scholarly journals Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Christin von Müller ◽  
Fionnuala Bulman ◽  
Lysett Wagner ◽  
Daniel Rosenberger ◽  
Alessandra Marolda ◽  
...  
Keyword(s):  
Human Skin ◽  
Ex Vivo ◽  
Burn Wound ◽  
Local Immunity ◽  
Fungal Virulence ◽  
Opportunistic Fungi ◽  
Burn Wounds ◽  
Wound Model ◽  
Skin Explants ◽  
Bacteria And Fungi

AbstractBurn wounds are highly susceptible sites for colonization and infection by bacteria and fungi. Large wound surface, impaired local immunity, and broad-spectrum antibiotic therapy support growth of opportunistic fungi such as Candida albicans, which may lead to invasive candidiasis. Currently, it remains unknown whether depressed host defenses or fungal virulence drive the progression of burn wound candidiasis. Here we established an ex vivo burn wound model, where wounds were inflicted by applying preheated soldering iron to human skin explants, resulting in highly reproducible deep second-degree burn wounds. Eschar removal by debridement allowed for deeper C. albicans penetration into the burned tissue associated with prominent filamentation. Active migration of resident tissue neutrophils towards the damaged tissue and release of pro-inflammatory cytokine IL-1β accompanied the burn. The neutrophil recruitment was further increased upon supplementation of the model with fresh immune cells. Wound area and depth decreased over time, indicating healing of the damaged tissue. Importantly, prominent neutrophil presence at the infected site correlated to the limited penetration of C. albicans into the burned tissue. Altogether, we established a reproducible burn wound model of candidiasis using ex vivo human skin explants, where immune responses actively control the progression of infection and promote tissue healing.

scholarly journals Modelling early thermal injury using an ex vivo human skin model of contact burns

2020 ◽  
Author(s):  
Aiping Liu ◽  
Edgar Ocotl ◽  
Aos Karim ◽  
Josiah J. Wolf ◽  
Benjamin L. Cox ◽  
...  
Keyword(s):  
Wound Healing ◽  
Human Skin ◽  
Tissue Injury ◽  
Ex Vivo ◽  
Individual Variability ◽  
Dependent Manner ◽  
Preclinical Research ◽  
Burn Wound ◽  
Burn Wounds ◽  
Significant Difference

AbstractBackgroundEarly mechanisms underlying the progressive tissue death and the regenerative capability of burn wounds are understudied in human skin. A clinically relevant, reproducible model for human burn wound healing is needed to elucidate the early changes in the human burn wound environment. This study reports a reproducible contact burn model on human skin that explores the extent of tissue injury and healing over time, and defines the inter-individual variability in human skin to enable use in mechanistic studies on burn wound progression and healing.MethodsUsing a customized burn device, contact burns of various depths were created on human skin by two operators and were evaluated for histologic depth by three raters to determine reproducibility. Early burn wound progression and wound healing were also evaluated histologically after the thermally injured human skin was cultured ex vivo for up to 14 days.ResultsBurn depths were reproducibly generated on human skin in a temperature- or time-dependent manner. No significant difference in operator-created or rater-determined depth was observed within each patient sample. However, significant inter-individual variation was identified in burn depth in ten patient samples. Burn-injured ex vivo human skin placed into culture demonstrated differential progression of cell death and collagen denaturation for high and low temperature contact burns, while re-epithelialization was observed in superficial burn wounds over a period of 14 days.ConclusionThis model represents an invaluable tool to evaluate the inter-individual variability in early burn wound progression and wound healing to complement current animal models and enhance the translation of preclinical research to improvements in patient care.

scholarly journals EFFECT OF HEALOL OIL ON WOUND HEALING IN WISTAR RATS: A NOVEL STUDY

2018 ◽  
Vol 11 (3) ◽  
pp. 152
Author(s):  
Sujith V ◽  
Poornima G ◽  
Balaji O ◽  
Bairy Kl ◽  
Praveen K ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wistar Rats ◽  
Chronic Wounds ◽  
Statistical Significance ◽  
Silver Sulfadiazine ◽  
Histopathological Analysis ◽  
Burn Wound ◽  
Excision Wound ◽  
Burn Wounds ◽  
Wound Model

 Objective: Wound healing is a complex process, and various plant extracts have been used to study the effect of medicinal plants on wound healing. Healol oil is used in some tribal areas for ulcer healing and treatment of burn wounds. There are no animal studies done so far using healol oil to find out its role in the treatment of wounds. Hence, the aim of our study is to find the effect of healol oil in excision as well burn wounds in Wistar rats.Methods: Thirty-six Wistar rats were used, 18 rats in excision wound model and remaining in burn wound model. Each model consists of three groups of six rats each. Povidone-iodine was used as a standard control in excision wound model and silver sulfadiazine was used as a standard control in burn wound model. Healol oil was used as test drug in both the models. Period of epithelization and wound contracture rates were analyzed. Histopathological analysis of the skin tissue was done. One-way analysis of variance was used followed by Tukey’s post hoc test for statistical analysis using SPSS version 23 software, P value of <0.05 was taken as statistical significance.Results: Both standard and test groups showed significantly faster wound healing (p<0.001) compared to control rats treated with paraffin wax in both the models. In excision model standard povidone was significantly (p<0.001) better compared to healol oil whereas in burn model, silver sulfadiazine and healol oil showed comparable results with respect to period of epithelization without statistical significance (p>0.05).Conclusion: Wound healing property of healol oil is proved, and further clinical trial can be done to find out the effect of healol oil on chronic wounds due to various etiologies.

Cutaneous DNA delivery and gene expression in ex vivo human skin explants via wet-etch microfabricated microneedles

2005 ◽  
Vol 13 (7) ◽  
pp. 415-421 ◽  
Author(s):  
James Birchall ◽  
Sion Coulman ◽  
Marc Pearton ◽  
Chris Allender ◽  
Keith Brain ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Skin ◽  
Ex Vivo ◽  
Dna Delivery ◽  
Skin Explants ◽  
Wet Etch

scholarly journals Characterization of a Topically Testable Model of Burn Injury on Human Skin Explants

2020 ◽  
Vol 21 (18) ◽  
pp. 6956
Author(s):  
Olivia Gross-Amat ◽  
Marine Guillen ◽  
Damien Salmon ◽  
Serge Nataf ◽  
Céline Auxenfans
Keyword(s):  
Human Skin ◽  
Burn Injury ◽  
Ex Vivo ◽  
Drug Formulation ◽  
Burn Injuries ◽  
Major Health Problem ◽  
Constant Tension ◽  
Skin Explants ◽  
Set Up ◽  
Improved Model

Severe burn injuries remain a major health problem due to high rates of mortality, residual morbidity, and/or aesthetic damages. To find new therapies aimed at promoting a harmonious healing of skin burns, it is important to develop models which take into account the unique properties of the human skin. Based on previously described models of burn injury performed on human skin explants, we hypothesized that maintaining explants under constant tension forces would allow to more closely reproduce the pathophysiological processes of skin remodeling. We thus. Here, we set up and characterized an improved model of deep second-degree burn injury on ex vivo cultured human skin explants at air-liquid interface and maintained under conditions of constant tension forces. A spontaneous re-epithelialization of the lesion was observed 8 to 9 days post burn and was found to rely on the proliferation of basal keratinocytes at the wound edges. Collagen VII at the dermo-epidermal junction reformed along with the progression of re-epithelializatio and a synthesis of procollagen III was observed in the dermis at the wound site. These findings indicate that our model is suitable for the assessment of clinically-relevant therapies aimed at modulating the kinetics of re-epithelialization and/or the activation of fibroblasts following skin burn injuries. In this regard, we evaluated the use of a thermoreversible poloxamer hydrogel as a vehicle for topically-testable therapeutic molecules. Our data showed that, although useful for drug formulation, the p407/p188 poloxamer hydrogel induces a delay of skin re-epithelialization in humans skin explants submitted to experimental burn injury.

The Ex Vivo Skin Model as an Alternative Tool for the Efficacy and Safety Evaluation of Topical Products

2020 ◽  
Vol 48 (1) ◽  
pp. 10-22 ◽  
Author(s):  
Samara Eberlin ◽  
Michelle Sabrina da Silva ◽  
Gustavo Facchini ◽  
Gustavo Henrique da Silva ◽  
Ana Lúcia Tabarini Alves Pinheiro ◽  
...  
Keyword(s):  
Human Skin ◽  
Ex Vivo ◽  
Safety Evaluation ◽  
Test System ◽  
Dermal Matrix ◽  
Standard Size ◽  
Skin Explants ◽  
Alternative Approaches ◽  
Air Liquid Interface

The development of alternative approaches for safety and efficacy testing that avoid the use of animals is a worldwide trend, which relies on the improvement of current models and tools so that they better reproduce human biology. Human skin from elective plastic surgery is a promising experimental model to test the effects of topically applied products. As the structure of native skin is maintained, including cell population (keratinocytes, melanocytes, Langerhans cells and fibroblasts) and dermal matrix (containing collagen, elastin, glycosaminoglycans, etc.), it most closely matches the effects of substances on in vivo human skin. In this review, we present a collection of results that our group has generated over the last years, involving the use of human skin and scalp explants, demonstrating the feasibility of this model. The development of a test system with ex vivo skin explants, of standard size and thickness, and cultured at the air–liquid interface, can provide an important tool for understanding the mechanisms involved in several cutaneous disorders.

scholarly journals Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

2021 ◽  
Vol 12 ◽  
Author(s):  
Astrid Hendriks ◽  
Malgorzata Ewa Mnich ◽  
Bruna Clemente ◽  
Ana Rita Cruz ◽  
Simona Tavarini ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Human Skin ◽  
Ex Vivo ◽  
Functional Characterization ◽  
T Cell Response ◽  
Skin Microbiome ◽  
Entry Site ◽  
Healthy Human ◽  
Skin Explants

The skin is an immunocompetent tissue that harbors several kinds of immune cells and a plethora of commensal microbes constituting the skin microbiome. Staphylococcus aureus is a prominent skin pathogen that colonizes a large proportion of the human population. We currently have an incomplete understanding of the correlates of protection against S. aureus infection, however genetic and experimental evidence has shown that CD4+ T cells play a key role in orchestrating a protective anti-S. aureus immune response. A high S. aureus-specific memory CD4+ T cell response has been reported in the blood of healthy subjects. Since T cells are more abundant in the skin than in blood, we hypothesized that S. aureus-specific CD4+ T cells could be present in the skin of healthy individuals. Indeed, we observed proliferation of tissue-resident memory CD4+ T cells and production of IL-17A, IL-22, IFN-γ and TNF-β by cells isolated from abdominal skin explants in response to heat-killed S. aureus. Remarkably, these cytokines were produced also during an ex vivo epicutaneous S. aureus infection of human skin explants. These findings highlight the importance of tissue-resident memory CD4+ T cells present at barrier sites such as the skin, a primary entry site for S. aureus. Further phenotypical and functional characterization of these cells will ultimately aid in the development of novel vaccine strategies against this elusive pathogen.

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