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

Xinlu Wang,Biao Cheng,Qi Fang,Longbao Feng,Rui Guo,Pengcheng Xu,Zexin Yao

doi:10.3389/fbioe.2019.00360

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.

Highlights

With the extensive use of high-tech weapons, especially precision-guided missiles on the battlefield, the trauma and burns caused by high-energy explosion in naval battle have become the most important and challenging healthcare issues (Zhu et al, 2017; Chen et al, 2019)
The results indicated that O-HACC and N-HACC increased solubility under different pH conditions
The results revealed that the swelling ratios of the oxidized hyaluronic acid (OHA)/Hyaluronic acid (HA)-Adipic dihydrazide (ADH), OHA/hyaluronic acid-hydrazide (HA-ADH)/O-HACC, and OHA/HA-ADH/N-HACC hydrogels in phosphate-buffered saline (PBS) reached 44.47, 6.03, and 10.96, respectively, in the first 2 h (Figure 2B)

Summary

Introduction

With the extensive use of high-tech weapons, especially precision-guided missiles on the battlefield, the trauma and burns caused by high-energy explosion in naval battle have become the most important and challenging healthcare issues (Zhu et al, 2017; Chen et al, 2019). In modern high-tech naval warfare, the unavoidable exposure of open traumas to seawater with high salt, high sodium, and a high abundance of pathogenic bacteria, especially gram-negative bacteria, can cause serious infections and wound-repair difficulties (Zhang et al, 2017). Current traditional antimicrobials such as antibiotics, iodine, silver, and zinc oxide are effective in preventing bacterial infection of skin wounds, but they cause resistance to last-line antibiotics and cause significant damage to vital organs (Chung et al, 2017; Lin et al, 2019). The addition of quaternary amino groups in chitosan greatly enhances the water solubility of chitosan, and quaternized chitosan with antimicrobial activity combines with polyatomic amino groups to form double antimicrobial active groups, which greatly improves its antimicrobial field of application

Objectives

Methods

Results

Conclusion