Zinc-based Polyoxometalate Nanozyme Functionalized Hydrogels for Optimizing the Hyperglycemic-Immune Microenvironment to Promote Diabetic Wound Regeneration

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2024 Oct 8

PMID 39380018

Authors

Chaoyu Pu

Yong Wang

Honglin Xiang

Jiangtao He

Qiyuan Sun

Yuan Yong

Lu Chen

Ke Jiang

Hanfeng Yang

Yuling Li

Affiliations

Soon will be listed here.

Abstract

Background: In diabetic wounds, hyperglycemia-induced cytotoxicity and impaired immune microenvironment plasticity directly hinder the wound healing process. Regulation of the hyperglycemic microenvironment and remodeling of the immune microenvironment are crucial.

Results: Here, we developed a nanozymatic functionalized regenerative microenvironmental regulator (AHAMA/CS-GOx@Zn-POM) for the effective repair of diabetic wounds. This novel construct integrated an aldehyde and methacrylic anhydride-modified hyaluronic acid hydrogel (AHAMA) and chitosan nanoparticles (CS NPs) encapsulating zinc-based polymetallic oxonate nanozyme (Zn-POM) and glucose oxidase (GOx), facilitating a sustained release of release of both enzymes. The GOx catalyzed glucose to gluconic acid and (H₂O₂), thereby alleviating the effects of the hyperglycemic microenvironment on wound healing. Zn-POM exhibited catalase and superoxide dismutase activities to scavenge reactive oxygen species and H₂O₂, a by-product of glucose degradation. Additionally, Zn-POM induced M1 macrophage reprogramming to the M2 phenotype by inhibiting the MAPK/IL-17 signaling diminishing pro-inflammatory cytokines, and upregulating the expression of anti-inflammatory mediators, thus remodeling the immune microenvironment and enhancing angiogenesis and collagen regeneration within wounds. In a rat diabetic wound model, the application of AHAMA/CS-GOx@Zn-POM enhanced neovascularization and collagen deposition, accelerating the wound healing process.

Conclusions: Therefore, the regenerative microenvironment regulator AHAMA/CS-GOx@Zn-POM can achieve the effective conversion of a pathological microenvironment to regenerative microenvironment through integrated control of the hyperglycemic-immune microenvironment, offering a novel strategy for the treatment of diabetic wounds.

References

Peng X, Li Y, Li T, Li Y, Deng Y, Xie X . Coacervate-Derived Hydrogel with Effective Water Repulsion and Robust Underwater Bioadhesion Promotes Wound Healing. Adv Sci (Weinh). 2022; 9(31):e2203890. PMC: 9631067. DOI: 10.1002/advs.202203890. View

Pi L, Yang L, Fang B, Meng X, Qian L . Exosomal microRNA-125a-3p from human adipose-derived mesenchymal stem cells promotes angiogenesis of wound healing through inhibiting PTEN. Mol Cell Biochem. 2021; 477(1):115-127. DOI: 10.1007/s11010-021-04251-w. View

Qi X, Cai E, Xiang Y, Zhang C, Ge X, Wang J . An Immunomodulatory Hydrogel by Hyperthermia-Assisted Self-Cascade Glucose Depletion and ROS Scavenging for Diabetic Foot Ulcer Wound Therapeutics. Adv Mater. 2023; 35(48):e2306632. DOI: 10.1002/adma.202306632. View

Kang H, Kumar S, DElia A, Dash B, Nanda V, Hsia H . Self-assembled elastin-like polypeptide fusion protein coacervates as competitive inhibitors of advanced glycation end-products enhance diabetic wound healing. J Control Release. 2021; 333:176-187. PMC: 10927318. DOI: 10.1016/j.jconrel.2021.03.032. View

Chen S, Zhu Y, Xu Q, Jiang Q, Chen D, Chen T . Photocatalytic glucose depletion and hydrogen generation for diabetic wound healing. Nat Commun. 2022; 13(1):5684. PMC: 9515190. DOI: 10.1038/s41467-022-33475-7. View

Ni D, Jiang D, Kutyreff C, Lai J, Yan Y, Barnhart T . Molybdenum-based nanoclusters act as antioxidants and ameliorate acute kidney injury in mice. Nat Commun. 2018; 9(1):5421. PMC: 6303396. DOI: 10.1038/s41467-018-07890-8. View

Nosrati H, Heydari M, Khodaei M . Cerium oxide nanoparticles: Synthesis methods and applications in wound healing. Mater Today Bio. 2023; 23:100823. PMC: 10622885. DOI: 10.1016/j.mtbio.2023.100823. View

Nethi S, Das S, Ranjan Patra C, Mukherjee S . Recent advances in inorganic nanomaterials for wound-healing applications. Biomater Sci. 2019; 7(7):2652-2674. DOI: 10.1039/c9bm00423h. View

Cui Q, Du H, Ma Y, Wang T, Zhu H, Zhu L . Matrine inhibits advanced glycation end products-induced macrophage M1 polarization by reducing DNMT3a/b-mediated DNA methylation of GPX1 promoter. Eur J Pharmacol. 2022; 926:175039. DOI: 10.1016/j.ejphar.2022.175039. View

10.

Boniakowski A, Kimball A, Jacobs B, Kunkel S, Gallagher K . Macrophage-Mediated Inflammation in Normal and Diabetic Wound Healing. J Immunol. 2017; 199(1):17-24. DOI: 10.4049/jimmunol.1700223. View

11.

Loo H, Goh B, Lee L, Chuah L . Application of chitosan-based nanoparticles in skin wound healing. Asian J Pharm Sci. 2022; 17(3):299-332. PMC: 9237591. DOI: 10.1016/j.ajps.2022.04.001. View

12.

Li S, Sengupta D, Chien S . Vascular tissue engineering: from in vitro to in situ. Wiley Interdiscip Rev Syst Biol Med. 2013; 6(1):61-76. DOI: 10.1002/wsbm.1246. View

13.

Huang S, Wu C, Chiu M, Wu C, Chang Y, Chen G . High glucose environment induces M1 macrophage polarization that impairs keratinocyte migration via TNF-α: An important mechanism to delay the diabetic wound healing. J Dermatol Sci. 2019; 96(3):159-167. DOI: 10.1016/j.jdermsci.2019.11.004. View

14.

Aitcheson S, Frentiu F, Hurn S, Edwards K, Murray R . Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds. Molecules. 2021; 26(16). PMC: 8398285. DOI: 10.3390/molecules26164917. View

15.

Liu J, Chen Z, Liu H, Qin S, Li M, Shi L . Nickel-Based Metal-Organic Frameworks Promote Diabetic Wound Healing via Scavenging Reactive Oxygen Species and Enhancing Angiogenesis. Small. 2023; 20(10):e2305076. DOI: 10.1002/smll.202305076. View

16.

Su J, Wei Q, Ma K, Wang Y, Hu W, Meng H . P-MSC-derived extracellular vesicles facilitate diabetic wound healing via miR-145-5p/ CDKN1A-mediated functional improvements of high glucose-induced senescent fibroblasts. Burns Trauma. 2023; 11:tkad010. PMC: 10583213. DOI: 10.1093/burnst/tkad010. View

17.

Xue B, Ge M, Fan K, Huang X, Yan X, Jiang W . Mitochondria-targeted nanozymes eliminate oxidative damage in retinal neovascularization disease. J Control Release. 2022; 350:271-283. DOI: 10.1016/j.jconrel.2022.08.026. View

18.

Qu A, Chen Q, Sun M, Xu L, Hao C, Xu C . Sensitive and Selective Dual-Mode Responses to Reactive Oxygen Species by Chiral Manganese Dioxide Nanoparticles for Antiaging Skin. Adv Mater. 2023; 36(5):e2308469. DOI: 10.1002/adma.202308469. View

19.

Wu X, Zhu H, Che J, Xu Y, Tan Q, Zhao Y . Stem cell niche-inspired microcarriers with ADSCs encapsulation for diabetic wound treatment. Bioact Mater. 2023; 26:159-168. PMC: 10008968. DOI: 10.1016/j.bioactmat.2023.02.031. View

20.

Zhang Y, Sheng R, Chen J, Wang H, Zhu Y, Cao Z . Silk Fibroin and Sericin Differentially Potentiate the Paracrine and Regenerative Functions of Stem Cells Through Multiomics Analysis. Adv Mater. 2023; 35(20):e2210517. DOI: 10.1002/adma.202210517. View