Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
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The complex interactions that characterize acute wound healing have stymied the development of effective therapeutic modalities. The use of computational models holds the promise to improve our basic approach to understanding the process. By modifying an existing ordinary differential equation model of systemic inflammation to simulate local wound healing, we expect to improve the understanding of the underlying complexities of wound healing and thus allow for the development of novel, targeted therapeutic strategies. ⋯ Using these modifications we are able to simulate impaired wound healing in hypoxic wounds with varying levels of contamination. Possible therapeutic targets, such as fibroblast death rate and rate of fibroblast recruitment, have been identified by computational analysis. This model is a step toward constructing an integrative systems biology model of human wound healing.
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Personalized medicine is a major goal for the future of healthcare, and we suggest that computational simulations are necessary in order to achieve it. Inflammatory diseases, both acute and chronic, represent an area in which personalized medicine is especially needed, given the high level of individual variability that characterizes these diseases. ⋯ Since they include both circulating and tissue-level inflammatory mediators, these simulations transcend typical cytokine networks by associating inflammatory processes with tissue/organ damage via tissue damage/dysfunction. We suggest that computational simulations are the cornerstone of Translational Systems Biology approaches for inflammatory diseases.
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The introduction of mTOR-inhibitors in transplantation surgery has been associated with an increase in wound complications. We have previously reported a massive negative effect of everolimus on anastomotic strength in rat intestine at 7 days postoperatively. Because it is clinically important to know if this effect persists and occurs generally, repair in both intestine and abdominal wall has been investigated over a period of 4 weeks. ⋯ Loss of strength was accompanied by a decrease in hydroxyproline content after 7 days. Thus, the negative effect of everolimus on wound repair persists for at least 4 weeks after operation in this rodent model. This protracted effect may have clinical consequences and cause surgical morbidity.
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An in vitro efficacy study using newly developed artificial wound eschar (AWE) substrate was conducted for assessing enzyme dose response. The AWE substrate is prepared by the enzymatic conversion of fibrinogen to fibrin in the presence of collagen, fibrin, and elastin to form an insoluble planar matrix. AWE substrate was placed on Franz Diffusion Cells for continuously monitoring the debridement progress. ⋯ Using the histological measurement results (wound depth score) a dose response that correlated to the in vitro assessment was found. Granulation tissue maturity and reepithelialization displayed correlation with the enzyme dose. Results indicate that AWE substrate can be used to predict debridement efficacy in vitro when correlation to the in vivo assessment is achieved.
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Randomized Controlled Trial Multicenter Study
A multicenter clinical trial of recombinant human GM-CSF hydrogel for the treatment of deep second-degree burns.
Wound healing is a complex and dynamic biological process. The efficacy and safety of a recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) hydrogel to promote deep-second-degree burn wound healing is evaluated in this study. In this multicenter, randomized, double-blind, and placebo-controlled clinical trial, 90 patients with deep second-degree burns were randomly assigned into two groups. ⋯ A statistically significant difference was noted at each time point (p<0.01). No side effects were observed. These results suggest that rhGM-CSF hydrogel can significantly accelerate deep second-degree burn wound healing and is considered to be safe.