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Review
. 2022 Feb 17;8(2):127.
doi: 10.3390/gels8020127.

Functional Hydrogels for Treatment of Chronic Wounds

Ilayda Firlar  1   2 , Mine Altunbek  2 , Colleen McCarthy  2 , Murugan Ramalingam  3   4 , Gulden Camci-Unal  2   5
Affiliations
Review

Functional Hydrogels for Treatment of Chronic Wounds

Ilayda Firlar et al. Gels. .

Abstract

Chronic wounds severely affect 1-2% of the population in developed countries. It has been reported that nearly 6.5 million people in the United States suffer from at least one chronic wound in their lifetime. The treatment of chronic wounds is critical for maintaining the physical and mental well-being of patients and improving their quality of life. There are a host of methods for the treatment of chronic wounds, including debridement, hyperbaric oxygen therapy, ultrasound, and electromagnetic therapies, negative pressure wound therapy, skin grafts, and hydrogel dressings. Among these, hydrogel dressings represent a promising and viable choice because their tunable functional properties, such as biodegradability, adhesivity, and antimicrobial, anti-inflammatory, and pre-angiogenic bioactivities, can accelerate the healing of chronic wounds. This review summarizes the types of chronic wounds, phases of the healing process, and key therapeutic approaches. Hydrogel-based dressings are reviewed for their multifunctional properties and their advantages for the treatment of chronic wounds. Examples of commercially available hydrogel dressings are also provided to demonstrate their effectiveness over other types of wound dressings for chronic wound healing.

Keywords: chronic wounds; hydrogels; polymers; wound dressings; wound healing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Wound healing stages demonstrated on the three layers of human skin. There are four- tightly controlled stages of wound healing in the human body: (A) Hemostasis is the first stage and acts as the first response when blood vessels are damaged and blood leaks into the wound area; (B) Inflammation is the second phase and involves vasodilation which helps to prevent infection by triggering the formation of a blood clot and cleaning the wound site with leukocytes; (C) Proliferation is the tissue development phase of wound healing. Granulated tissue with an extracellular matrix (ECM) composed of new connective tissue and blood vessels is formed in the presence of an appropriate amount of moisture and oxygen; (D) Re-modeling is the last stage and is regulated by differentiated myofibroblasts. The ECM of the wounded tissue is reconstituted similar to normal tissue. Many of the newly produced capillaries regress and restore the vascular density of the wound to normal. Created with BioRender.com accessed on 13 November 2021.
Figure 2
Figure 2
Development of bioadhesive, antioxidant, and antimicrobial multifunctional chitosan-based hydrogels for wound dressings. (A) Schematic representation for modification of chitosan with gallic acid (CS-GA). (B) Demonstration for adhesion, stretching, and removal of CS-GA from the skin surface. (C) Adhesion strength comparison (Student’s t-test, **** p < 0.0001). and (D) ROS scavenging performance based on the amount of GA grafting (E) Antimicrobial activity of CS, GA, and CS with different GA contents (G1 < G2 < G3) against Escherichia coli (E. coli) and Staphylococcus aureus (S.A.). Reproduced with permission [58]. Copyright 2022 Elsevier.
Figure 3
Figure 3
(A) Schematic representation for a pH-responsive chitosan based-hydrogel targeted for diabetic foot ulcer treatment. A hybrid hydrogel (Gel) was constructed between N-carboxyethyl chitosan (N-chitosan), hyaluronic acid–aldehyde (HA-ALD), and adipic acid dihydrazide (ADH). Insulin was loaded into the polymer solution and reversible dynamic bonds were provided by acylhydrazone and imine bonds (Gel+In). pH responsive properties were achieved with acylhydrazone bonds. (B) pH-responsive release behavior of insulin for 14 days (C) Quantitative analysis of the number of inflammatory cells at 4 and 12 days after the operation (Tukey’s post-hoc analysis, * p < 0.05) (D) Quantitative analysis for wound area measured on days 0, 4, 8, and 12 (Tukey’s post-hoc analysis, * p < 0.05, ** p < 0.01, *** p < 0.001 compared with control group; # p < 0.05 compared with the hydrogel group) (E) Masson trichrome staining to show collagen deposition on days 4 and 12 after the application of Gel and Gel+In to full thickness foot skin wounds on diabetic rats (W: Wound area, N: Normal tissue). Reproduced with permission [128]. Copyright 2021 Elsevier.
Figure 4
Figure 4
(A) Schematic representation of the fabrication of a drug releasing hydrogel. Metformin hydrochloride (MH) and curcumin (Cur) incorporated in a copper-based hybrid composite hydrogel Cur/MH/HKUST-1@Gel for murine diabetic wound healing. (B) Representative wound closure images of diabetic mice treated with Cur, MH, HKUST-1, Gel, Cur/MH/HKUST-1, and Cur/MH/HKUST-1@Gel for 20 days. (C) H&E staining images exhibiting tissue granulation and (D) Immunofluorescence staining images of CD31 to show neovascularization in mice skin tissue upon treatment with different groups. Reproduced with permission [127]. Copyright 2022 Elsevier.
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