2014
DOI: 10.1371/journal.pone.0109848
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A Novel Model of Chronic Wounds: Importance of Redox Imbalance and Biofilm-Forming Bacteria for Establishment of Chronicity

Abstract: Chronic wounds have a large impact on health, affecting ∼6.5 M people and costing ∼$25B/year in the US alone [1]. We previously discovered that a genetically modified mouse model displays impaired healing similar to problematic wounds in humans and that sometimes the wounds become chronic. Here we show how and why these impaired wounds become chronic, describe a way whereby we can drive impaired wounds to chronicity at will and propose that the same processes are involved in chronic wound development in humans… Show more

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Cited by 79 publications
(66 citation statements)
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References 90 publications
(101 reference statements)
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“…14 We have previously shown that TNFSF14/ LIGHT -/-mice display marked abnormalities in wound healing processes, including increased inflammation, oxidative and nitrosative stress, excessive coagulation and fibrin cuffs, vascular defects, and abnormal ECM deposition. 5,16 Furthermore, we also showed that the basement membrane of the blood vessels was not continuous, the microvessels had very few associated a-smooth muscle actin-expressing periendothelial cells, and contained significant intravascular coagulation, 16 resulting in immature/ defective vessels. Moreover, we have recently shown that in these mice with impaired healing, platelets have enhanced aggregation as well as shorter bleeding time.…”
Section: Introductionmentioning
confidence: 79%
See 1 more Smart Citation
“…14 We have previously shown that TNFSF14/ LIGHT -/-mice display marked abnormalities in wound healing processes, including increased inflammation, oxidative and nitrosative stress, excessive coagulation and fibrin cuffs, vascular defects, and abnormal ECM deposition. 5,16 Furthermore, we also showed that the basement membrane of the blood vessels was not continuous, the microvessels had very few associated a-smooth muscle actin-expressing periendothelial cells, and contained significant intravascular coagulation, 16 resulting in immature/ defective vessels. Moreover, we have recently shown that in these mice with impaired healing, platelets have enhanced aggregation as well as shorter bleeding time.…”
Section: Introductionmentioning
confidence: 79%
“…[2][3][4] Prediction of healing outcomes remains elusive due to the lack of understanding of the mechanisms involved in the etiology of impaired and chronic wounds, and often the coexisting morbidities. Furthermore, although a murine model for chronic wounds has been developed recently, 5,6 mechanistic studies are still lacking, thereby hindering the advancement in the development of diagnostics and therapeutics to treat these wounds. [7][8][9] Tissue injury causes the disruption of blood vessels and extravasation of blood constituents.…”
Section: Introductionmentioning
confidence: 99%
“…The importance of oxygen as a key mediator promoting wound healing has been addressed in several review articles [7][8][9][10]. Moreover, as a product of anaerobic metabolism, the accumulation of lactic acid causes additional toxicity in hypoxic tissues [11][12].…”
Section: Introductionmentioning
confidence: 99%
“…Ultimately this repetitive cycle overloads endogenous antioxidant machinery, resulting in elevated oxidative stress and a profoundly proinflammatory and tissue-destructive state, with damage inflicted to host cell proteins, lipids, and DNA (25,(143)(144)(145)(146)(147)(148)(149). Indeed, the first truly chronic wound model in the mouse hinges on locally elevating oxidative stress at the wound site, demonstrating the devastating potential of dysregulation of oxidative balance (150,151).…”
Section: Evidence For the Involvement Of Myeloid Cells In Aberrant Womentioning
confidence: 99%