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Journal ArticleDOI

The role of matrix metalloproteinases in wound healing

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TLDR
Results from key studies suggest that neutrophil-derived matrix metalloproteinase 8 (MMP-8) is the predominant collagenase present in normal healing wounds, and that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic leg ulcers.
Abstract
The structure, classification, function, and regulation of matrix metalloproteinases in normal and abnormal wound healing is discussed. Results from key studies suggest that neutrophil-derived matrix metalloproteinase 8 (MMP-8) is the predominant collagenase present in normal healing wounds, and that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic leg ulcers. Excessive collagenolytic activity in these chronic wounds is possible because of the reduced levels of tissue inhibitor metalloproteinase 1 (TIMP-1). However, until recently, there have been no studies evaluating levels of matrix metalloproteinase or tissue inhibitors of metalloproteinase activity in chronic diabetic foot wounds. Improving basic knowledge and pharmaceutical intervention in this area ultimately may help clinicians identify and proactively intervene in an effort to prevent normal wounds from becoming chronic. This may prevent the high prevalence of morbidity associated with this significant health problem. (J Am Podiatr Med Assoc 92(1): 12-18, 2002)

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Citations
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Journal ArticleDOI

The molecular biology of chronic wounds and delayed healing in diabetes.

R. Blakytny, +1 more
- 01 Jun 2006 - 
TL;DR: A review of the work done at the molecular level on chronic diabetic ulcers, as well as considering changes seen in diabetes in general, both in humans and animal models that may in turn contribute to ulcer formation are examined.
Journal ArticleDOI

Bacterial load in relation to vacuum-assisted closure wound therapy: a prospective randomized trial.

TL;DR: A positive effect of vacuum‐assisted closure therapy on wound healing is shown, expressed as a significant reduction of wound surface area, however, this could not be explained by a significant quantitative reduction of the bacterial load.
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Mechanistic insight into diabetic wounds: Pathogenesis, molecular targets and treatment strategies to pace wound healing.

TL;DR: This review mainly focuses on the molecular cascades of cytokines (with growth factors) and erstwhile factors responsible for delayed wound healing, molecular targets and recent advancements in complete healing and its cure.
Journal ArticleDOI

Biofilms and chronic wound inflammation.

TL;DR: In contrast to the commonly accepted hypothesis of host-centred pathology, it is possible that surface bacteria, not host dysfunction, cause the chronicity and perpetual inflammation associated with chronic non-healing wounds.
Journal ArticleDOI

Proteases and Delayed Wound Healing.

TL;DR: It seems plausible that future research should aim to investigate the ways in which proteases may be targeted as an alternative therapeutic approach to wound management and to assess the benefits and draw-backs of utilizing wound fluids to assess wound progression in terms of proteolytic activity.
References
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Journal ArticleDOI

The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family.

TL;DR: Observations support the view that the cysteine-switch mechanism is applicable to all members of this gene family and offers the opportunity for multiple modes of physiological activation of these important enzymes.
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Proteolytic remodeling of extracellular matrix

TL;DR: Evidence is emerging that these enzymes also play an important regulatory role in matrix remodeling by catalyzing the processing of inactive matrix metalloproteinase and cytokine precursors.
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Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors.

TL;DR: The elevated levels of matrix metalloproteinase activity decreased significantly as healing occurs in chronic leg ulcers, which parallels the processes observed in normally healing acute wounds and supports the case for the addition of protease inhibitors in chronic wounds in conjunction with any treatments using growth factors.
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Wound Fluid from Chronic Leg Ulcers Contains Elevated Levels of Metalloproteinases MMP-2 and MMP-9

TL;DR: The results suggest that non-healing ulcers develop an environment containing high levels of activated metalloproteinases, which may result in chronic tissue turnover and failed wound closure.
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