Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
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Effect of hyperbaric oxygen on human skin cells in culture and in human dermal and skin equivalents.
A critical stage of cutaneous wound healing is the development and maturation of the epidermis. In the aged, and in certain pathologies, this repair process is compromised due to a variety of deficiencies, one of which is tissue oxygenation. Several phases of wound healing are dependent on adequate tissue oxygen levels, and hyperbaric oxygenation has been shown to transiently elevate these levels. ⋯ In contrast, hyperbaric treatment up to 3 atmospheres dramatically enhanced keratinocyte differentiation, and epidermopoiesis in the complete human skin equivalent. These results support the importance of hyperbaric oxygen therapy in wound healing, and should provide an insight into oxygen utilization during repair of peripheral human tissue. The results also show the utility of the human skin equivalent as a model for evaluation of parameters involved in wound healing.
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Comparative Study Clinical Trial
Dynamics of the matrix metalloproteinases MMP-1 and MMP-8 in acute open human dermal wounds.
Extracellular matrix degradation during dermal wound healing involves multiple levels of regulation by several enzymes of the matrix metalloproteinase family, their activators, and their inhibitors. This study tested the hypothesis that a temporal pattern of interstitial collagenase appearance occurs during normal dermal wound healing, with matrix metalloproteinase-8 originating from neutrophils appearing earlier than the fibroblast-derived matrix metalloproteinase-1. Open (6 mm) full-thickness dermal wounds, which were covered by transparent occlusive dressings, were made in healthy human volunteers (n = 20). ⋯ Tissue inhibitor of metalloproteinases-1 levels declined over time, whereas levels of matrix metalloproteinase-1/tissue inhibitor of metalloproteinase-1 complexes increased to a plateau on day 7. This study provides new evidence implicating matrix metalloproteinase-8 as a major collagenase in healing human dermal wounds. It also shows a temporal pattern in the appearance of the matrix metalloproteinases, tissue inhibitor of metalloproteinase-1, and matrix metalloproteinase-1/tissue inhibitor of metalloproteinases-1 complexes, suggesting that a tightly regulated pattern of expression of matrix metalloproteinases and their inhibitors is essential for normal wound healing in humans.
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Wound healing can be accelerated by removing necrotic tissue. Various methods of wound debridement have been developed, including enzymatic debridement. Recently potent proteolytic enzymes were isolated from the intestine of Euphausia superba (Antarctic krill) that might be useful for degrading necrotic tissue. ⋯ The debriding effect of krill enzymes at a concentration of >/= 3.0 casein units per ml was significantly better than saline control treatment (p < 0.05). The effect was dose dependent, and granulation tissue formation was enhanced. In conclusion, krill enzymes are effective in wound debridement, as measured in this animal model.
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Wound healing is the result of a dynamic balance between synthetic and degradative processes. After a burn, proteolytic activity increases at the wound site. Excised burn wounds and donor skin were examined from 20 pediatric burn patients, to determine which of two classes of neutral proteinases, serine or metalloproteinases, accounts for the majority of this proteolytic activity in these tissues; to examine messenger RNA expression of three of the principal enzymes and inhibitors of this class; and to measure enzymatic activity of two of these metalloproteinases. ⋯ By zymography, there was a significant increase in matrix metalloproteinase-2 (twofold to threefold) and matrix metalloproteinase-9 (20- to 30-fold) activity in burned versus unburned skin. We suggest that postburn there is an upregulation of some matrix metalloproteinases that exceeds the level of inhibitors with the net result of an increase in proteolysis in burned tissue. This increased proteolysis may play a role in wound repair and scar formation.
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An enzymatic debriding preparation was formulated with purified enzyme derived from a crude pineapple stem extract. The primary component of this preparation was the sulfhydryl protease ananain which represented >/=85% of the proteolytic activity. The remaining proteolytic activity in the preparation was contributed by a co-purifying homologous cysteine protease comosain. ⋯ Complete debridement of these wounds was accomplished within 4 to 5 days. Treatment of ischemic cutaneous ulcerations in this animal model with two commercially available enzyme-debriding agents provided little or no debridement of the necrotic tissue. In vitro, Vianain treatment of surgically debrided human tissue samples, obtained from patients with burn injury or cutaneous ulcers, showed that the protease preparation was effective in rapidly digesting these necrotic tissues.