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 inInternational journal of molecular sciences Vol. 23; no. 14; p. 7930
Main Authors Mieczkowski, Mateusz, Mrozikiewicz-Rakowska, Beata, Kowara, Michał, Kleibert, Marcin, Czupryniak, Leszek
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 19.07.2022
MDPI
Subjects
Diabetes
Diabetic retinopathy
Endothelium
Enzymes
Free radicals
Hyperglycemia
Kinases
Mortality
Nitric oxide
Pathogenesis
Patients
Review
Smooth muscle
Wound healing
Online AccessGet full text
ISSN1422-0067
1661-6596
1422-0067
DOI10.3390/ijms23147930

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Abstract 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).
AbstractList 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).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).
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).
Author Mrozikiewicz-Rakowska, Beata
Kleibert, Marcin
Mieczkowski, Mateusz
Kowara, Michał
Czupryniak, Leszek
AuthorAffiliation 2 Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland; michal.kowara@wum.edu.pl
1 Department of Diabetology and Internal Diseases, Medical University of Warsaw, 02-097 Warsaw, Poland; mateusz.mieczkowski@gmail.com (M.M.); marcin.kleibert@gmail.com (M.K.); leszek.czupryniak@wum.edu.pl (L.C.)
AuthorAffiliation_xml – name: 1 Department of Diabetology and Internal Diseases, Medical University of Warsaw, 02-097 Warsaw, Poland; mateusz.mieczkowski@gmail.com (M.M.); marcin.kleibert@gmail.com (M.K.); leszek.czupryniak@wum.edu.pl (L.C.)
– name: 2 Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland; michal.kowara@wum.edu.pl
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  surname: Mieczkowski
  fullname: Mieczkowski, Mateusz
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  orcidid: 0000-0002-1160-9204
  surname: Mrozikiewicz-Rakowska
  fullname: Mrozikiewicz-Rakowska, Beata
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  givenname: Michał
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  surname: Kowara
  fullname: Kowara, Michał
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  orcidid: 0000-0003-1562-8450
  surname: Kleibert
  fullname: Kleibert, Marcin
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  surname: Czupryniak
  fullname: Czupryniak, Leszek
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Snippet Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and...
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StartPage 7930
SubjectTerms Diabetes
Diabetic retinopathy
Endothelium
Enzymes
Free radicals
Hyperglycemia
Kinases
Mortality
Nitric oxide
Pathogenesis
Patients
Review
Smooth muscle
Wound healing
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Title The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model
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