A Versatile Glycopeptide Hydrogel Promotes Chronic Refractory Wound Healing Through Bacterial Elimination, Sustained Oxygenation, Immunoregulation, and Neovascularization

Abstract

Chronic refractory wounds have become a severe threat to public health and are characterized by repeated bacterial infections, persistent hypoxia, abnormal immune regulation, and obstruction of angiogenesis. However, current treatment strategies usually perform only one or two therapeutic functions and cannot satisfy the dynamic and complex demands of chronic wound healing. Herein, a versatile dynamic Schiff base and borate ester cross‐linked glycopeptide hydrogel is prepared from phenylboronic acid‐grafted ε‐polylysine (EPBA), epigallocatechin‐3‐gallate (EGCG), and oxidized alginate. Customized polydopamine‐coated honeycomb MnO2 nanoparticles loaded with herb‐derived salvianolic acid B (PHMS) are embedded into the hydrogel before gelation. Under the distinct acidic and oxidative microenvironment of chronic refractory wounds, the hydrogel gradually dissociates, and the released EPBA effectively eliminates bacteria, while the released EGCG and PHMS eradicates reactive oxygen and nitrogen species, promotes M2 polarization of macrophages, and continuously generates oxygen. Then PHMS further disintegrates, and the released salvianolic acid B promotes angiogenesis through the PI3K/Akt pathway. The versatile glycopeptide hydrogel accelerates Staphylococcus aureus‐infected diabetic cutaneous wound repair in vivo and is a promising candidate dressing for chronic refractory wound healing.

Glucose Oxidase and Catalase-Loaded ZnS Nanozymes for Regulating the Local Microenvironment and Promoting Wound Healing in Diabetes

“…After 24 h, compared with the blank group (normal cell group without any sample), ZnS-GC and ZnS-GC (HCl) particle balls, the scratches of the remaining samples completely healed. This may be attributed to the catalytic cascade reaction of GOX and CAT in high glucose environment, which not only solved the hypoxic environment but also triggered the continuous release of Zn 2+ and H 2 S gas from ZnS to stimulate the rapid migration of two kinds of cells. , This phenomenon is consistent with the effect of ZnS-GC spheres on cell proliferation.…”

“…This may be attributed to the catalytic cascade reaction of GOX and CAT in high glucose environment, which not only solved the hypoxic environment but also triggered the continuous release of Zn 2+ and H 2 S gas from ZnS to stimulate the rapid migration of two kinds of cells. 42,43 This phenomenon is consistent with the effect of ZnS-GC spheres on cell proliferation. In addition, the high glucose environment and hypoxia at the wound site can damage the proliferation and migration of L929 and ECs cells, resulting in difficulty in wound healing.…”

Extracellular Matrix-Mimetic Intrinsic Versatile Coating Derived from Marine Adhesive Protein Promotes Diabetic Wound Healing through Regulating the Microenvironment

“…The impaired immune system is accompanied by repeated pathogenic bacterial infections in diabetic wounds, and the continuously secreted exudate creates a favorable environment for bacterial growth . LL37 has been proven to be an effective antibacterial peptide to combat harmful bacterial infection and regulate immune responses. , To design an intrinsically functional coating, we employed genetic engineering to fuse LL37 to the Sbp9 Δ protein (Figure a).…”

“…In general, wound healing is a well-orchestrated physiological and dynamic process, but in diabetic wounds, repair intermits at the inflammatory phase . The complicated wound microenvironment contributing to DFUs is outlined below: (1) the imbalance of the inflammatory response caused by excessive inflammatory cytokines and infiltrated immune cells . Especially, the inflammatory environment hindered the pro-inflammatory M1 macrophages switch to pro-healing M2 macrophages .…”

Programmed microalgae-gel promotes chronic wound healing in diabetes

“…The hydrogel is engineered to simultaneously match the mechanical and electrical signals of the skin while possessing oxidative capability activated by H 2 O 2 34 . Wu et al prepared a versatile dynamic Schiff base and borate ester cross-linked glycopeptide hydrogel that could continuously generate oxygen, promote M2 polarization of macrophages, and eliminate reactive oxygen and nitrogen species 35 . Zhang et al prepared an injectable hydrogel based on platelet-rich plasma and laponite that could accelerate wound healing by promoting macrophage polarization and angiogenesis in full-thickness skin 36 .…”