Unburned Skin Research Articles

Challenges of PICC placement via the popliteal vein under ultrasound guidance in a patient with severe burns: A case report.

Peripherally inserted central catheters are widely used in patients with extensive burns, with the guidelines recommending insertion through unburned skin. This case report describes a patient who was burned over 88% of their surface area and suffered severe inhalation injury. For him, the popliteal vein was the only vein on unburned skin available for catheter catheterization. Based on evidence, we successfully placed a peripherally inserted central catheter through the popliteal vein under ultrasound while the patient was in the prone position and avoided associated complications.

The urgent need to achieve an optimal strategic stock of human allogeneic skin graft materials in case of a mass disaster in Poland.

A burn is a sudden injury which immediate or long-term consequences may be life-threatening for the patient. A mass disaster event may involve large numbers of severely burned patients. Patients of this type typically have a limited area of healthy, unburned skin from which an autologous split thickness skin graft could be collected. In a clinical situation of this type, it is necessary to use a particular skin substitute. Non-viable allogeneic human skin graft materials might be considered as the most suitable skin substitutes in the treatment of such patients. At present, Poland does not have a sufficient supply of human allogeneic skin graft materials to meet the needs arising from a sudden and unforeseen mass disaster. This study involved an analysis of selected mass disasters. From this an estimate was made from a verified casualty profile of the necessary minimum stock of human allogeneic skin graft materials. An insufficient amount of skin results from an inadequate number of skin donors, which in turn results from the current tissue donation system. Therefore, a proposal has been made for the organizational, legal and systemic changes required to improve the situation in Polish transplantology, with particular emphasis on skin donation. In order to achieve a strategic stock of human skin grafts, a tissue collecting transplantation team should be organized. The rights and obligations of the non-physician transplant team member should be extended. Proposals have been made for awareness campaigns (adverts, posters etc.) and educational schemes (educational video, lectures during transplant coordinator training, etc.). Finally, a proposal has been made for possible methods to deal with the logistic management of the allogeneic skin stock. The required, essential stock of human allogeneic skin in the event of a mass disaster has been estimated at 600,000 cm2.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10561-022-10001-z.

Passive Millimeter-Wave Imaging for Burns Diagnostics under Dressing Materials.

This paper presents a feasibility study of using a passive millimeter-wave imaging (PMMWI) system to assess burn wounds and the potential for monitoring the healing process under dressing materials, without their painful removal. Experimental images obtained from ex vivo porcine skin samples indicate that a ThruVision passive imager operating over the band 232–268 GHz can be used for diagnosing burns and for potentially monitoring the healing under dressing materials. Experimental images show that single and multiple burns are observed throughout dressing materials. As the interaction of millimeter-wave (MMW) radiation with the human body is almost exclusively with the skin, the major outcomes of the research are that PMMWI is capable of discriminating burn-damaged skin from unburned skin, and these measurements can be made through bandages without the imager making any physical contact with the skin or the bandage. This highlights the opportunity that the healing of burn wounds can be assessed and monitored without the removal of dressing materials. The key innovation in this work is in detecting single and multiple burns under dressing materials in noncontact with the skin and without exposing the skin to any type of manmade radiation (i.e., passive sensing technology). These images represent the first demonstration of burns wound under dressing materials using a passive sensing imager.

A deep learning model for burn depth classification using ultrasound imaging

Identification of burn depth with sufficient accuracy is a challenging problem. This paper presents a deep convolutional neural network to classify burn depth based on altered tissue morphology of burned skin manifested as texture patterns in the ultrasound images. The network first learns a low-dimensional manifold of the unburned skin images using an encoder-decoder architecture that reconstructs it from ultrasound images of burned skin. The encoder is then re-trained to classify burn depths. The encoder-decoder network is trained using a dataset comprised of B-mode ultrasound images of unburned and burned ex vivo porcine skin samples. The classifier is developed using B-mode images of burned in situ skin samples obtained from freshly euthanized postmortem pigs. The performance metrics obtained from 20-fold cross-validation show that the model can identify deep-partial thickness burns, which is the most difficult to diagnose clinically, with 99% accuracy, 98% sensitivity, and 100% specificity. The diagnostic accuracy of the classifier is further illustrated by the high area under the curve values of 0.99 and 0.95, respectively, for the receiver operating characteristic and precision-recall curves. A post hoc explanation indicates that the classifier activates the discriminative textural features in the B-mode images for burn classification. The proposed model has the potential for clinical utility in assisting the clinical assessment of burn depths using a widely available clinical imaging device.

Assessment of antibacterial activity of Syzygium aromaticum extracts, antibiotics and silver sulphadiazine ointment against pathogenic bacteria isolated from the burned and unburned skin

Assessment of antibacterial activity of Syzygium aromaticum extracts, antibiotics and silver sulphadiazine ointment against pathogenic bacteria isolated from the burned and unburned skin

Cutaneous burn diminishes beneficial effect of intravenously administered mesenchymal stem cells on acute lung injury induced by smoke inhalation in sheep

ObjectiveTo investigate effects of intravenously administered allogeneic mesenchymal stem cells (MSCs) on burn/smoke-induced lung injury. MethodsSheep were subjected to 40%, third-degree flame skin burn and smoke inhalation under deep anesthesia and analgesia. One-hour after injury, PlasmaLite A (control) or 200 million MSCs (treatment) were intravenously administered. Pulmonary oxygenation index, PaO2/FiO2 ratio, lung–lymph flow, and bloodless lung wet-to-dry weight ratio were measured. Distribution of MSCs and stromal cell-derived factor-1 (Sdf-1) protein level were determined in lung and skin tissues. Effects of burn exudate on MSCs migration were characterized. ResultsMSCs did not attenuate pulmonary dysfunction. The number of MSCs was significantly higher in lungs of sheep with smoke inhalation compared with those with burn/smoke injury. In contrast, number of MSCs was significantly higher beneath burned skin in sheep with burn/smoke than in unburned skin of sheep with smoke inhalation only. Expression of Sdf-1 protein was increased in the burned skin compared to unburned skin. Effects of burn exudate on cultured MSCs proliferation differed depending on collection time. ConclusionSkin burn diminishes beneficial effects of MSCs on smoke-induced lung injury, by promoting migration of MSCs from the pulmonary tissue to the injured skin area, possibly via expression of Sdf-1 protein.

Assessment of Bandaged Burn Wounds Using Porcine Skin and Millimetric Radiometry.

This paper describes the experimental setup and measurements of the emissivity of porcine skin samples over the band of 80–100 GHz. Measurements were conducted on samples with and without dressing materials and before and after the application of localized heat treatments. Experimental measurements indicate that the differences in the mean emissivity values between unburned skin and burned damaged skin was up to ~0.28, with an experimental measurement uncertainty of ±0.005. Measured differences in the mean emissivity values between unburned and burn damaged skin increases with the depth of the burn, indicating a possible non-contact technique for assessing the degree of a burn. The mean emissivity of the dressed burned skin was found to be slightly higher than the undressed burned skin, typically ~0.01 to ~0.02 higher. This indicates that the signature of the burn caused by the application of localized heat treatments is observable through dressing materials. These findings reveal that radiometry, as a non-contact method, is capable of distinguishing between normal and burn-damaged skin under dressing materials without their often-painful removal. This indicates the potential of using millimeter wave (MMW) radiometry as a new type of medical diagnostic to monitor burn wounds.

Burn wound classification model using spatial frequency-domain imaging and machine learning.

.Accurate assessment of burn severity is critical for wound care and the course of treatment. Delays in classification translate to delays in burn management, increasing the risk of scarring and infection. To this end, numerous imaging techniques have been used to examine tissue properties to infer burn severity. Spatial frequency-domain imaging (SFDI) has also been used to characterize burns based on the relationships between histologic observations and changes in tissue properties. Recently, machine learning has been used to classify burns by combining optical features from multispectral or hyperspectral imaging. Rather than employ models of light propagation to deduce tissue optical properties, we investigated the feasibility of using SFDI reflectance data at multiple spatial frequencies, with a support vector machine (SVM) classifier, to predict severity in a porcine model of graded burns. Calibrated reflectance images were collected using SFDI at eight wavelengths (471 to 851 nm) and five spatial frequencies (0 to ). Three models were built from subsets of this initial dataset. The first subset included data taken at all wavelengths with the planar () spatial frequency, the second comprised data at all wavelengths and spatial frequencies, and the third used all collected data at values relative to unburned tissue. These data subsets were used to train and test cubic SVM models, and compared against burn status 28 days after injury. Model accuracy was established through leave-one-out cross-validation testing. The model based on images obtained at all wavelengths and spatial frequencies predicted burn severity at 24 h with 92.5% accuracy. The model composed of all values relative to unburned skin was 94.4% accurate. By comparison, the model that employed only planar illumination was 88.8% accurate. This investigation suggests that the combination of SFDI with machine learning has potential for accurately predicting burn severity.

Camphor Burns on the Palm: An Unusual New Presentation.

Introduction:Camphor burns on the palm are uncommon and rarely encountered by a plastic surgeon.Aim:This study aims to analyze different patterns of camphor burns on the palm.Methods:Five women and one man presented with camphor burns on their palm. All patients had burns on their right palm. The shape of camphor, the duration of contact with the ignited camphor on the palm, and post-burn treatments were evaluated.Results:Three types of camphor burns were noted: Type 1 (a ring-shaped or a dome-shaped blister with unburned skin in the center), Type 2 (an oval-shaped partially thick burn with unburned skin in the center), and Type 3 (a full-thickness burn exposing the palmar fascia).Conclusion:Different types of camphor burns on the palm are described in this study. This is the first study to report ring-shaped blisters and ring-shaped partially thick camphor burns caused on the palm.

Effects of Autologous Fat and ASCs on Swine Hypertrophic Burn Scars: A Multimodal Quantitative Analysis.

Background:Hypertrophic scar formation is unpredictable and poorly understood, afflicting both the pediatric and adult populations. Treatment methods with conservative and invasive approaches have low rates of compliance and high rates of morbidity. The purpose of this study was to test a reproducible scar model and investigate a new technique of scar modification through the use of adipose- derived progenitor stromal cells (ASCs).Methods:Twenty thermal deep-partial thickness contact burns were created on the dorsum of three 8-week-old domestic swine and allowed to mature for 10 weeks. Scars were then injected with 2 cc saline, expanded autologous ASCs, or 2 cc fresh lipoaspirate and sampled at 2 week intervals up to 10 weeks postinjection. Volumetric analysis with a 3-D scanner, mechanical elasticity testing through negative pressure transduction, and standardized photography evaluation with Image J was performed. RNA sequencing was performed on scar tissue samples, cultured cells, and fresh lipoaspirate to determine relevant gene transcription regulation. Immunohistochemistry was used to verify expression level changes within the scars.Results:Volumetric analysis demonstrates a reduction in average scar thickness at 6 weeks when injected with ASCs (−1.6 cc3) and autologous fat (−1.95 cc3) relative to controls (−0.121 cc3; P < 0.05). A decrease in overall tissue compliance is observed with fat or ASC injection when compared with unburned skin at 8 weeks (35.99/37.94 versus 49.36 mm Hg × mm; P < 0.01). RNA sequencing demonstrates altered regulation of fibroblast gene expression and a decreased inflammatory profile when scars are injected with autologous fat/ASCs over controls.Conclusion:Early results suggest that autologous fat and/or ASCs may improve healing of hypertrophic scarring by altering the cellular and structural components during wound remodeling up to 20 weeks after injury. This may have beneficial applications in early treatment of large or cosmetically sensitive immature burn scars.

Cutaneous Burn Injury Promotes Shifts in the Bacterial Microbiome in Autologous Donor Skin

The cutaneous microbiome maintains skin barrier function, regulates inflammation, and stimulates wound-healing responses. Burn injury promotes an excessive activation of the cutaneous and systemic immune response directed against commensal and invading pathogens. Skin grafting is the primary method of reconstructing full-thickness burns, and wound infection continues to be a significant complication. In this study, the cutaneous bacterial microbiome was evaluated and subsequently compared to patient outcomes. Three different full-thickness skin specimens were assessed: control skin from non-burned subjects; burn margin from burn patients; and autologous donor skin from the same cohort of burn patients. We observed that skin bacterial community structure of burn patients was significantly altered compared with control patients. We determined that the unburned autologous donor skin from burn patients exhibits a microbiome similar to that of the burn margin, rather than unburned controls, and that changes in the cutaneous microbiome statistically correlate with several post-burn complications. We established that Corynebacterium positively correlated with burn wound infection, while Staphylococcus and Propionibacterium negatively correlated with burn wound infection. Both Corynebacterium and Enterococcus negatively correlated with the development of sepsis. This study identifies distinct differences in the cutaneous microbiome between burn subjects and unburned controls, and ascertains that select bacterial taxa significantly correlate with several comorbid complications of burn injury. These preliminary data suggest that grafting donor skin exhibiting bacterial dysbiosis may augment infection and/or graft failure and sets the foundation for more in-depth and mechanistic analyses in presumably "healthy" donor skin from patients requiring skin grafting procedures.

β-Adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and nonburned skin under neutral and hot environments in children.

We tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. In a randomized double-blind study, a placebo was given to eight burned children, while propranolol was given to 13 burned children with similar characteristics (mean±SD: 11.9±3years, 147±20cm, 45±23kg, 56±12% Total body surface area burned). Nonburned children (n=13, 11.4±3years, 152±15cm, 52±13kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and nonburned control skin under the two environmental conditions (23 and 34°C) via laser Doppler flowmetry. Resting SkBF was greater in burned and unburned skin compared to the nonburned control (main effect: skin, P<.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBFmax ). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose-response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and nonburned control skin (EC50 , P>.05) under either condition. Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children.

Local Burn Injury Promotes Defects in the Epidermal Lipid and Antimicrobial Peptide Barriers in Human Autograft Skin and Burn Margin

Burn injury increases the risk of morbidity and mortality by promoting severe hemodynamic shock and risk for local or systemic infection. Graft failure due to poor wound healing or infection remains a significant problem for burn subjects. The mechanisms by which local burn injury compromises the epithelial antimicrobial barrier function in the burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue, are largely unknown. The objective of this study was to establish defects in epidermal barrier function in human donor skin and burn margin, to identify potential mechanisms that may lead to graft failure and/or impaired burn wound healing. In this study, we established that epidermal lipids and respective lipid synthesis enzymes were significantly reduced in both donor skin and burn margin. We further identified diverse changes in the gene expression and protein production of several candidate skin antimicrobial peptides (AMPs) in both donor skin and burn margin. These results also parallel changes in cutaneous AMP activity against common burn wound pathogens, aberrant production of epidermal proteases known to regulate barrier permeability and AMP activity, and greater production of proinflammatory cytokines known to be induced by AMPs. These findings suggest that impaired epidermal lipid and AMP regulation could contribute to graft failure and infectious complications in subjects with burn or other traumatic injury.

Evaporative Water Loss in Superficial to Full Thickness Burns.

Increased evaporative water loss (EWL) in burn patients leads to dehydration and hypothermia. Early clinical studies performed with outdated hygrometers suggested a 17 to 75 times increased EWL in burns with contradicting results for the different burn depths.Our study proposals were: (1) obtain reliable data of the EWL of all burn depths, (2) compare these results with findings from earlier studies, (3) evaluate the usefulness of the EWL in differentiating between superficial and deep partial thickness burns, (4) determine the effect of Biobrane on the EWL of superficial partial thickness burns in vivo, and (5) evaluate the effect of the sterile incision foil Opraflex on the EWL in split skin graft donor sites. We measured the EWL of all burn depths in 28 patients under stable and recorded conditions regarding room temperature and humidity with a modern digital evaporimeter (Tewameter TM 300). For the first time in vivo, we also determined the effect of Biobrane on the EWL of burns and evaluated the EWL in split skin graft donor sites covered with Opraflex. The EWL in all burn depths was significantly increased (P < 0.001) compared with unburned skin. There was no significant difference (P > 0.05) in the EWL of superficial compared with deep partial thickness burns, whereas full thickness burns had a significantly lower EWL (P < 0.05) compared with superficial and deep partial thickness burns. Biobrane significantly reduced the EWL (P < 0.05) of superficial partial thickness burns. The EWL of Opraflex covered skin graft donor sites was significantly reduced compared with uncovered donor sites (P < 0.05). Our data suggest that the actual EWL in burns is approximately 3 times higher in full thickness burns and approximately 4 times higher in superficial and deep partial thickness burns compared with normal skin and therefore much lower than suggested previously.Because there was no significant difference in the EWL of superficial compared with deep partial thickness burns, the EWL cannot be used to differentiate between these burn depths.Biosynthetic wound dressings can significantly reduce the EWL of superficial partial thickness burns and sterile incision foil protects split skin graft donor sites from an increased EWL.

Epidermal aquaporin-3 is increased in the cutaneous burn wound

IntroductionAquaporins (AQP) are a family of transmembrane proteins that transport water and small solutes such as glycerol across cell membranes. It is a mediator of transcellular water flow and plays an important role in maintaining intra/extracellular fluid homeostasis by facilitating water transport in response to changing osmotic gradients. In the skin, AQPs permit rapid, regulated, and selective water permeability and have been demonstrated to play a role in skin hydration, cell proliferation, migration, immunity, and wound healing. However, the expression of AQP-3 in the cutaneous burn wound has never been elucidated. We sought to assess the expression of AQP-3 in patients with burn wounds. MethodsA fresh full thickness biopsy sample was taken from the center of the burn wound, the burn wound edge, and the graft donor site in 7 patients (n=21), approximately 3–7 days post injury. Fixed, paraffin embedded sections were stained using AQP-3 specific antibody and examined by immunofluorescence. Fresh samples were processed to quantify AQP-3 protein expression with Western blot analysis. ResultsThe central portion of the burn wound revealed destruction of the epidermis and dermis with no AQP-3 present. Along the burn wound edge where the epidermal architecture was disrupted, there was robust AQP-3 staining. Western blot analysis demonstrated deeper staining along the burn wound edge compared to unburned skin (control). Quantification of the protein shows a significant amount of AQP-3 expression along the burn wound edge (3.6±0.34) compared to unburned skin (2.1±0.28, N=7, *p<0.05). There is no AQP-3 expression in the burn wound center. ConclusionAQP-3 expression is increased in the burn wound following injury. While its role in wound healing has been defined, we report for the first time the effect of cutaneous burns on AQP-3 expression. Our data provides the first step in determining its functional role in burn wounds. We hypothesize that development of AQP3 targeted therapies may improve burn wound healing.

Interactive effects of acupuncture on pain and distress in major burns: An experiment with rats

This study sought to investigate the interactive effects of acupuncture on pain and distress and the local progress in the burn wound in an experimental major burn model. Forty-eight male Sprague-Dawley rats were divided into six groups: S group (sham/observation during 7 days after injury); SA group (sham/acupuncture/observation during 7 days after injury); B1 group (burns/observation during 1h after injury); BA1 group (burns/acupuncture/observation during 1h after injury); B7 group (burns/observation during 7 days after injury); and BA7 group (burns/acupuncture/observation during 7 days after injury). Pain and distress scores were evaluated throughout the study. The amounts of neutrophils and mononuclear cells were evaluated semiquantitatively, and the number of microvessels was evaluated quantitatively. Our data indicated that the average pain score of BA7 group was significantly lower than the other study groups. Histopathologic investigations indicate that the amounts of neutrophil and mononuclear cell and numbers of microvessels in the unburned skin were higher in acupuncture-applied groups. The number of microvessels in burn wounds of BA7 group was significantly higher than that of the other groups. Our data suggest that acupuncture provides low pain and distress scores in experimental rat model, and it contributes to wound healing with an enhanced angiogenesis during the acute phase of burns. Future clinical and experimental studies should be conducted to discern the benefits from acupuncture in pain management of burn patients.

Quantitative short-wave infrared multispectral imaging of in vivo tissue optical properties.

Extending the wavelength range of spatial frequency domain imaging (SFDI) into the short-wave infrared (SWIR) has the potential to provide enhanced sensitivity to chromophores such as water and lipids that have prominent absorption features in the SWIR region. Here, we present, for the first time, a method combining SFDI with unstructured (zero spatial frequency) illumination to extract tissue absorption and scattering properties over a wavelength range (850 to 1800 nm) largely unexplored by previous tissue optics techniques. To obtain images over this wavelength range, we employ a SWIR camera in conjunction with an SFDI system. We use SFDI to obtain in vivo tissue reduced scattering coefficients at the wavelengths from 850 to 1050 nm, and then use unstructured wide-field illumination and an extrapolated power-law fit to this scattering spectrum to extract the absorption spectrum from 850 to 1800 nm. Our proof-of-principle experiment in a rat burn model illustrates that the combination of multispectral SWIR imaging, SFDI, and unstructured illumination can characterize in vivo changes in skin optical properties over a greatly expanded wavelength range. In the rat burn experiment, these changes (relative to normal, unburned skin) included increased absorption and increased scattering amplitude and slope, consistent with changes that we previously reported in the near-infrared using SFDI.

Immunohistochemical analysis of neuropeptides (protein gene product 9.5, substance P and calcitonin gene-related peptide) in hypertrophic burn scar with pain and itching

BackgroundNeuropeptides have been recently reported as having an important role in wound repair, and relief from pain and itching sensation. The aim of this study was to evaluate the effect of neuropeptides on the wound healing process in hypertrophic scar formation that accompanies severe pain and itching sensation. MethodsWe collected forty-three hypertrophic scar specimens from hypertrophic scar release and skin graft under general anesthesia. Immunohistochemical stains for protein gene product (PGP) 9.5, substance P (SP), and calcitonin gene-related peptide (CGRP) were performed. Pain and itching over the scar were recorded using verbal numerical rating scale (VNRS). ResultsIn the epidermis, PGP 9.5, SP, and CGRP were significantly increased in hypertrophic scars compared with matched unburned skin. In the reticular dermis, SP and CGRP were significantly increased in hypertrophic scars compared with control. The pain and itching verbal numerical rating scale in scar group were significantly higher compared to control. In the papillary dermis, the PGP represented significant correlation with Itching P (correlation coefficient 0.698) and the SP represented significant correlation with pain N (correlation coefficient −0.671). In the reticular dermis, the SP represented significant correlation with pain N (correlation coefficient −0.614) and CGRP represented significant correlation with pain P/Itching P (correlation coefficient 0.801/0.611). ConclusionsNeuropeptides such as PGP 9.5, SP, and CGRP seem to affect scarring via sensory neurotransmission, it have a regulatory role for pain and itching sensation in hypertrophic scars.

Local Burn Injury Impairs Epithelial Permeability and Antimicrobial Peptide Barrier Function in Distal Unburned Skin*

Our objective was to characterize the mechanisms by which local burn injury compromises epithelial barrier function in burn margin, containing the elements necessary for healing of the burn site, and in distal unburned skin, which serves as potential donor tissue. Experimental mouse scald burn injury. University Research Laboratory. C57/Bl6 Male mice, 8-12 weeks old. To confirm that dehydration was not contributing to our observed barrier defects, in some experiments mice received 1 mL of saline fluid immediately after burn, while a subgroup received an additional 0.5 mL at 4 hours and 1 mL at 24 hours following burn. We then assessed skin pH and transepidermal water loss every 12 hours on the burn wounds for 72 hours postburn. Burn margin exhibited increased epidermal barrier permeability indicated by higher pH, greater transepidermal water loss, and reduced lipid synthesis enzyme expression and structural protein production up to 96 hours postburn. By contrast, antimicrobial peptide production and protease activity were elevated in burn margin. Skin extracts from burn margin did not exhibit changes in the ability to inhibit bacterial growth. However, distal unburned skin from burned mice also demonstrated an impaired response to barrier disruption, indicated by elevated transepidermal water loss and reduced lipid synthesis enzyme and structural protein expression up to 96 hours postburn. Furthermore, skin extracts from distal unburned skin exhibited greater protease activity and a reduced capacity to inhibit bacterial growth of several skin pathogens. Finally, we established that antimicrobial peptide levels were also altered in the lung and bladder, which are common sites of secondary infection in burn-injured patients. These findings reveal several undefined deficiencies in epithelial barrier function at the burn margin, potential donor skin sites, and organs susceptible to secondary infection. These functional and biochemical data provide novel insights into the mechanisms for graft failure and secondary infection after burn injury.

Effect of Glycyrrhizin on Pseudomonal Skin Infections in Human-Mouse Chimeras

In our previous studies, peripheral blood lineage−CD34+CD31+ cells (CD31+ IMC) appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs) by human epidermal keratinocytes (NHEK). In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγnull mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31+ IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31+ IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31+ IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2) of HBD-1 production by keratinocytes were not detected in cultures of patient CD31+ IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.