Food-Derived Tripeptide-Copper Self-Healing Hydrogel for Infected Wound Healing

Abstract

The field of infected wound management continues to face challenges, and traditional methods used to cope with wounds include debridement, gauze coverage, medication, and others. Currently, synthetic and natural biomaterials are readily available today, enabling the creation of new wound dressings that substantially enhance wound healing. Considerable attention is being paid to hydrogels based on natural materials, which have good biocompatibility and degradability properties, while exhibiting higher similarity to natural extracellular matrix as compared to synthetic materials. In this study, we extracted the active ingredients of oxidized konjac glucomannan (OKGM) and fresh egg white (EW) from 2 foods, konjac, and egg, respectively, and formed a self-repairing hydrogel based on the cross-linking of a Schiff base. Subsequently, a natural active peptide, glycyl-l-histidyl-l-lysine-Cu (GHK-Cu), was loaded, and an all-natural composite hydrogel dressing, EW/OKGM@GHK-Cu (GEK), was developed. The GEK hydrogel, exhibiting both antibacterial and anti-inflammatory properties, plays a hemostatic role by adhering to tissues and promoting neovascularization and serves as an optimal dressing for skin regeneration. Taken together, GEK hydrogel dressings derived from natural food sources therefore constitute an efficient and cost-effective strategy for managing infected wound healing and have significant potential for clinical application and transformation.

Fig. 1.

Schematic illustration of GEK hydrogel used in the repair of infected skin wounds.

Fig. 2.

Characterization of hydrogels. (A) Formation of GEK hydrogel by mixing EW and OKGM loaded with GHK-Cu. (B) SEM image. Scale bar, 200 μm. (C) Macroscopic injectivity of GEK hydrogel. (D) Shear-thinning properties. (E) Dynamic rheology test. (F) Strain scanning test of GEK hydrogel. (G) Swelling properties.

Fig. 3.

Cell biocompatibility. (A) Live/dead staining images of HUVEC and HACAT cocultured with hydrogel for 24 h. Scale bar, 100 μm. Quantitative analysis of the viability of (B) HUVEC and (C) HACAT.

Fig. 4.

Tubular formation experiment and scratch experiment. (A) Formation of HUVEC tubes in different hydrogel treatment groups. (B) HUVEC migration in different hydrogel treatment groups. (C) Relative tube length of HUVEC. (D) Migration rate of HUVEC. Scale bar, 100 μm.

Fig. 5.

Antibacterial properties. (A) Antibacterial properties of each hydrogel group were tested using a bacterial coating. (B) SEM images of bacteria under hydrogel intervention. Scale bar, 1 μm. Quantitative analysis of the antimicrobial effect of hydrogels against (C) E. coli and (D) S. aureus.

Fig. 6.

Wound healing and histological analyses. (A) Representative wounds. Scale bar, 5 mm. (B) H&E staining. Scale bar, 1 mm. Quantitative analysis of (C) wound healing and (D) tissue width.

Fig. 7.

Analysis of collagen deposition and proinflammatory factors in wounds. (A) Collagen, (B) TNF-α, and (C) IL-6 staining. (D to F) Collagen deposition and relative expression of IL-6 and TNF-α. Scale bar, 50 μm.

Fig. 8.

Immunofluorescent staining. (A) Fluorescent staining for neovascularization (α-SMA and CD31). Scale bar, 50 μm. (B) Relative vessel density.