Protocol to Create Chronic Wounds in Diabetic Mice

Kim, Jane Hannah; Martins‐Green, Manuela

doi:10.3791/57656

Cited by 16 publications

(22 citation statements)

References 1 publication

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“…Kim et al clarify that although various diabetes models display sex differences, no such differences were noted in their induction of chronic wounds using antioxidant enzyme inhibitors (AEIs). 32 In this research, the two groups treated with the antioxidant enzyme inhibitors appear to be arrested in the inflammatory stage on day 10 and had not healed by day 28. Wound healing occurs via a series of four overlapping stages: hemostasis, inflammation, proliferation, and remodeling.…”

Section: Discussionmentioning

confidence: 72%

Low mortality oxidative stress murine chronic wound model

Endo

Karvar

Sensharma

et al. 2020

BMJ Open Diab Res Care

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IntroductionInvestigators have struggled to produce a reliable chronic wound model. Recent progress with antioxidant enzyme inhibitors shows promise, but mortality rates are high. We modified the dosage and administration of an antioxidant enzyme inhibitor regimen to reduce mortality while inducing a chronic wound environment.Research design and methodsTo chemically induce a chronic wound environment, we applied modified doses of catalase (3-amino-1,2,4-triazole; intraperitoneal 0.5 g/kg) and glutathione peroxidase (mercaptosuccinic acid; topical 300 mg/kg) inhibitors to the dorsal wounds of 11-week-old db/db mice. A cohort of these mice was treated with a collagen-glycosaminoglycan scaffold. Both groups were compared with Diabetic control mice.ResultsThis study successfully induced a chronic wound in 11-week-old db/db mice, with no animal deaths. The antioxidant enzyme treated groups showed delayed wound contraction and significantly higher levels of inflammatory tissue, collagen deposition, cellular proliferation and leukocyte infiltration than the Diabetic control group. Angiogenesis was significantly higher in the antioxidant enzyme treated groups, but the vessels were immature and friable. Scaffold engraftment was poor but appeared to promote blood vessel maturation.ConclusionsOverall, the two in vivo groups treated with the antioxidant enzyme inhibitors appeared to be arrested in the inflammatory stage of wound healing, while the Diabetic control group progressed to the maturation phase and ultimately remodeling. This model may be instrumental for the development of new wound therapeutics.

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Section: Discussionmentioning

confidence: 72%

Low mortality oxidative stress murine chronic wound model

Endo

Karvar

Sensharma

et al. 2020

BMJ Open Diab Res Care

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“…All experiments were completed in accordance and compliance with federal regulations and University of California policy and all procedures have been approved by the University of California, Riverside Institutional Animal Care and Use Committee (IACUC). The detailed description of how to obtain chronic wounds in db/db −/− mice has been previously published by us (Dhall et al, 2014;Kim and Martins-Green, 2019). Briefly, db/db −/− mice were bred in house from B6.BKS(D)-Lepr db /J heterozygotes catalog #000697 from the Jackson Laboratories.…”

Section: Chronic Wound Modelmentioning

confidence: 99%

High Levels of Oxidative Stress Create a Microenvironment That Significantly Decreases the Diversity of the Microbiota in Diabetic Chronic Wounds and Promotes Biofilm Formation

Kim

Ruegger

Lebig

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Because chronic wounds usually occur in people affected by diabetes, ischemia, and mechanical pressure [ 8 , 65 ], these conditions are generally induced in animals, prior to the generation of an acute wound [ 66 , 67 , 68 , 69 ].…”

Section: Animal Models Of Wound Healingmentioning

confidence: 99%

“…Obvious differences in the anatomy and physiology of the skin in different species justify the use of multiple models, as no single one can reliably reproduce the clinical situation [61,62], and, more importantly, the comorbidities that are often responsible for chronic wounds [63,64]. Because chronic wounds usually occur in people affected by diabetes, ischemia, and mechanical pressure [8,65], these conditions are generally induced in animals, prior to the generation of an acute wound [66][67][68][69].…”

Section: Animal Models Of Wound Healingmentioning

confidence: 99%

Immune Cell Therapies to Improve Regeneration and Revascularization of Non-Healing Wounds

Groppa

Colliva

Vuerich

et al. 2020

IJMS

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With the increased prevalence of chronic diseases, non-healing wounds place a significant burden on the health system and the quality of life of affected patients. Non-healing wounds are full-thickness skin lesions that persist for months or years. While several factors contribute to their pathogenesis, all non-healing wounds consistently demonstrate inadequate vascularization, resulting in the poor supply of oxygen, nutrients, and growth factors at the level of the lesion. Most existing therapies rely on the use of dermal substitutes, which help the re-epithelialization of the lesion by mimicking a pro-regenerative extracellular matrix. However, in most patients, this approach is not efficient, as non-healing wounds principally affect individuals afflicted with vascular disorders, such as peripheral artery disease and/or diabetes. Over the last 25 years, innovative therapies have been proposed with the aim of fostering the regenerative potential of multiple immune cell types. This can be achieved by promoting cell mobilization into the circulation, their recruitment to the wound site, modulation of their local activity, or their direct injection into the wound. In this review, we summarize preclinical and clinical studies that have explored the potential of various populations of immune cells to promote skin regeneration in non-healing wounds and critically discuss the current limitations that prevent the adoption of these therapies in the clinics.

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Protocol to Create Chronic Wounds in Diabetic Mice

Cited by 16 publications

References 1 publication

Low mortality oxidative stress murine chronic wound model

Low mortality oxidative stress murine chronic wound model

High Levels of Oxidative Stress Create a Microenvironment That Significantly Decreases the Diversity of the Microbiota in Diabetic Chronic Wounds and Promotes Biofilm Formation

Immune Cell Therapies to Improve Regeneration and Revascularization of Non-Healing Wounds

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