicates that the prepared antibacterial composite hydrogels have great potential in chronic wound healing applications, such as severe wound cure and treatment of open trauma infections.