Burn Wound Model Research Articles

Preclinical Evaluation of Paederia foetida leaves for Burn Wound Healing Activity

The leaves of Paederia foetida are commonly used in folk remedies to treat various types of wounds, especially burn wounds. The present study was carried out to evaluate the effect of hydroalcoholic extract of Paederia foetida on experimentally induced burn wound in rats and compare the effects with known wound healing agents, Silverex ointment and Aloe veragel. An appropriate gel formulation was chosen for topical application in this burn wound model. Animals treated with Paederia foetida leaves extract showed significant reduction in period of epithelialization and wound contraction 50% as compare to control and produced comparable effect as compare to Silverex ointment and Aloe vera gel. From the study It was concluded that Paederia foetida leaves extract applied topically (2.5% and 5% gel formulation) possesses burn wound healing activity.

17 Fluid Resuscitation Effects Endothelial Glycocalyx Shedding in a Swine Model of Severe Burn Injury

17 Fluid Resuscitation Effects Endothelial Glycocalyx Shedding in a Swine Model of Severe Burn Injury

Morphological peculiarities of regeneration phases and dynamics of growth factor levels at using 2-ethyl-6-methyl-3-hydroxypyridinium n-acetyl-6-aminohexanoate for rat skin burns repairation

BACKGROUND: It was found that new derivatives of acexamic acid — N-acetyl-6-aminohexanoate of silver and 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate stimulate regeneration and mineralization of bone tissues in osteoporosis. However, to date, the effect of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate on the features of reparative histogenesis and the relationship of its stages with the levels of growth factors in regenerating tissues during skin restoration after thermal burn has not been studied.
 AIM: To estimate the morphology dynamics of skin burn healing and its relationship with the levels of vascular endothelial growth factor and basic fibroblast growth factor growth factors in rat regenerating tissues to characterize the reparative properties of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate.
 MATERIALS AND METHODS: 63 nonlinear rats were used to establish thermal burn wound model according to standard methodics. Burn wounds of the experimental group animals were treated with 2% ointment of 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate daily, control group 1 — the burns were not treated, control group 2 — ointment base was applied daily. Morphological examinations of regenerating tissues from the burn area were carried out on days 7, 14 and 21 of the experiment after standard sample preparation. The concentrations of growth factors in homogenates of regenerating tissues were determined by Enzyme Immunoassay.
 RESULTS: The inflammation phase is characterized by vascular endothelial growth factor active production and release from cells and morphologically accompanied by early neovasculogenesis in granulation tissue and significant differences in its thickness in rats of the experimental group. During the proliferation phase, activation of fibroblast reproduction and differentiation was associated with an increase in basic fibroblast growth factor levels and the maintenance of elevated vascular endothelial growth factor levels in all groups, especially high in experimental group rats. The epithelialization phase was accompanied by a statistically significant decrease in the content of basic fibroblast growth factor and vascular endothelial growth factor in regenerating skin tissues by 1.9 and 1.8 times, respectively, in comparison with the control groups.
 CONCLUSIONS: The obtained experimental data indicate 2% ointment with 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate has a reparative potential, as evidenced by the accelerated reduction both the area of burn defects and the average time for their healing in the experimental group compared to the control groups.

Chitosan thermogelation and cascade mineralization via sequential CaCO3 incorporations for wound care

Physically crosslinked hydrogels have shown great potential as excellent and eco-friendly matrices for wound management. Herein, we demonstrate the development of a thermosensitive chitosan hydrogel system using CaCO3 as a gelling agent, followed by CaCO3 mineralization to fine-tune its properties. The chitosan hydrogel effectively gelled at 37 °C and above after an incubation period of at least 2 h, facilitated by the CaCO3-mediated slow deprotonation of primary amine groups on chitosan polymers. Through synthesizing and characterizing various chitosan hydrogel compositions, we found that mineralization played a key role in enhancing the hydrogels' mechanical strength, viscosity, and thermal inertia. Moreover, thorough in vitro and in vivo assessments of the chitosan-based hydrogels, whether modified with mineralization or not, demonstrated their outstanding hemostatic activity (reducing coagulation time by >41 %), biocompatibility with minimal inflammation, and biodegradability. Importantly, in vivo evaluations using a rat burn wound model unveiled a clear wound healing promotion property of the chitosan hydrogels, and the mineralized form outperformed its precursor, with a reduction of >7 days in wound closure time. This study presents the first-time utilization of chitosan/CaCO3 as a thermogelation formulation, offering a promising prototype for a new family of thermosensitive hydrogels highly suited for wound care applications.

Evaluation of Wound Healing Activity of Hydromethanolic Crude Extract and Solvent Fractions of the Root of Verbascum Sinaiticum Benth. (Scrophulariaceae) in Swiss Albino Mice.

The roots of Verbascum sinaiticum have been used traditionally for the management of wound in different regions of Ethiopia. Despite the presence of several claims and in vitro studies regarding its role in wound healing, no scientific studies have been conducted so far. Therefore, this study aims to scientifically evaluate the wound healing activities of the crude extract and solvent fractions of the roots of Verbascum sinaiticum in Swiss albino mice. The dried root powder of Verbascum sinaiticum was extracted using 80% methanol by maceration technique. This was then fractionated with chloroform, ethyl acetate, and water. These extracts were formulated as ointment at 5% and 10% concentration by using simple base. Acute dermal toxicity was performed on mice. The wound healing potential was evaluated using excision, incision, and burn wound models. In excision wound, 10% and 5% of crude extract ointment provided a significant (P<0.001) percentage of contraction starting from day 4 and day 6 onwards respectively. Moreover, the rate of epithelialization was significantly (P<0.001) improved in 10% crude extract. In burn wound, 10% and 5% crude extract showed significant (P<0.001) wound contraction starting from day 4 and 8 onwards respectively. In both excision and burn wounds, a moderate concentration of fibroblast proliferation and collagen deposition was observed on the 10% crude extract. The 5% and 10% aqueous and ethyl acetate fractions produced a significant (P<0.001) percentage of wound contraction and shortening of epithelialization at different time points compared to simple ointment. The results of this study demonstrated that the 80% methanolic crude extract, aqueous and ethyl acetate fractions of Verbascum sinaiticum root have wound healing potential which assimilates its traditional use.

Shikonin Inhibits Vascular Extravasation and Inflammation in Burn Wounds by Regulating Wnt/β-Catenin Pathway

Objective: To explore whether shikonin can alleviate vascular leakage in burn wounds, inhibit skin inflammation, and exert protective effects on skin. Methods: A mouse skin burn wound model was routinely established, and fluorescent microspheres were injected through the tail vein 2 h before sampling to characterize the degree of vascular leakage. Dorsal skin was obtained by surgical dissection and embedded in OCT, and frozen sections were prepared. CD31 immunofluorescence was used to determine the distribution of blood vessels in burnt skin, and Ly6G immunofluorescence staining was used to determine the level of neutrophil recruitment in the skin. Results: Skin microvessels were mainly distributed in the dermis. We found that severe vascular leakage occurred in the blood vessels of the burned dermis, and shikonin significantly alleviated vascular leakage in the burned area. Furthermore, shikonin significantly inhibited neutrophil recruitment to burn sites. Most importantly, we also found that shikonin can alleviate vascular leakage and inhibit skin inflammation at burn sites through the Wnt/β-catenin signaling pathway. Conclusion: Shikonin can alleviate vascular leakage, and inhibit skin inflammation in burn wounds through the Wnt/β-catenin signaling pathway. This experimental study provides a proof-of-concept and a new avenue for the repair and treatment of burn skin vascular injuries.

Non-severe thermal burn injuries induce long-lasting downregulation of gene expression in cortical excitatory neurons and microglia.

Burn injuries are devastating traumas, often leading to life-long consequences that extend beyond the observable burn scar. In the context of the nervous system, burn injury patients commonly develop chronic neurological disorders and have been suggested to have impaired motor cortex function, but the long-lasting impact on neurons and glia in the brain is unknown. Using a mouse model of non-severe burn injury, excitatory and inhibitory neurons in the primary motor cortex were labelled with fluorescent proteins using adeno-associated viruses (AAVs). A total of 5 weeks following the burn injury, virus labelled excitatory and inhibitory neurons were isolated using fluorescence-activated cell sorting (FACS). In addition, microglia and astrocytes from the remaining cortical tissue caudal to the motor cortex were immunolabelled and isolated with FACS. Whole transcriptome RNA-sequencing was used to identify any long-lasting changes to gene expression in the different cell types. RNA-seq analysis showed changes to the expression of a small number of genes with known functions in excitatory neurons and microglia, but not in inhibitory neurons or astrocytes. Specifically, genes related to GABA-A receptors in excitatory neurons and several cellular functions in microglia were found to be downregulated in burn injured mice. These findings suggest that non-severe burn injuries lead to long lasting transcriptomic changes in the brain, but only in specific cell types. Our findings provide a broad overview of the long-lasting impact of burn injuries on the central nervous system which may help identify potential therapeutic targets to prevent neurological dysfunction in burn patients.

In vivo visualization of burn depth in skin tissue of rats using hemoglobin parameters estimated by diffuse reflectance spectral imaging.

Burn injuries represent a global public health problem that kills an estimated 180,000 people annually. Non-fatal burns result in prolonged hospitalization, disfigurement, and disability. The most common, convenient, and widely used method for assessing burn depth is physical or visual examination, but the accuracy of this method is reportedly poor (60% to 75%). Rapid, correct assessment of burn depth is very important for the optimal management and treatment of burn patients. New methods of burn depth assessment that are inexpensive, simple, rapid, non-contact, and non-invasive are therefore needed. The aim of this study was to propose an approach to visualize the spatial distribution of burn depth using hemoglobin parameters estimated from spectral diffuse reflectance imaging and to demonstrate the feasibility of the proposed approach for differentiating burn depth in a rat model of scald burn injury. The new approach to creating a spatial map of burn depth was based on canonical discriminant analysis (CDA) of total hemoglobin concentration, tissue oxygen saturation, and methemoglobin saturation as estimated from spectral diffuse reflectance images. Burns of three different degrees of severity were created in rat dorsal skin by 10-s exposure to water maintained at 70°C, 78°C, and 98°C, respectively. Spectral images for dorsal regions were acquired under anesthesia immediately after burn injury and at 24h, 48h, and 72h after injury. Most areas of images in the group with skin exposed to 70°C water and 98°C water were classified as 70°C burn and 98°C burn, respectively. In contrast, no significant difference between areas classified as 78°C burn and 98°C burn from 24h to 72h was evident in the group with skin exposed to 78°C water, suggesting that burn depth was heterogeneous. The proposed approach combining diffuse reflectance spectral imaging and CDA appears promising for differentiating 70°C burns from 78°C burns and 98°C burns, and 98°C burns from 70°C burns and 78°C burns at 24 to 72h after burn injury in a rat model of scald burn injury.

Catecholamines polymerization crosslinking for alginate-based burn wound dressings developed with ciprofloxacin and zinc oxide interactions

There is an increasing demand for stable and durable wound dressings to treat burn injuries and infections. Bioactive electrospun nanofibrous mats with antibacterial properties are promising for wound dressing usage. Electrospinning of biopolymers for wound dressing applications needs post-spinning crosslinking to prevent mat dissolution in moist wound environments. Here, we prepared durable wound dressing by using the Dopamine (DA) polymerization crosslinking in Alginate (ALG)/Polyvinyl alcohol (PVA) nanofibrous mats, which are developed by Ciprofloxacin (CIP) and Zinc oxide (ZO). The nanofibrous mats were investigated by FESEM, FTIR, mechanical strength, water contact angle, degradation, degree of swelling, and WVTR tests. The analyses demonstrate the nanofibrous mats with uniform and unbranched fibers, with a hydrophilic nature, which was porous, durable, and stable. Also, it showed the CIP and ZO addition enhanced their durability by crosslinking reinforcement. In addition, the drug release and antibacterial assays demonstrated the pH-sensitive release with more drug release at higher pH (bacterial invasion) and impressive antibacterial activity (up to 99 %). In the burn wound model in rats, the ALG/PVA/DA/CIP/ZO nanofibrous mats displayed excellent wound healing ability in wound closure and tissue regeneration. Also, complete re-epithelization and remodeling and highest collagen synthesis in histological assessment.

Reduced Expression of miR-146a Potentiates Intestinal Inflammation following Alcohol and Burn Injury.

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression. Within the intestinal epithelium, miRNAs play a critical role in gut homeostasis, and aberrant miRNA expression has been implicated in various disorders associated with intestinal inflammation and barrier disruption. In this study, we sought to profile changes in intestinal epithelial cell miRNA expression after alcohol and burn injury and elucidate their impact on inflammation and barrier integrity. Using a mouse model of acute ethanol intoxication and burn injury, we found that small intestinal epithelial cell expression of miR-146a is significantly decreased 1 d following injury. Using invitro studies, we show that reduced miR-146a promotes intestinal epithelial cell inflammation by promoting p38 MAPK signaling via increased levels of its target TRAF6 (TNFR-associated factor 6). Furthermore, we demonstrate that invivo miR-146a overexpression significantly inhibits intestinal inflammation 1 d following combined injury and potentially supports intestinal barrier homeostasis. Overall, this study highlights the important impact that miRNA expression can have on intestinal homeostasis and the valuable potential of harnessing aberrant miRNA expression as a therapeutic target to control intestinal inflammation.

Herbal Emulgel Containing Azadirachta indica (Neem) and Nigella Sativa L. (Black Cumin) Oils in Wound Management: Preclinical Investigations

Abstract Context: In wound management, traditional use of plants has received attention by the scientific community, as traditional medicines are a valuable source of affordable, comprehensive medical care. Azadirachta indica A. Juss (Neem) and Nigella sativa Linn (Black cumin) are well known versatile medicinal plants with wide spectrum of biological activity. Methods: This study was undertaken to evaluate the wound healing activity of neem oil (NO) and black cumin oil (BCO) in rats. The oils were standardized using standard procedures. Gas chromatography mass spectrometry analysis and high performance thin layer chromatography fingerprinting of oils were carried out to identify major phytoconstituents present in the oils. The oils were suitably incorporated in carbopol based emulgel formulation, evaluated for physicochemical parameters and stability. Results: The wound healing potential assessed by the measurement of wound contraction and histopathology studies in excision and burn wound models, demonstrated comparable efficacy with standard nano crystalline silver gel (0.002% w/w). This may be attributed to the presence of phytoconstituents such as nimbidin and thymoquinone present in selected oils. Polyunsaturated fatty acid profile of BCO may be responsible for stimulating the release of vascular endothelial growth factor, which plays a significant role in accelerating wound healing process. Conclusion: Topical carbopol 934 base emulgel containing natural oils such as BCO and NO have been successfully prepared for wound management. However, further studies to establish the mechanistic aspects of wound healing needs to be undertaken.

Human breast milk isolated lactic acid bacteria: antimicrobial and immunomodulatory activity on the Galleria mellonella burn wound model.

Managing burn injuries is a challenge in healthcare. Due to the alarming increase in antibiotic resistance, new prophylactic and therapeutic strategies are being sought. This study aimed to evaluate the potential of live Lactic Acid Bacteria for managing burn infections, using Galleria mellonella larvae as an alternative preclinical animal model and comparing the outcomes with a common antibiotic. The antimicrobial activity of LAB isolated from human breast milk was assessed in vitro against Pseudomonas aeruginosa ATCC 27853. Additionally, the immunomodulatory effects of LAB were evaluated in vivo using the G. mellonella burn wound infection model. In vitro results demonstrated the antimicrobial activity of Lactic Acid Bacteria against P. aeruginosa. In vivo results show that their prophylactic treatment improves, statistically significant, larval survival and modulates the expression of immunity-related genes, Gallerimycin and Relish/NF-κB, strain-dependently. These findings lay the foundation and suggest a promising alternative for burn wound prevention and management, reducing the risk of antibiotic resistance, enhancing immune modulation, and validating the potential G. mellonella as a skin burn wound model.

Fabrication and evaluation of the regenerative effect of a polycaprolactone/chitosan nanofibrous scaffold containing bentonite nanoparticles in a rat model of deep second-degree burn injury.

In the present study, we evaluated the effect of a nanofibrous scaffold including polycaprolactone (PCL), chitosan (CHT), and bentonite nanoparticles (Ben-NPS) on wound healing in order to introduce a novel dressing for burn wounds. PCL, PCL/CHT, and PCL/CHT/Ben-NPS nanofibrous scaffolds were fabricated by the electrospinning technique. Their structural and physiochemical characteristics were investigated by Fourier-transform infrared spectroscopy (FTIR) analysis, scanning electron microscopy (SEM), tensile strength, water contact angle, as well as, swelling and degradation profiles test. The disc diffusion assay was carried out to investigate the antibacterial potential of the scaffolds. In addition, the cell viability and proliferation ability of human dermal fibroblasts (HDFs) on the scaffolds were assessed using MTT assay as well as SEM imaging. The wound-healing property of the nanofibrous scaffolds was evaluated by histopathological investigations during 3,7, and 14 days in a rat model of burn wounds. SEM showed that all scaffolds had three-dimensional, beadles-integrated structures. Adding Ben-NPS into the PCL/CHT polymeric composite significantly enhanced the mechanical, swelling, and antibacterial properties. HDFs had the most cell viability and proliferation values on the PCL/CHT/Ben-NPS scaffold. Histopathological evaluation in the rat model revealed that dressing animal wounds with the PCL/CHT/Ben-NPS scaffold promotes wound healing. The PCL/CHT/Ben-NPS scaffold has promising regenerative properties for accelerating skin wound healing.

A mathematical model for simulation of cardiovascular, renal, and hormonal responses to burn injury and resuscitation.

Treating extensive burn injury requires an individually tailored resuscitation protocol that includes hourly-titrated intravenous fluid infusion to avert both hypovolemic shock and edema. Due to the complexity of burn pathophysiology and significant variability in treatment protocols, there is an ongoing effort to optimize burn resuscitation. The goal of this work is to contribute to this effort by developing a mathematical model of burn pathophysiology and resuscitation for in silico testing of burn resuscitation protocols and decision-support systems. In our previous work, we developed and validated a mathematical model consisting of volume kinetics, burn-induced perturbations, and kidney function. In this work, we expanded our previous mathematical model to incorporate novel mathematical models of cardiovascular system and hormonal system (renin-angiotensin-aldosterone (RAAS) system and antidiuretic hormone) which affect blood volume and pressure regulation. We also developed a detailed mathematical model of kidney function to regulate blood volume, pressure, and sodium levels, including components for glomerular filtration rate, reabsorption rates in nephron tubules, Tubuglomerular feedback, and myogenic mechanisms. We trained and validated the expanded mathematical model using experimental data from 15 pigs and 9 sheep with extensive burns to quantitatively evaluate its prediction accuracy for hematocrit, cardiac output, mean arterial pressure, central venous pressure, serum sodium levels, and urinary output. We then trained and tested the mathematical model using a clinical dataset of 233 human burn patients with demographic data and urinary output measurements. The mathematical model could predict all tested variables very well, while internal variables and estimated parameters were consistent with the literature. To the best of our knowledge, this is the first mathematical model of burn injury and resuscitation which is extensively validated to replicate actual burn patients. Hence, this in silico platform may complement large animal pre-clinical testing of burn resuscitation protocols. Beyond its primary purpose, the mathematical model can be used as a training tool for healthcare providers delivering insight into the pathophysiology of burn shock, and offering novel mathematical models of human physiology which can be independently used for other purposes and contexts.

Effects of dose-dependent chronic caffeine consumption in a rat burn wound model: Histopathological and immunohistochemical evaluation.

Using histopathological and immunohistochemical methods, we aimed to examine the dose-dependent effects of chronic caffeine consumption on the recovery of burn wounds in an in vivo rat model. Forty-five rats were randomly assigned to a high-dose group (20 mg/kg per day for eight weeks; n=15), a low-dose group (10 mg/kg per day for eight weeks; n=15), or a control group (n=15). The burn model was created in rats. The groups were separated into three subgroups (n=5) based on the day after injury (7th, 14th, or 21st day). The wound area, wound closure percentage, and histopathological and immunohistochemical reactivity were evaluated. Successful wound healing was noted in rats treated with low doses of caffeine, similar to the control group. Pathology revealed low re-epithelization, low inflammation, and high granulation in the high-dose group. In addition, there was a significant difference between the control and high-dose groups regarding the immunohistochemical reactivity of αVβ3 integrin, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) (P<0.05). We demonstrated that chronic caffeine consumption in rats adversely affects the recovery process of wounds in a dose-dependent manner. This effect may occur through delayed wound healing via the molecules MMP-9, αVβ3 integrin, and VEGF. Treatment that modulates these molecules can lead to enhanced and quicker recovery of damaged skin in coffee lovers.

Development of quercetin loaded silk fibroin/soybean protein isolate hydrogels for burn wound healing

Hydrogel networks composed of naturally derived polymers offer a promising solution for the development of wound dressings due to their biodegradable, biocompatible, and renewable properties. In this study, silk fibroin (SF) and soybean protein isolate (SPI) were used as the main components to create a natural SF/SPI hydrogel. To further enhance its bioactivity, quercetin was loaded into the hydrogel to form a SF/SPI-Q hydrogel. The resulting SF/SPI-Q hybrid hydrogels possessed a unique combination of advantages derived from both the natural polymers (such as excellent biocompatibility, biodegradability, and promotion of cell migration) and therapeutic drugs (including antibacterial properties and antioxidant capacity). As a result, the hydrogel effectively accelerated wound healing in an infected burn wound model. The SF/SPI-Q hydrogels accelerated epidermal regeneration, collagen deposition, and angiogenesis, facilitating the healing process of burn wounds. Moreover, they also exhibited anti-inflammatory properties, which contributed to a reduction in inflammation. Thus, the SF/SPI-Q hydrogels showed great potential as a highly effective treatment option for wound healing applications.

Testing the effects of photobiomodulation on angiogenesis in a newly established CAM burn wound model

Burn wounds are a common challenge for medical professionals. Current burn wound models hold several limitations, including a lack of comparability due to the heterogeneity of wounds and differences in individual wound healing. Hence, there is a need for reproducible in vivo models. In this study, we established a new burn wound model using the chorioallantoic membrane assay (CAM) as a surrogate model for animal experiments. The new experimental setup was tested by investigating the effects of the auspicious biophysical therapy, photobiomodulation (PBM), on the wound healing of an induced CAM burn wound with a metal stamp. PBM has been shown to positively influence wound healing through vascular proliferative effects and the increased secretion of chemotactic substances. The easily accessible burn wounds can be treated with various therapies. The model enables the analysis of ingrowing blood vessels (angiogenesis) and diameter and area of the wounds. The established model was used to test the effects of PBM on burn wound healing. PBM promoted angiogenesis in burn wounds on day 4 (p = 0.005). Furthermore, there was a not significant trend toward a higher number of vessels for day 6 (p = 0.065) in the irradiated group. Changes in diameter (p = 0.129) and the burn area (p = 0.131) were not significant. Our results suggest that CAM can be a suitable model for studying burn wounds. The novel experimental design enables reproducible and comparable studies on burn wound treatment.

Subcutaneous Anti-inflammatory Therapies to Prevent Burn Progression ina Swine Model ofContact Burn Injury.

If left untreated, burn injuries can deepen or progress in depth within the first 72 hours after injury as a result of increased wound inflammation, subsequently worsening healing outcomes. This can be especially detrimental to warfighters who are constrained to resource-limited environments with delayed evacuation times to higher roles of care and more effective treatment. Preventing this burn progression at the point of injury has the potential to improve healing outcomes but requires a field-deployable therapy and delivery system. Subcutaneous therapies known to treat inflammation delivered local to the wound site may prove to be one such avenue for success. Seven Yorkshire-cross swine received partial-thickness burn injuries using a previously established contact burn model. Each animal received one of the seven therapies: (1) saline, (2) heparin, (3) ibuprofen, (4) erythropoietin, (5) resolvin, (6) rapamycin, and (7) placental extract, all of which are either currently employed or are experimental in field use and indicated to treat inflammation. Treatments were delivered subcutaneously on the day of injury and 24 hours post-injury to simulate a prolonged field care scenario, before potential evacuation. Animals and wound development were observed for 28 days before euthanasia. Throughout the course of the study, wounds were observed macroscopically via non-invasive imaging. Histological analyses provided the critical metric of burn progression. Treatment success criteria were designated as the ability to prevent burn progression past 80% of the dermal depth in two of the three treated wounds, a clinically relevant metric of burn progression. It was determined that the applied model successfully created reproducible partial-thickness burn injuries in this porcine study. No significant differences with regard to lateral wound size or the rate of lateral wound closure were observed in any treatments. Several treatments including resolvin, rapamycin, ibuprofen, and erythropoietin successfully reduced burn progression to less than 80% of the dermal depth in two of the three wounds, 24 hours after injury. This report employs an established model of porcine contact burn injury in order to test the ability of local subcutaneous delivery of therapeutics to prevent burn progression at the point of injury, via what is believed to be the inhibition of inflammation. Several treatments successfully prevented burn progression to a full-thickness injury, potentially improving wound healing outcomes in a simulated battlefield scenario. Subcutaneously administered therapies combating burn-induced inflammation at the point of injury may serve as a field-deployable treatment modality to improve warfighter recovery and return to duty.

Fabrication and characterization of shikonin and sea buckthorn endowed nanoemulsion reinforcing elecrospun scaffolds for treatment of diabetic wounds

Electrospun polymeric nanofibers represent a novel class of wound dressing owing to their structural resemblance with the natural extracellular matrix within which pro and anti-apoptotic functions can be orchestrated comprehensively resulting in effective wound management especially in case of diabetic wounds. Recent epidemiological reports demonstrate the role of matrix metalloproteinases (MMPs) as a clear indicator of recalcitrant healing in diabetic wounds that can specifically ablate the growth factors and other pro-healing molecules hindering the healing process. Beguiling the anti-inflammatory, antimicrobial, anti-diabetic and MMP-9 modulatory properties of naphthoquinone pigments, shikonin has enticed interest of researchers in diabetic wound management. Poor solubility and photosensitivity demands novel delivery of this compound for better therapeutic efficacy. The study, thus, aims to develop reinforced shikonin and sea buckthorn oil loaded nanoemulsion (SS-NE) based chitosan scaffolds by incorporation of SS-NE as nanofiller in fibers. Subsequent characterization confirmed the stability and encapsulation of shikonin in prepared scaffold system. The results of burn wound model in diabetic Wistar rats (Type 2 diabetes) indicated that the micro-nanostructure of the fiber mats was able to promote wound healing by substantially downregulating the level of MMP-9 and stimulating collagen deposition and re-epithelization. The salient findings of the present study proposed that the bioenthused asymmetric wettable scaffolds can be employed as a propitious delivery system for treatment of diabetic wounds.

Fish Skin Grafts Affect Adenosine and Methionine Metabolism during Burn Wound Healing.

Burn wound healing is a complex process orchestrated through successive biochemical events that span from weeks to months depending on the depth of the wound. Here, we report an untargeted metabolomics discovery approach to capture metabolic changes during the healing of deep partial-thickness (DPT) and full-thickness (FT) burn wounds in a porcine burn wound model. The metabolic changes during healing could be described with six and seven distinct metabolic trajectories for DPT and FT wounds, respectively. Arginine and histidine metabolism were the most affected metabolic pathways during healing, irrespective of burn depth. Metabolic proxies for oxidative stress were different in the wound types, reaching maximum levels at day 14 in DPT burns but at day 7 in FT burns. We examined how acellular fish skin graft (AFSG) influences the wound metabolome compared to other standard-or-care burn wound treatments. We identified changes in metabolites within the methionine salvage pathway, specifically in DPT burn wounds that is novel to the understanding of the wound healing process. Furthermore, we found that AFSGs boost glutamate and adenosine in wounds that is of relevance given the importance of purinergic signaling in regulating oxidative stress and wound healing. Collectively, these results serve to define biomarkers of burn wound healing. These results conclusively contribute to the understanding of the multifactorial mechanism of the action of AFSG that has traditionally been attributed to its structural properties and omega-3 fatty acid content.