The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model

Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects...

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Published in:International journal of molecular sciences 2022-07, Vol.23 (14), p.7930
Main Authors: Mieczkowski, Mateusz, Mrozikiewicz-Rakowska, Beata, Kowara, Michał, Kleibert, Marcin, Czupryniak, Leszek
Format: Article
Language:English
Subjects:
Aging
Amputation
animal model
Animal models
Arteriosclerosis
Atherosclerosis
chronic wound
Clinical trials
Diabetes
Diabetes mellitus
diabetic foot syndrome
Diabetic retinopathy
Endothelium
Enzymes
Etiology
Free radicals
Hyperglycemia
Kinases
Microvasculature
molecular mechanism
Mortality
Nitric oxide
Pathogenesis
Patients
Review
Sepsis
Smooth muscle
Wound healing
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Summary:Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects in whom the healing process is particularly prolonged regardless of its initial etiology. Circulatory dysfunction, both at the microvascular and macrovascular levels, is a leading factor in delaying or precluding wound healing in diabetes. The prolonged period of wound healing increases the risk of complications such as the development of infection, including sepsis and even amputation. Currently, many substances applied topically or systemically are supposed to accelerate the process of wound regeneration and finally wound closure. The role of clinical trials and preclinical studies, including research based on animal models, is to create safe medicinal products and ensure the fastest possible healing. To achieve this goal and minimize the wide-ranging burdens associated with conducting clinical trials, a correct animal model is needed to replicate the wound conditions in patients with diabetes as closely as possible. The aim of the paper is to summarize the most important molecular pathways which are impaired in the hyperglycemic state in the context of designing an animal model of diabetic chronic wounds. The authors focus on research optimization, including economic aspects and model reproducibility, as well as the ethical dimension of minimizing the suffering of research subjects according to the 3 Rs principle (Replacement, Reduction, Refinement).
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23147930