Efficiency of Multifunctional Antibacterial Hydrogels for Chronic Wound Healing in Diabetes: A Comprehensive Review

Abstract

Diabetic chronic wounds or amputation, which are complications of diabetes mellitus (DM), are a cause of great suffering for diabetics. In addition to the lack of oxygen, elevated reactive oxygen species (ROS) and reduced vascularization, microbial invasion is also a critical factor that induces non-healing chronic diabetic wounds, ie, wounds still remaining in the stage of inflammation, after which the wound tissue begins to age and becomes necrotic. To clear up the infection, alleviate the inflammation in the wound and prevent necrosis, many kinds of hydrogel have been fabricated to eliminate infections with pathogens. The unique properties of hydrogels make them ideally suited to wound dressings because they provide a moist environment for wound healing and act as a barrier against bacteria. This review article will mainly cover the recent developments and innovations of antibacterial hydrogels for diabetic chronic wound healing.

Keywords: antibacterial; diabetic chronic wound; hydrogel; infection; inflammation; wound dressing.

Graphical abstract

Figure 1

An illustration of how wounds heal and the major differences between an acute wound and diabetic chronic wound. Reprinted from Tan CT, Liang K, Ngo ZH, Dube CT, Lim CY. Application of 3D bioprinting technologies to the management and treatment of diabetic foot ulcers. Biomedicines. 2020;8:10. Creative Commons Attribution License.

Figure 2

An illustration of major factors that contribute to the pathophysiology of diabetic chronic wounds.

Figure 3

The process of making antibacterial hydrogel. (A) Schematic diagram of the SNP_ECHG fabrication procedures. Chitosan nanoparticles loaded with EGF were first prepared through a modified emulsification method (a-b), following the production of CNPE, AgNO₃ was added to a chitosan-PVA solution, which was vigorously stirred afterward (c), an eight-cycle freezing/thawing procedure was performed on the polymeric mixture (d) to obtain SNP_ECHG (e); Reproduced from Lee YH, Hong YL, Wu TL. Novel silver and nanoparticle-encapsulated growth factor co-loaded chitosan composite hydrogel with sustained antimicrobility and promoted biological properties for diabetic wound healing. Mater Sci Eng C. 2021;118:111385. Copyright 2021, with permission from Elsevier. (B) Synthesis and potential wound healing application of PABC hydrogel: Main components of PABC hydrogel including PEGDA, ALG and BGN; Reproduced from Li Y, Xu T, Tu Z, et al. Bioactive antibacterial silica-based nanocomposites hydrogel scaffolds with high angiogenesis for promoting diabeticwound healing and skin repair. Theranostics. 2020;10(11):4929–4943. Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).

Figure 4

Four kinds of natural bioactive ingredients based antibacterial hydrogel. (A) Mechanism of EGCG promoting wound healing; Reproduced from Zhao X, Pei D, Yang Y, et al. Green tea derivative driven smart hydrogels with desired functions for chronic diabetic wound treatment. Adv Funct Mater. 2021;31(18):2009442. Copyright 2021, John Wiley and sons. (B) Several antimicrobial pathways of EPL; Reproduced from Wang L, Zhang C, Zhang J, et al. Epsilon-poly-L-lysine: recent advances in biomanufacturing and applications. Front Bioeng Biotechnol.2021;9:748976. Copyright © 2021 Wang, Zhang, Zhang, Rao, Xu, Mao and Chen. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY). (C) Composition and action mode of the Gelma-dopa-amp-Ceons dressing; Reproduced from Cheng H, Shi Z, Yue K, et al. Sprayable hydrogel dressing accelerates wound healing with combined reactive oxygen species-scavenging and antibacterial abilities. Acta Biomater. 2021;124:219–232. Copyright 2021, with permission from Elsevier. (D) Structure of TA@bilayer hydrogel and its interaction with wound; Reproduced from Li Y, Fu R, Zhu C, Fan D. An antibacterial bilayer hydrogel modified by tannic acid with oxidation resistance and adhesiveness to accelerate woundrepair. Colloids Surf B. 2021;205:111869. Copyright 2021, with permission from Elsevier.

Figure 5

Digital image of E. coli (A) and S. aureus (C) clones on an AGAR plate after exposure; reproduced from Xu Z, Xu Z, Feng X, Xu D, Liang J, Xu H. Recent advances in the biotechnological production of microbial poly(ɛ-L-lysine) and understanding of its biosynthetic mechanism. Appl Microbiol Biotechnol. 2016;100(15):6619–6630. Copyright 2016, Springer Nature. Red circles indicate bacterial clones killed by hydrogel. In the presence of blank LB medium, G-PAGL-0, G-PAGL-I, G-PAGL-II, G-PAGL-III and G-PAGL-IV, the growth curves of (B) Escherichia coli and (D) Staphylococcus aureus varied with culture time.