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 in vitro fibroblast L929 cell culture study. The results of in vitro and in vivo studies revealed that the prepared antibacterial hydrogels could largely inhibit bacterial growth. The in vivo 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.

Hyaluronic Acid and Controlled Release: A Review

“…However, it has been proven that for open wounds, local or site-specific sustained release of antiseptics and antibiotics from biomaterials is very effective in reducing systemic side effects related to much higher antibiotic dosages taken orally [127]. The unique chemical interactions of HA with other polysaccharides such as inherently antimicrobial chitosan can be used to produce very effective antiseptic materials such as wound gauzes [128]. Their healing and antiseptic properties can be further boosted by encapsulating proper antiseptics or antibiotics in such HA-chitosan hydrogels.…”

Chitosan and Cellulose-Based Hydrogels for Wound Management

“…The in vivo study in a seawater-immersed wound defect model showed that the hydrogels decreased pro-inflammatory factors and promoted anti-inflammatory factors (TGF-β1) in the wound. The hydrogel promoted excellent re-epithelialization, increased the granulation tissue thickness and the density collagen deposition with good antibacterial activity [ 80 ].…”

Recent Advances in Nanomaterial-Based Wound-Healing Therapeutics

“…The new materials are capable of not only preserving the wound environment but also of transferring active compounds to aid in the wound-healing process [14]. In this regard, various wound-dressing products, such as antibacterial creams, ointments, hydrogels, and antibacterial agents in combination with polymers, are currently available and consist mainly of biodegradable materials such as chitosan, hyaluronic acid, collagen, silicon, cellulose, and gelatin [27][28][29][30][31][32].…”