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Advances in diabetic wound healing: from pathophysiology to emerging therapies

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Diabetic wounds (DWs), particularly those affecting the lower extremities, represent a significant clinical challenge due to their chronic nature and high risk of complications, including infection and amputation. Despite advances in diabetes management, conventional wound care strategies often fail to achieve satisfactory healing outcomes, largely due to the complex pathophysiology of DWs, are involving impaired angiogenesis, chronic inflammation, and compromised immune responses. The data on the conventional and emerging therapies used in the management of DWs were searched using PubMed, Scopus, and Web of Science databases to locate literature published. Studies have shown that conventional wound care interventions like debridement, dressing, and infection control mostly provide symptomatic treatment without eliminating underlying cellular and molecular diabetic wound pathophysiology. Recent years have witnessed the emergence of novel therapeutic approaches, including stem cell therapy, gene therapy, nanotechnology-based interventions, and tissue engineering. These strategies improve angiogenesis, alter the polarization of macrophages, and stimulate tissue repair, which can offer new hope for enhancing wound healing in diabetic patients. This review synthesizes current literature on the pathophysiology of diabetic wound healing, evaluates the limitations of traditional therapies, and provides a comprehensive overview of cutting-edge treatments that holds an effective diabetic wound management.

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Abbreviations

DWs:

Diabetic wounds

DFUs:

Diabetic foot ulcers

AGEs:

Advanced glycation end products

ROS:

Reactive oxygen species

NO:

Nitric oxide

TNF:

Tumor necrosis factor

IL:

Interleukin

VEGF:

Vascular endothelial growth factor

PDGF:

Platelet-derived growth factor

EGF:

Epidermal growth factor

KGF:

Keratinocyte growth factor

TGF-1:

Transforming growth factor beta 1

IGF-1:

Insulin growth factor-1

FGF:

Fibroblast growth factor

ECM:

Extracellular matrix tissue

MSCs:

Mesenchymal stem cells

ESCs:

Embryonic stem cells

EBB:

Extrusion-based bioprinting

ILM:

Insulin-loaded micelles

MiRNAs:

Micro RNA

CRP:

C-Reactive protein

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Acknowledgements

The authors acknowledge the JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSS AHER), Mysuru, India, for providing the necessary research facilities, infrastructure, academic support, and JSSAHER Research Grant (JSSAHER/REG/RES/URG/54/2023-24).

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Authors and Affiliations

  1. Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Tamil Nadu, 643001, India

    Swati Swagatika Swain, Veera Venkata Satyanarayana Reddy Karri, Kuppuswamy Gowthamarajan & Manimaran Bhaskaran

  2. The School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom

    Md Ekhtiar Uddin

  3. Department of Pharmacology, Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Petaling Jaya, Selangor, Malaysia

    Vetriselvan Subramaniyan

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  1. Swati Swagatika Swain
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Contributions

Swati Swagatika Swain: Wring original draft. Data curation, Formal analysis. Veera Venkata Satyanarayana Reddy Karri: Conceptualization, Writing, Reviewing, and Editing, Supervision, Md Ekhtiar Uddin: Writing, Reviewing, and Editing, Kuppuswamy Gowthamarajan: Reviewing and Editing. Manimaran B: Reviewing and Editing. Vetriselvan Subramaniyan: Reviewing and Editing.

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Correspondence to Veera Venkata Satyanarayana Reddy Karri.

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Communicated by Salvatore Corrao, M.D.

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Swain, S.S., Karri, V.V.S.R., Uddin, M.E. et al. Advances in diabetic wound healing: from pathophysiology to emerging therapies. Acta Diabetol (2025). https://doi.org/10.1007/s00592-025-02629-6

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