Partial-thickness Wounds Research Articles

1442 Bone marrow-derived fibrocytes contribute to type I collagen production during the early stage of cutaneous wound repair

Substantial induction of type I collagen (COL1) production is essential for regeneration of the dermal extracellular matrix during wound repair. Skin resident fibroblasts are the major cell type responsible for increased COL1. Fibrocytes are circulating bone marrow-derived cells that have the capacity to produce COL1. In tissues, fibrocytes are identified as CD45+ positive (pan hemopoietic marker) cells that express COL1. The involvement of fibrocytes in human wound healing is unclear. We have investigated the presence of fibrocytes in experimental human wounds. Partial thickness wounds were created on the buttock by ablative CO2 laser. Skin samples were obtained at baseline, 1, 3 and 5 weeks post wounding, and analyzed by immunostaining and gene expression. Immunostaining revealed that CD45+ positive cells accounted for the majority of cells, in the upper dermis at 1 week after wounding. Fifteen percent (n=8) of the CD45+ positive cells expressed COL1 protein. These CD45+/COL1+ double positive cells accounted for 26% of total COL1+ positive cells. CD45+/COL1+ double positive cells were not found 3 or 5 weeks post wounding. Consistent with these results, 14% of CD45+ positive cells that were isolated from skin one-week post wounding expressed COL1 mRNA, while no COL1 mRNA was detected in CD45+ positive cells that were isolated 3 or 5 weeks post wounding. Interestingly, fibrocytes cultured from blood or wounded skin rapidly lost CD45 expression and became indistinguishable from primary dermal fibroblasts. The above results indicate that fibrocytes rapidly home to human skin and express approx. 25% of total COL1 in early wounds. Loss of CD45 by fibrocytes may mask their full long-term contribution to wound healing. Limited fibrocyte homing to wounds, due to poor circulation, might account, in part, for weakened wound healing observed in persons with diabetes or the aged. Promoting fibrocyte entry into skin represents a novel therapeutic strategy to improve healing of refractory wounds.

526 Non-Cytotoxic Ultrathin Antimicrobial Hydrogel Dressings Containing Ionic and Metallic Silver

Preventing wound infections is a major unresolved healthcare challenge. More than 2.1 million U.S. patients seek treatment for burns annually. These wounds, when infected, do not progress through the normal healing process. To address this problem, we have developed an ultrathin microfilm dressing that delivers a non-cytotoxic, yet effective dose of antimicrobial silver ions to the wound bed. Microfilms were fabricated as polyvinyl alcohol hydrogel sheets coated with a polymeric nanofilm containing 0.1 mg/in2 of ionic and metallic silver. In contrast, commercial antimicrobial dressings Aquacel® Ag, Acticoat® and Silverlon® contain 1.2, 16.1 and 54.6 mg/in2 of silver, respectively. Cytotoxicity of microfilms was compared to that of Aquacel Ag and Silverlon using MTT cytotoxicity assay. Release of silver from these dressings over 3 days in a simulated wound fluid was also characterized. An ISO 22196-compliant study was used to measure in-vitro antimicrobial activity. A porcine wound healing study evaluated local tissue response and wound healing characteristics following repeated application of microfilm to partial-thickness wounds over 14 days. Furthermore, porcine wound colonization studies were conducted to evaluate antimicrobial activity of microfilm in wounds contaminated with 103 CFU P. aeruginosa over 5 days post-surgery. Microfilms were non-cytotoxic whereas Aquacel Ag and Silverlon were cytotoxic. This was consistent with up to 10x lower release of silver ions from microfilms. In vitro, microfilms reduced 5 Log10 units of bacterial loads, including MRSA and VRE, on their surface for >3 days. The porcine wound healing study concluded that materials of microfilms had no significant effect on epithelial growth, granulation tissue formation, critical cellular responses, or acute inflammation following multiple applications until complete wound closure. Contaminated porcine wounds treated with Telfa pads (control) had robust P. aeruginosa colonization of >105 CFU/wound, while those treated with microfilm or Acticoat had significantly less (>2 Log10 lower) bacterial burden. The difference between the CFU in microfilm and Acticoat groups was insignificant. Our antimicrobial microfilm dressing is a pioneering advance because it is effective in clearing microbial burden in wounds without causing cytotoxicity, which is in stark contrast to conventional antimicrobial dressings. Microfilms are applied to wound with each bandage change followed by longer intervals as the wounds heal. Microfilm conform intimately to the wound bed where it reduces bacterial load thus allowing normal wound healing. Microfilms slough off as wounds heal or rinsed off with saline at bandage changes.

Experimental wound ischemia does not promote pseudomonas aeruginosa biofilm formation

Introduction: It has been suggested that wound ischemia is involved in the promotion of bacterial proliferation, which is a detrimental factor in wound healing. Increasing evidence from clinical data suggests that bacteria live within biofilms on nonhealing wounds. Yet, there have been no reports clarifying the contribution of wound ischemia to biofilm formation on nonhealing wounds. Objectives: The present study addresses the question of how ischemia affects biofilm formation at wound sites. Methods: Standardized dorsal ischemic flaps were lifted and sutured on the backs of Sprague–Dawley rats. Partial thickness wounds were created on these flaps, and a suspension of Pseudomonas aeruginosa was applied to each wound. We analyzed wound exudate, histological findings, and biofilm formation. Results: The quantities of exudate from the wounds on the ischemic flaps were greater than those from control wounds. Surprisingly, in ischemic wounds, biofilm formation was diminished and leukocyte infiltration was decreased. Conclusion: Our findings demonstrate for the first time that the ischemic condition may not contribute to the development of biofilm formation on skin wounds through regulating leukocytic responses.

A Quantitative Analysis of Microcirculation in Skin Defects Covered with Topical Wound Dressings or a Newly Developed Collagen Matrix.

Innovative skin substitutes and temporary wound dressings are frequently used in the treatment of superficial and partial-thickness wounds. The aim of this study was to compare 2 commonly used temporary skin dressings with a newly developed collagen matrix to determine changes in microcirculation as measured by blood flow, hemoglobin oxygenation, and relative hemoglobin values during healing of partial-thickness skin defects. This animal study involved 28 adult male Lewis rats. On the back of each rat, 2 standardized partial-thickness skin defects were generated through a skin dermatome (n = 56). Then, wounds were treated with polylactide-based copolymer skin substitute (Suprathel, PolyMedics, Denkendorf, Germany; n = 14), biosynthetic skin dressing (Biobrane, Smith & Nephew, Hamburg, Germany; n = 14), or Collagen Cell Carrier (CCC; Naturin Viscofan, Weinheim, Germany; n = 14). The remaining control wounds were left untreated (n = 14). Perfusion dynamics were assessed every 10 days for 80 days with the O2C device (LEA Medizintechnik, Gieβen, Germany) to determine blood flow, hemoglobin oxygenation, and relative amount of hemoglobin. Blood flow was increased in all wounds for at least 30 days after wound generation. The relative amounts of hemoglobin were increased in superficial layers (2 mm) for 10 to 20 days. Hemoglobin oxygenation in the superficial layers decreased in the polylactide-based copolymer skin substitute and biosynthetic skin dressing-treated groups and initially increased in the untreated wounds and CCC groups on day 10; these values also decreased. The presented results demonstrate the complex changes in microcirculation in the course of healing partial-thickness wounds with different wound dressings and contribute to a better understanding of these wounds. However, based on the results of the study, a clear recommendation for a specific substitute is not yet possible.

Treating pain on skin graft donor sites: Review and clinical recommendations.

Split-thickness skin grafting is the most common reconstructive procedure in managing burn injuries. Harvesting split-thickness skin creates a new partial thickness wound referred to as the donor site. Pain at the donor site is reported to be one of the most distressing symptoms during the early postoperative period. Here, we (a) identify strategies for managing donor site pain, (b) assess the quality of individual studies, and (c) formulate evidence-based recommendations based on the amount and consistency of evidence. Our analysis revealed five distinct approaches to minimize donor site pain. These include: continuous subcutaneous local anesthetic infusion (three studies), subcutaneous anesthetic injection (five studies), topical agents (six studies), nonpharmacological interventions (three studies), and wound dressings (18 studies). Available randomized control trials typically evaluated pain on standardized scales (i.e. Visual Analog Scale, Numerical Rating Scale), and compared the experimental group with standard care. Recommended treatments include: (a) subcutaneous anesthetic injection of adrenaline-lidocaine; (b) ice application; (c) topical agents, such as lidocaine and bupivacaine; and (d) hydrocolloid- and polyurethane-based wound dressings accompanied with fibrin sealant. Methodologically sound randomized control trials examining the efficacy of modified tumescent solution, ropivacaine, plasma therapy, noncontact ultrasound, and morphine gels are lacking and should be a priority for future research.

Restoration of the basement membrane after wounding: a hallmark of young human skin altered with aging

In skin, the basement membrane at the dermal-epidermal junction (DEJ-BM) is an important structure that tightly binds the epidermis to the dermis, and acts as a permeability barrier that controls exchange of macromolecules. Repair of the DEJ-BM during wound healing is important for restoration of skin functional properties after wounding. Here, we used a CO2 laser to perform partial thickness wounds in human volunteers, and directly compared wound repair in healthy young and aged individuals, focusing on the DEJ-BM. Our results show that the DEJ-BM is restored within four weeks after partial thickness wounds in young adults. We identified laminin-γ2 as preferred substrate for keratinocytes during reepithelialization of partial thickness human wounds. Laminin-γ2 is expressed continuously by migrating keratinocytes during reepithelialization, whereas collagen IV and collagen VII are deposited after wound closure. In contrast, our study shows that the DEJ-BM restoration following wounding is deficient in elderly individuals. Specifically, COL7A2 was barely increased during wound repair in aged skin and, as a result, the DEJ-BM in elderly skin was not restored and showed abnormal structure. Our data suggest that ameliorating the quality of the DEJ-BM restoration is a promising therapeutic approach to improve the quality of repaired skin in the elderly.

Electrophoto-Biomodulation in Aesthetic Treatment of Postburn Hypopigmentation: Clinical Response in Relation to Histopathological Changes.

Hypopigmentation is a troublesome often-permanent sequelae after burn injury, particularly in dark races. A number of methods have been described to treat this phenomenon. In this work, we are going to study the effect of E light (intensive pulsed light+radiofrequency+cooling) in repigmentation of partial thickness and full thickness burn wounds in adult patients and light microscopic changes of biopsy material at various stages of repigmentation. In this study, 24 patients with postburn hypopigmentation were selected and E light was used, using different filters, according to the skin color. The intensive pulsed light fluence varied between 38 and 42 J. Radiofrequency fluencies varied between 6 and 10 J, and the spot diameter was 8 × 32 mm. Pulse durations of 2 to 7 milliseconds and pulse delays of 15 to 30 milliseconds were used on all patients.The patients were evaluated by comparing pretreatment and posttreatment photos. Skin biopsies were taken from depigmented area before and after interventions. Melanocytes were immunostained using Hwenty-four homatropine methylbromide 45 and were counted in ×200 magnification fields. Melanin can be demonstrated after staining with hematoxylin and eosin. Seventeen cases were evaluated as excellent, 4 cases were evaluated as good, and 3 cases were evaluated as fair, but all patients stressed that their wounds have been improved.Light microscopy at 6 weeks posttreatment also confirmed the increased melanocyte number per field in all cases. E light induced significant overall clinical improvement in postburn hypopigmentation, particularly when E light was applied early after burn.

Differential effects of Losartan and Atorvastatin in partial and full thickness burn wounds.

Healing of burn wounds is often associated with scar formation due to excessive inflammation and delayed wound closure. To date, no effective treatment is available to prevent the fibrotic process. The Renin Angiotensin System (RAS) was shown to be involved in fibrosis in various organs. Statins (e.g. Atorvastatin), Angiotensin receptor antagonists (e.g. Losartan) and the combination of these drugs are able to reduce the local RAS activation, and reduced fibrosis in other organs. We investigated whether inhibition of the RAS could improve healing of burn wounds by treatment with Atorvastatin, Losartan or the combination of both drugs. Therefore, full and partial thickness burn wounds were inflicted on both flanks of Yorkshire pigs. Oral administration of Atorvastatin, Losartan or the combination was started at post-burn day 1 and continued for 28 days. Full thickness wounds were excised and transplanted with an autologous meshed split-thickness skin graft at post-burn day 14. Partial thickness wounds received conservative treatment. Atorvastatin treatment resulted in enhanced graft take and wound closure of the full thickness wounds, faster resolution of neutrophils compared to all treatments and reduced alpha-smooth muscle actin positive cells compared to control treatment. Treatment with Losartan and to a lesser extent the combination therapy resulted in diminished graft take, increased wound contraction and poorer scar outcome. In contrast, Losartan treatment in partial thickness wounds decreased the alpha-smooth muscle actin+ fibroblasts and contraction. In conclusion, we showed differential effects of Losartan and Atorvastatin in full and partial thickness wounds. The extensive graft loss seen in Losartan treated wounds is most likely responsible for the poor clinical outcome of these full thickness burn wounds. Therefore, Losartan treatment should not be started before transplantation in order to prevent graft loss. Atorvastatin seems to accelerate the healing process in full thickness wounds possibly by dampening the pro-inflammatory response.

The Feasibility of a Handheld Electrospinning Device for the Application of Nanofibrous Wound Dressings.

Objectives: The aim of this study was to determine the feasibility of a portable electrospinning device for the application of wound dressings. Approach: Four polymer nanofibers dressings were applied on superficial partial thickness wounds to a porcine model and compared with a traditional paraffin tulle gras dressing. The polymer nanofibrous dressings were applied using a handheld portable electrospinning device activated at a short distance from the wound. The partial thickness donor sites were evaluated on day 2, 7, and 14 when dressings were removed and tissue samples were taken for histological examination. Results: No significant difference was detected between the different electrospun nanofibrous dressings and traditional paraffin tulle gras. Desirable characteristics of the electrospun nanofiber dressing group included nontouch technique, ease of application, adherence and reduction in wound edema and inflammation. There was no delayed wound healing or signs of infection reported in both the electrospun nanofiber and traditional tulle gras dressings. Innovation: Used on partial thickness wounds, polymer electrospun nanofiber dressings provide excellent surface topography and are a nontouch, feasible, and safe method to promote wound healing with the potential to reduce wound infections. Such custom-made nanofibrous dressings have implications for the reduction of pain and trauma, number of dressing changes, scarring, and an added cost benefit. Conclusion: We have demonstrated that this portable handheld electrospinning device can be utilized for different formulations and materials and customized according to the characteristics of the target wound at the various stages of wound healing.

Second harmonic generation imaging of corneal stroma after infection by Pseudomonas aeruginosa

Pseudomonas aeruginosa is a pathogenic gram-negative organism that has the ability to cause blinding corneal infections following trauma and during contact lens wear. In this study, we investigated the directional movement and orientation of an invasive corneal isolate of P. aeruginosa in the corneal stroma during infection of ex vivo and in vivo rabbit corneas using multiphoton fluorescence and second harmonic generation (SHG) imaging. Ex vivo, rabbit corneas were subject to three partial thickness wounds prior to inoculation. In vivo, New Zealand white rabbits were fit with P. aeruginosa laden contact lenses in the absence of a penetrating wound. At all time points tested, infiltration of the corneal stroma by P. aeruginosa revealed a high degree of alignment between the bacteria and collagen lamellae ex vivo (p < 0.001). In vivo, P. aeruginosa traveled throughout the stroma in discrete regions or bands. Within each region, the bacteria showed good alignment with collagen lamellae (P = 0.002). Interestingly, in both the in vitro and in vivo models, P. aeruginosa did not appear to cross the corneal limbus. Taken together, our findings suggest that P. aeruginosa exploits the precise spacing of collagen lamellae in the central cornea to facilitate spread throughout the stroma.

Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program

The clinical significance of timely re-epithelialization is obvious in burn care, since delayed wound closure is enhancing the risk of wound site infection and extensive scarring. Topical treatments that accelerate wound healing are urgently needed to reduce these sequelae. Evidence from preliminary studies suggests that betulin can accelerate the healing of different types of wounds, including second degree burns and split-thickness skin graft wounds.The goal of this combined study program consisting of two randomized phase III clinical trials in parallel is to evaluate whether a topical betulin gel (TBG) is accelerating re-epithelialization of split-thickness skin graft (STSG) donor site wounds compared to standard of care.Two parallel blindly evaluated, randomised, controlled, multicentre phase III clinical trials were performed in adults undergoing STSG surgery (EudraCT nos. 2012-003390-26 and 2012-000777-23). Donor site wounds were split into two equal halves and randomized 1:1 to standard of care (a non-adhesive moist wound dressing) or standard of care plus TBG consisting of 10% birch bark extract and 90% sunflower oil (Episalvan, Birken AG, Niefern-Oeschelbronn, Germany). The primary efficacy assessment was the intra-individual difference in time to wound closure assessed from digital photographs by three blinded experts.A total of 219 patients were included and treated in the two trials. Wounds closed faster with TBG than without it (15.3 vs. 16.5 days; mean intra-individual difference=−1.1 days [95% CI, −1.5 to −0.7]; p<0.0001).This agreed with unblinded direct clinical assessment (difference=−2.1 days [95% CI, −2.7 to −1.5]; p<0.0001). Adverse events possibly related to treatment were mild or moderate and mostly at the application site.TBG accelerates re-epithelialization of partial thickness wounds compared to the current standard of care, providing a well-tolerated contribution to burn care in practice.

Effectiveness of a polyhexanide irrigation solution on methicillin-resistant Staphylococcus aureus biofilms in a porcine wound model.

Irrigation and removal of necrotic debris can be beneficial for proper healing. It is becoming increasingly evident that wounds colonized with biofilm forming bacteria, such as Staphylococcus aureus (SA), can be more difficult to eradicate. Here we report our findings of the effects of an irrigation solution containing propyl-betaine and polyhexanide (PHMB) on methicillin-resistant Staphylococcus aureus (MRSA) biofilms in a porcine wound model. Thirty-nine deep partial thickness wounds were created with six wounds assigned to one of six treatment groups: (i) PHMB, (ii) Ringer's solution, (iii) hypochlorous acid/sodium hypochlorite, (iv) sterile water, (v) octenidine dihydrochloride, and (vi) octenilin. Wounds were inoculated with MRSA and covered with a polyurethane dressing for 24 hours to allow biofilm formation. The dressings were then removed and the wounds were irrigated twice daily for 3 days with the appropriate solution. MRSA from four wounds were recovered from each treatment group at 3 days and 6 days hours after initial treatment. Irrigation of wounds with the PHMB solution resulted in 97·85% and 99·64% reductions of MRSA at the respective 3 days and 6 days assessment times when compared to the untreated group. Both of these reductions were statistically significant compared to all other treatment groups (P values <0·05).

Noninvasive Techniques for the Determination of Burn Severity in Real Time.

Visual diagnosis of second-degree burns has proven inadequate for determining the appropriate treatment regimen. Although multiple noninvasive imaging techniques have shown promise for providing information about burn wound severity, the ideal technology to aid burn wound excision would provide real-time readouts. Herein, the authors examine a high-resolution infrared (IR) camera (thermography) and a multiprobe adapter system (MPAS-6; transepidermal evaporative water loss, colorimetry) to assess their usefulness in predicting burn severity. Contact burn wounds of increasing severity were created in a porcine model. Wounds were assessed for 4 days with an IR camera and MPAS-6. In addition, each day, the burn wounds were biopsied for histological analysis to determine burn depth for correlation with noninvasive measures. Surface temperatures decreased with increasing burn severity, which was associated with increasing transepidermal evaporative water loss. Melanin content correlated with the depth of collagen coagulation and was bimodal, with superficial and full-thickness burns having higher values than deep partial thickness wounds. Erythema content was highest in superficial burns and negatively correlated with necrosis (high-mobility group box protein 1 expression). Importantly, surface temperature taken on every single day after injury was predictive of all histologically determined measurements of burn depth (ie, collagen coagulation, apoptosis, necrosis, vascular occlusion). The results indicate that IR imaging and skin quality probes can be used to support the diagnosis of burn severity. Most importantly, IR measurements gave insight into both the zone of coagulation and the zone of stasis on every postburn day studied.

Involvement of eIF6 in external mechanical stretch-mediated murine dermal fibroblast function via TGF-β1 pathway.

External mechanical loading on a wound commonly increases fibrosis. Transforming growth factor-β1 (TGF-β1) has been implicated in fibrosis in various models, including the mechanical force model. However, the underlying mechanism is unclear. Our previous experiments suggested that eukaryotic initiation factor 6 (eIF6) acted as a regulator of TGF-β1 expression, and negatively impact on collagen synthesis. Our current results showed that external mechanical stretching significantly increased COL1A1, TGF-β1 and eIF6 expression as well as dermal fibroblasts proliferation, both in vitro and in vivo. eIF6 –deficient (eIF6+/−) cells exhibited significantly higher levels of COL1A1, and these levels increased further with external mechanical stretching, suggesting that mechanical stretching plays a synergistic role in promoting COL1A1 expression in eIF6+/− cells. Inhibition of TGFβR I/II by LY2109761 decreased COL1A1 protein expression in eIF6+/− dermal fibroblasts in a cell stretching model, and attenuated granulation tissue formation in partial thickness wounds of eIF6+/− mice. These data suggest that mechanical stretching has a synergistic role in the expression of COL1A1 in eIF6+/− cells, and is mediated by activation of TGFβRI/II. Taken together, our results indicate that eIF6 may be involved in external mechanical force-mediated murine dermal fibroblast function at least partly through the TGF-β1 pathway.

Evaluation of Moringa oleifera seed biopolymer-PVA composite hydrogel in wound healing dressing

Polysaccharide-based hydrogel scaffolds have emerged as promising candidates for skin regeneration. However, for restoring the integrity of the injured tissue, an appropriate balance of moisture and bioactivity needs to be maintained at the wound surface. Though several researchers have designed hydrogels from synthetic or natural resources, their applicability is restricted due to availability, cost and restricted properties suitable to specific wound types. In this study, a novel hydrogel composed of polysaccharide polymer from Moringa oleifera seeds and polyvinyl alcohol (MSP/PVA) was synthesized as a wound dressing material. The hydrogel was characterized using FTIR and XRD and evaluated for its fluid handling properties. It could absorb 5.7 g H2O g−1 dry weight with 20–30 % moisture being retained even after 24 h. Its good water absorption and donation ability make it appropriate for dry, necrotic and slightly exuding wounds. Its breathability and water vapor transmission rate extend it applicability to management of burns. The hydrogel exhibited hemocompatibility, antibacterial activity, bacterial impermeability, antioxidant activity and iron chelation that might help healing chronic wounds as well. It was biodegradable. In vivo wound healing showed that the rate of wound reduction and closure was accelerated with rapid re-epithelialization of partial thickness wounds in 6 days without scar formation. In vitro povidone–iodine loading and release studies showed that the iodine release followed Fickian diffusion process. The MSP/PVA hydrogel holds promise for management of dry, necrotic, slightly exuding, chronic wounds, burns and thus appears to be an economical alternative worth industrial exploitation.

Abstract: Even Better Than the Real Thing? The Use of Xenografting in Pediatric Patients with Scald Injury -- A Single-Institution, 10-Year Review

INTRODUCTION: Scald injuries remain the most common type of burn in children, but best practices continue to evolve. Over 250,000 children are burned each year in the United States, and 100,000 of these are scald burns.1 The use of Xenografting in burns has been described as early as 1880,2 followed by the description of split- or intermediate-thickness skin grafts in 1929.3 Depending on depth of injury, management can range from non-operative wound care to excision and autografting. In 2004, we introduced xenografting for intermediate partial-thickness wounds at our institution. We report our 10-year experience with pediatric scald burns, comparing Xenografting to Autografting. METHODS: Using prospectively collected data submitted to the National Burn Repository, verified by individual chart review, we identified all patients < 18 years old, admitted to our burn center, who sustained scald burns from 2004–2013. Patients were divided into three cohorts, based on wound closure method (Autograft, Xenograft, Non-Op) and compared by two tailed t-test and chi-square analysis. RESULTS: 1867 children with scald burns were admitted from 2004–2013. Compared to Autografting, patients who underwent xenografting had a similar TBSA, but lower incidence of hospital-acquired infections (HAIs), shorter ICU and facility stays, less expensive hospitalizations, and decreased development of hypertrophic scar formation or need for reconstruction. However compared to the Non-Op group, Xenografting patients had a larger TBSA, higher cost, and LOS. CONCLUSIONS: Xenografting appears to be a reasonable option for patients with partial-thickness scald injuries. The cost, LOS, HAIs, and ICU days for the Xenografting cohort fell in-between the Non-Op and Autografting cohorts, as would be expected. While non-operative management may be appropriate for small/superficial burns, and Autografting may be required for large/deep burns, xenografting provides rapid wound closure. Xenografting also permits earlier hospital discharge, reduces need for reconstruction, and should strongly be considered as first line therapy for intermediate-depth pediatric scald injuries. DISCLOSURE/FINANCIAL SUPPORT:None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript. REFERENCES: 1. “Pediatric Burns Fact Sheet”; The Burn Foundation. http://www.burnfoundation.org/programs/resource.cfm?c=1&a=12. Feb 3rd, 2015. 2. Lee EW. Zoografting in a burn case. Boston Med Surg 1880;103:260. 3. Diegidio P. Chapter 1: The Use and Uses of Large Split Skin Grafts of Intermediate Thickness by Blair VP, and Brown JB (1929) in 50 Studies Every Plastic Surgeon Should Know. Edited by C.S. Hultman. CRC Press, Taylor & Francis Group; Boca Raton, FL (2014).

Imaging mass spectrometry for accessing molecular changes during burn wound healing.

The spatiotemporal analysis of the proteomic profile during human wound healing is a critical investigative step that can establish the complex interplay of molecular events that comprise the local response to burn injury. Partial-thickness wound samples with adjacent "normal" skin were collected from twenty-one patients with burn wounds and examined across a time spectrum ranging from the acute injury period at 3, 6, 11 days to the later hypertrophic scar period at 7 and 15 months. The techniques used for histology-directed tissue analyses highlighted inflammatory protein markers at the early time points after injury with diminished expression as burn wounds progressed into the proliferative phase. The datasets show the usefulness of MALDI MS and imaging mass spectrometry as discovery approaches to identify and map the cutaneous molecular sequence that is activated in response to the unique systemic inflammatory response following burn trauma. This information has the potential to define the unique factors that predispose human burn victims to disfiguring hypertrophic scar formation.

In vivo methods to evaluate a new skin protectant for loss of skin integrity.

A new skin protectant was developed for use on conditions involving partial-thickness skin loss such as severe incontinence-associated dermatitis. This new formulation is based on a cyanoacrylate chemistry designed to polymerize in situ and create a breathable film able to protect the skin surface from external irritants. This film provides an environment favorable for healing to occur beneath the film. To evaluate the characteristics of the novel chemistry, we devised a preclinical testing strategy comprising three different animal models. The data from all three models was considered collectively to create an overall assessment of effectiveness. A guinea pig model was used to evaluate the barrier efficacy of the new product in protecting intact skin from irritation. A porcine partial-thickness wound model was used to evaluate the efficacy of the product in helping control minor bleeding and exudate. A similar model was also used to assess the process of reepithelialization in the continued presence of an irritant. In the first model, untreated sites had 8.5 times more irritation than sites covered with the new product (p < 0.001). In the second model, a single application of the new product successfully attached to intact peri-wound skin and to denuded, weepy skin. It significantly reduced the amount of fluid weeping from the wounds (p ≤ 0.001) and continued to perform throughout a 96 hours experiment. In the third model, the percent of reepithelialization was significantly greater for the wounds covered with the new product than for the control wounds (p = 0.003; on average, 18.3% greater, with a 95% confidence interval of 9.2% to 27.5%). These results suggest that the new skin protectant protects intact and denuded skin from irritants and provides an environment favorable to healing, offering promise for the management of various conditions involving loss of epidermis.

Enhancement of Wound Healing by Non-Thermal N2/Ar Micro-Plasma Exposure in Mice with Fractional-CO2-Laser-Induced Wounds.

Micro-plasma is a possible alternative treatment for wound management. The effect of micro-plasma on wound healing depends on its composition and temperature. The authors previously developed a capillary-tube-based micro-plasma system that can generate micro-plasma with a high nitric oxide-containing species composition and mild working temperature. Here, the efficacy of micro-plasma treatment on wound healing in a laser-induced skin wound mouse model was investigated. A partial thickness wound was created in the back skin of each mouse and then treated with micro-plasma. Non-invasive methods, namely wound closure kinetics, optical coherence tomography (OCT), and laser Doppler scanning, were used to measure the healing efficiency in the wound area. Neo-tissue growth and the expressions of matrix metallopeptidase-3 (MMP-3) and laminin in the wound area were assessed using histological and immunohistochemistry (IHC) analysis. The results show that micro-plasma treatment promoted wound healing. Micro-plasma treatment significantly reduced the wound bed region. The OCT images and histological analysis indicates more pronounced tissue regrowth in the wound bed region after micro-plasma treatment. The laser Doppler images shows that micro-plasma treatment promoted blood flow in the wound bed region. The IHC results show that the level of laminin increased in the wound bed region after micro-plasma treatment, whereas the level of MMP-3 decreased. Based on these results, micro-plasma has potential to be used to promote the healing of skin wounds clinically.

Reduced cell cohesiveness of outgrowths from eccrine sweat glands delays wound closure in elderly skin.

SummaryHuman skin heals more slowly in aged vs. young adults, but the mechanism for this delay is unclear. In humans, eccrine sweat glands (ESGs) and hair follicles underlying wounds generate cohesive keratinocyte outgrowths that expand to form the new epidermis. Here, we compared the re‐epithelialization of partial‐thickness wounds created on the forearm of healthy young (< 40 yo) and aged (> 70 yo) adults. Our results confirm that the outgrowth of cells from ESGs is a major feature of repair in young skin. Strikingly, in aged skin, although ESG density is unaltered, less than 50% of the ESGs generate epithelial outgrowths during repair (vs. 100% in young). Surprisingly, aging does not alter the wound‐induced proliferation response in hair follicles or ESGs. Instead, there is an overall reduced cohesiveness of keratinocytes in aged skin. Reduced cell–cell cohesiveness was most obvious in ESG‐derived outgrowths that, when present, were surrounded by unconnected cells in the scab overlaying aged wounds. Reduced cell–cell contact persisted during the repair process, with increased intercellular spacing and reduced number of desmosomes. Together, reduced outgrowths of ESG (i) reduce the initial number of cells participating in epidermal repair, (ii) delay wound closure, and (iii) lead to a thinner repaired epidermis in aged vs. young skin. Failure to form cohesive ESG outgrowths may reflect impaired interactions of keratinocytes with the damaged ECM in aged skin. Our findings provide a framework to better understand the mediators of delayed re‐epithelialization in aging and further support the importance of ESGs for the repair of human wounds.