An Injectable, Adhesive, and Self‐Healing Hydrogel with Inherently Antibacterial Property for Wound Dressing

Abstract

Antibacterial hydrogel has emerged as an excellent candidate for wound dressing with the ability to eliminate infection and promote wound healing. Herein, a dynamic hydrogel was developed by Schiff base reaction of mixed charged polypeptides and oxidized dextran (ODex). Specifically, biodegradable polypeptides of 1‐(propylthio)acetic acid‐3‐butylimidazole‐modified poly(L‐lysine) (PLL‐PBIM) and adipate dihydrazide‐modified poly(L‐glutamic acid) (PLG‐ADH) were achieved with tunable substitution and charge. By mixing with ODex, charged polypeptides of PLL‐PBIM and PLG‐ADH led to an injectable and self‐healing hydrogel in seconds. The injectable and self‐healing performances of the hydrogels were ascribed to the reversible imine and hydrazone bonds formed between polypeptides and ODex. The positive charged hydrogels exhibited over 95% antibacterial activity against E. coli and S. aureus. An optimized balancing of PLG‐ADH and PLL‐PBIM significantly reduced the hemolysis rate and cytotoxicity of hydrogels. Therefore, the dynamic hydrogel with excellent biocompatibility and inherently antibacterial ability could have potential application for wound dressing.This article is protected by copyright. All rights reserved

Advancements and Challenges in Self-Healing Hydrogels for Wound Care

“…The industry's trend toward developing hybrid and composite hydrogels [12,15,52,[57][58][59][60][61][62] highlights the pursuit of materials with enhanced properties through the combination of polymers. Collagen's compatibility with chitosan [10,56] and poly(ethylene glycol) [13] highlights its significance due to its biocompatibility and biodegradability, emphasizing its value in biomedical applications.…”

“…The theory of wound moist healing, an injectable and self-healing hydrogel comprising collagen (COL), chitosan (CS), and oxidation-modified Konjac glucoman-nan (OKGM), which acts as a macromolecular crosslinker to construct dynamic Schiff base bonds [56]. The industry's trend toward developing hybrid and composite hydrogels [12,15,52,[57][58][59][60][61][62] highlights the pursuit of materials with enhanced properties through the combination of polymers. Collagen's compatibility with chitosan [10,56] and poly(ethylene glycol) [13] highlights its significance due to its biocompatibility and biodegradability, emphasizing its value in biomedical applications.…”

“…Dynamic imine bonds, including imides and hydrazones, present another avenue for reversible crosslinking, bolstering the hydrogels' mechanical durability and flexibility, thereby rendering them highly suitable for applications in drug delivery and tissue engineering [2,10,15,57].…”

“…Further innovations have been achieved with hydrogels that utilize Schiff base reactions. For instance, a hydrogel synthesized from 1-(propylthio)acetic acid-3-butylimidazolemodified poly(L-lysine) and adipate dihydrazide-modified poly(L-glutamic acid) with oxidized dextran displays injectable and self-healing qualities, along with over 95% effectiveness in eradicating E. coli and S. aureus [57]. Enhancements in mechanical strength through double-crosslinking have been realized in another hydrogel that combines dynamic Schiff base bonds with photo-induced crosslinking, leading to superior antibacterial effectiveness, tissue adhesion, and wound-healing properties [16].…”

“…Dopamine-functionalized oxidized hyaluronic acid, adipic acid dihydrazide-modified hyaluronic acid, and aldehyde-terminated Pluronic F127 via Schiff base dynamic covalent bonds Injection abilities and mechanical performance testing, self-healing faster than single-network hydrogels, adhesion properties testing [12] Collagen and polyethylene glycol with umbilical cord stem cell factor Rheology, self-shaping and self-healing testing, adhesion strength enhancement, biocompatibility, cellular response, collagen deposition, neovascularization in diabetic rat model [13] Dynamic Schiff base bonds and non-dynamic photo-induced crosslinking Mechanical performance (elastic recovery and tensile modulus), antibacterial capability, tissue adhesion, healing of infectious cutaneous wounds [16] Mixed charged polypeptides and oxidized dextran via Schiff base reaction Injectable and self-healing performances, antibacterial activity tests against E. coli and S. aureus, hemolysis rate, and cytotoxicity assessment [57] Aldehyde-carrageenan with dopamine and zinc ions Fourier transform infrared spectroscopy (FTIR) analysis, rheological tests, antibacterial properties against E. coli, collagen secretion and cell attachment, fibroblast viability [58] Hyaluronate-adipic dihydrazide/aldehyde-terminated Pluronic F127/fucoidan with lactobacillus rhamnosus via dynamic Schiff base reaction Gelation time, mechanical strength, self-healing, and liquid-absorption abilities, anti-super bacteria effect, cytocompatibility and blood compatibility, in vivo wound healing efficacy [59] Poly(aspartic acid) with hydrazide functional groups crosslinked with dialdehyde functionalized polyethylene oxide Antibacterial property, biocompatibility, in vivo burn wound-repairing experiment [64] Thiol-modified poly(gamma-glutamic acid) and oxidized hyaluronic acid via thiol-aldehyde addition reaction…”