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Review | Open Access

The role of glucose metabolism in wound healing: an overview

Tao Zhang1,‡, Youjing Yang2,‡, Junyu Jiang1, Wenyu Du1, Guangbin Huang1( ), Dingyuan Du1 ( ), Shasha Tao1,2 ( )
Department of Trauma Surgery, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, No. 1, Jiangkang Road, Yuzhong District, 400014, Chongqing, China
Chongqing Key Laboratory of Emergency Medicine, Chongqing Emergency Medical Center, Chongqing University Central Hospital, No. 1, Jiangkang Road, Yuzhong District, 400014, Chongqing, China

‡Tao Zhang and Youjing Yang contributed equally to this work

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Highlights

• Wound healing necessitates dynamic glucose metabolism shifts: glycolysis fuels early migration; oxidative phosphorylation drives later matrix synthesis. Chronic wounds exhibit metabolic dysfunction, suggesting “spatiotemporal regulation” as a therapy.

• Macrophage polarization (M1/M2) and glucose metabolism are interconnected. AMPK/STAT6 dysregulation in diabetic wounds impairs immune homeostasis, addressable via metabolic reprogramming.

• Enzymes (HK2/PFKFB3) and metabolites (lactate) exhibit dual therapeutic roles, promoting repair but potentially causing scar hyperplasia/inhibiting MMPs. Stage-specific interventions (e.g. PFKFB3 inhibition) and nanodelivery systems hold promise.

• Diabetic wounds display mitochondrial dysfunction (imbalanced dynamics, ROS), hindering healing. Mitochondrial transplantation or antioxidants (SkQ1) can restore metabolism and promote repair.

• Multi-pathway synergistic interventions, including traditional medicine and responsive materials, offer a comprehensive metabolic-immune-microenvironment approach for diabetic foot ulcers.

Abstract

Glucose metabolism is the core process by which cells obtain energy, providing adenosine triphosphate and metabolic intermediates through glycolysis and the tricarboxylic acid cycle and supporting cell proliferation, migration, and functional maintenance. It not only fuels cells but also cranks out nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway. This NADPH is crucial for fending off oxidative stress, keeping immune responses in check, and playing a role in cell signaling. During the process of wound healing, glucose metabolism plays a crucial role in each stage. In the early stage, cells rely on glycolysis to generate energy for proliferation and migration; during the inflammatory phase, immune cells generate reactive oxygen species through glucose metabolism to eliminate pathogens; and during the proliferation and remodeling phase, glucose metabolism supports the generation of the extracellular matrix and tissue repair. However, in chronic wounds, abnormal glucose metabolism increases oxidative stress and inflammatory responses, significantly delaying wound healing. Understanding how abnormal glucose metabolism affects the wound microenvironment and cell function can help researchers develop new therapeutic strategies. Therefore, this review breaks down how glucose metabolism works at each stage of wound healing. We are highlighting its potential as something we can target therapeutically, and hoping to spark some fresh ideas and avenues for research and clinical use down the road.

References

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Burns & Trauma
Article number: tkaf053

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Cite this article:
Zhang T, Yang Y, Jiang J, et al. The role of glucose metabolism in wound healing: an overview. Burns & Trauma, 2025, 13(9): tkaf053. https://doi.org/10.1093/burnst/tkaf053

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Received: 03 October 2024
Revised: 28 July 2025
Accepted: 30 July 2025
Published: 31 July 2025
© The Author(s) 2025. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.