Thou shall not heal: Overcoming the non-healing behaviour of diabetic foot ulcers by engineering the inflammatory microenvironment

Michael G Monaghan; Rajiv Borah; Charlotte Thomsen; Shane Browne

doi:10.1016/j.addr.2023.115120

Thou shall not heal: Overcoming the non-healing behaviour of diabetic foot ulcers by engineering the inflammatory microenvironment

Adv Drug Deliv Rev. 2023 Dec:203:115120. doi: 10.1016/j.addr.2023.115120. Epub 2023 Oct 25.

Authors

Michael G Monaghan¹, Rajiv Borah², Charlotte Thomsen³, Shane Browne⁴

Affiliations

¹ Department of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and BioEngineering Research (AMBER), Centre at Trinity College Dublin and the Royal College of Surgeons in Ireland, Dublin 2, Ireland; CÚRAM, Centre for Research in Medical Devices, National University of Ireland, H91 W2TY Galway, Ireland; Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland.
² Department of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland; Advanced Materials and BioEngineering Research (AMBER), Centre at Trinity College Dublin and the Royal College of Surgeons in Ireland, Dublin 2, Ireland; Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland.
³ Department of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland; Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
⁴ CÚRAM, Centre for Research in Medical Devices, National University of Ireland, H91 W2TY Galway, Ireland; Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin 2, Ireland; Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland. Electronic address: [email protected].

PMID: 37884128
DOI: 10.1016/j.addr.2023.115120

Abstract

Diabetic foot ulcers (DFUs) are a devastating complication for diabetic patients that have debilitating effects and can ultimately lead to limb amputation. Healthy wounds progress through the phases of healing leading to tissue regeneration and restoration of the barrier function of the skin. In contrast, in diabetic patients dysregulation of these phases leads to chronic, non-healing wounds. In particular, unresolved inflammation in the DFU microenvironment has been identified as a key facet of chronic wounds in hyperglyceamic patients, as DFUs fail to progress beyond the inflammatory phase and towards resolution. Thus, control over and modulation of the inflammatory response is a promising therapeutic avenue for DFU treatment. This review discusses the current state-of-the art regarding control of the inflammatory response in the DFU microenvironment, with a specific focus on the development of biomaterials-based delivery strategies and their cargos to direct tissue regeneration in the DFU microenvironment.

Keywords: Chronic wounds; Diabetic foot ulcers (DFU); Dressings; Drug delivery; Immunometabolism; Wound management.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus*
Diabetic Foot* / complications
Diabetic Foot* / drug therapy
Humans
Inflammation
Skin
Wound Healing