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Review
. 2024 Sep 30:139:112713.
doi: 10.1016/j.intimp.2024.112713. Epub 2024 Jul 23.

Molecular immunological mechanisms of impaired wound healing in diabetic foot ulcers (DFU), current therapeutic strategies and future directions

Fatima Mohsin  1 , Sheza Javaid  2 , Mishal Tariq  3 , Muhammad Mustafa  4
Affiliations
Review

Molecular immunological mechanisms of impaired wound healing in diabetic foot ulcers (DFU), current therapeutic strategies and future directions

Fatima Mohsin et al. Int Immunopharmacol. .

Abstract

Diabetic foot ulcer (DFU) is a foremost cause of amputation in diabetic patients. Consequences of DFU include infections, decline in limb function, hospitalization, amputation, and in severe cases, death. Immune cells including macrophages, regulatory T cells, fibroblasts and other damage repair cells work in sync for effective healing and in establishment of a healthy skin barrier post-injury. Immune dysregulation during the healing of wounds can result in wound chronicity. Hyperglycemic conditions in diabetic patients influence the pathophysiology of wounds by disrupting the immune system as well as promoting neuropathy and ischemic conditions, making them difficult to heal. Chronic wound microenvironment is characterized by increased expression of matrix metalloproteinases, reactive oxygen species as well as pro-inflammatory cytokines, resulting in persistent inflammation and delayed healing. Novel treatment modalities including growth factor therapies, nano formulations, microRNA based treatments and skin grafting approaches have significantly augmented treatment efficiency, demonstrating creditable efficacy in clinical practices. Advancements in local treatments as well as invasive methodologies, for instance formulated wound dressings, stem cell applications and immunomodulatory therapies have been successful in targeting the complex pathophysiology of chronic wounds. This review focuses on elucidating the intricacies of emerging physical and non-physical therapeutic interventions, delving into the realm of advanced wound care and comprehensively summarizing efficacy of evidence-based therapies for DFU currently available.

Keywords: Chronic wounds; Diabetic foot ulcers; Immunomodulatory therapies; Nanotherapeutic approaches; Stem cell therapies; Wound dressing; Wound healing.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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