Cold atmospheric plasma (CAP) devices generate an ionized gas with highly reactive species and electric fields at ambient air pressure and temperature. A flexible dielectric barrier discharge (DBD) ...was developed as an alternative antimicrobial treatment for chronic wounds. Treatment of
Staphylococcus aureus
in collagen-elastin matrices with CAP for 2 min resulted in a 4 log reduction. CAP treatment was less effective on
S. aureus
on dermal samples. CAP did not affect cellular activity or DNA integrity of human dermal samples when used for up to 2 min. Repeated daily CAP treatments for 2 min lowered cellular activity of dermal samples to 80% after 2 to 4 days, but this was not significant. Repeated treatment of ex vivo human burn wound models with CAP for 2 min did not affect re-epithelialization. Intact skin of 25 healthy volunteers was treated with CAP for 3× 20” to determine safety. Although participants reported moderate pain scores (numerical rating scale 3.3), all volunteers considered the procedure to be acceptable. Severe adverse events did not occur. CAP treatment resulted in a temporarily increased local skin temperature (≈3.4°C) and increased erythema. Lowering the plasma power resulted in a significantly lower erythema increase. Good log reduction (2.9) of bacterial load was reached in 14/15 volunteers artificially contaminated with
Pseudomonas aeruginosa
. This study demonstrated the in vitro and in vivo safety and efficacy in bacterial reduction of a flexible cold plasma device. Trial registration number NCT03007264, January 2, 2017
Key Points
• CAP strongly reduced bacterial numbers both in vitro and in vivo.
• Re-epithelialization of burn wound models was not affected by repeated CAP.
• CAP treatment of intact skin was well tolerated in volunteers.
Antimicrobial peptides (AMPs) or host defense peptides protect the host against various pathogens such as yeast, fungi, viruses and bacteria. AMPs also display immunomodulatory properties ranging ...from the modulation of inflammatory responses to the promotion of wound healing. More interestingly, AMPs cause cell disruption through non-specific interactions with the membrane surface of pathogens. This is most likely responsible for the low or limited emergence of bacterial resistance against many AMPs. Despite the increasing number of antibiotic-resistant bacteria and the potency of novel AMPs to combat such pathogens, only a few AMPs are in clinical use. Therefore, the current review describes (i) the potential of AMPs as alternatives to antibiotics, (ii) the challenges toward clinical implementation of AMPs and (iii) strategies to improve the success rate of AMPs in clinical trials, emphasizing the lessons we could learn from these trials.
Summary Hypertrophic scars and keloids can be aesthetically displeasing and lead to severe psychosocial impairment. Many invasive and non-invasive options are available for the plastic (and any ...other) surgeon both to prevent and to treat abnormal scar formation. Recently, an updated set of practical evidence-based guidelines for the management of hypertrophic scars and keloids was developed by an international group of 24 experts from a wide range of specialities. An initial set of strategies to minimize the risk of scar formation is applicable to all types of scars and is indicated before, during and immediately after surgery. In addition to optimal surgical management, this includes measures to reduce skin tension, and to provide taping, hydration and ultraviolet (UV) protection of the early scar tissue. Silicone sheeting or gel is universally considered as the first-line prophylactic and treatment option for hypertrophic scars and keloids. The efficacy and safety of this gold-standard, non-invasive therapy has been demonstrated in many clinical studies. Other (more specialized) scar treatment options are available for high-risk patients and/or scars. Pressure garments may be indicated for more widespread scarring, especially after burns. At a later stage, more invasive or surgical procedures may be necessary for the correction of permanent unaesthetic scars and can be combined with adjuvant measures to achieve optimal outcomes. The choice of scar management measures for a particular patient should be based on the newly updated evidence-based recommendations taking individual patient and wound characteristics into consideration.
Burn injury has severe impact on the physiologic homeostasis. Platelet counts show a distinct course post-burn injury, with a nadir at day 3 followed by a thrombocytotic period with at peak at day ...15, with a gradual return to normal. So far, it is unknown how the functionality and activational status of platelets develop post burn. In this study, we investigated if the function, activation and growth factor content of platelets of burn patients are affected and how this evolves in time. Six burn patients with over 15% total burned surface area were followed during 1 month. Standard hematological and coagulation analyses, thromboelastography (TEG), platelet-function analyzer-100 (PFA), several platelet activation parameters (CD62P-CD63, AnnexinV) and growth factors (TGFb1, VEGF, PDGF-AB/BB, EGF, TGFb2, FGF-2, PDGF-AA) analyses were performed. TEG analyses showed procoagulant changes. PFA-100 analyses were nearly all within normal range. CD62P and CD63 and Annexin-V indicated no clear activation of platelets. Growth factor content followed the same course as the platelet count, reflecting a constant growth factor per platelet ratio. Concluding, platelets post burn-injury appears to be functional and not overly activated. However, burn patients seem to remain in a procoagulant state for an extensive period, which may impact their pathology.
Abstract Objective This study assessed the role of self-reported facial scar severity as a possible influencing factor on self-esteem and depressive symptoms in patients with facial burns. Method A ...prospective multicentre cohort study with a 6 months follow-up was conducted including 132 patients with facial burns. Patients completed the Patient and Observer Scar Assessment Scale, the Rosenberg Self-esteem Scale and the Hospital Anxiety and Depression Scale. Structural Equation Modeling was used to assess the relations between depressive symptoms, self-esteem and scar severity. Results The model showed that patient-rated facial scar severity was not predictive for self-esteem and depressive symptoms six months post-burn. There was, however, a significant relationship between early depressive symptoms and both patient-rated facial scar severity and subsequent self-esteem. The variables in the model accounted for 37% of the variance in depressive symptoms six months post-burn and the model provided a moderately well-fitting representation of the data. Conclusion The study suggests that self-esteem and depressive symptoms were not affected by self-reported facial scar severity but that earlier depressive symptoms were indicative for a more severe self-reported facial scar rating. Therefore, routine psychological screening during hospitalisation is recommended in order to identify patients at risk and to optimise their treatment.
Background Scar formation remains a major clinical problem; therefore, various therapies have been developed to improve scar quality. To evaluate the effectiveness of these therapies, objective ...measurement tools are necessary. An appropriate, objective measuring instrument for assessment of surface roughness is not yet available in a clinical setting. The Phaseshift Rapid In Vivo Measurement of the Skin (PRIMOS) (GFMesstechnik GmbH, Teltow, Germany) could be such an instrument. This device noninvasively produces a 3-dimensional image of the skin microtopography and measures surface roughness. Objective The aim of this study was to investigate the reliability and validity of the PRIMOS for objective and quantitative measurement of surface roughness of skin and scars. Methods Three observers assessed skin and burn scars in 60 patients using the PRIMOS and a subjective scale, the Patient and Observer Scar Assessment Scale. Reliability was tested using the intraclass correlation of intraobserver and interobserver measurements. An intraclass correlation coefficient of 0.7 or greater was required for reliable results. To test validity, scores of the PRIMOS were compared with scores of the subjective scale (Pearson correlation). A Pearson correlation coefficient greater than 0.6 was considered a strong positive correlation. Results All 3 surface roughness parameters of the PRIMOS showed good intraobserver and interobserver reliability for skin and scars (intraclass correlation coefficient arithmetic mean of surface roughness > 0.85, mean of 5 highest peaks and 5 deepest valleys from entire measuring field > 0.88, peak count > 0.86). The parameter arithmetic mean of surface roughness showed a strong correlation with the subjective score (Pearson arithmetic mean of surface roughness 0.70; mean of 5 highest peaks and 5 deepest valleys from entire measuring field 0.53; peak count 0.54). Limitations The reliability and validity of the PRIMOS were only tested on skin and burn scars, not in other dermatologic diseases. Conclusions The PRIMOS is a valid and reliable tool for objective noninvasive evaluation of surface roughness of both skin and burn scars.
Platelet rich plasma (PRP) is blood plasma with a platelet concentration above baseline. When activated, PRP releases growth factors involved in all stages of wound healing, potentially boosting the ...healing process. To expand our knowledge of the effectiveness of PRP, it is crucial to know the content and composition of PRP products. In this study, growth factor quantification measurements of PRP from burn patients and gender- and age-matched controls were performed. The PRP of burn patients showed levels of growth factors comparable to those of the PRP of healthy volunteers. Considerable intra-individual variation in growth factor content was found. However, a correlation was found between the platelet count of the PRP and most of the growth factors measured.
Standard treatment for large burns is transplantation with meshed split skin autografts (SSGs). A disadvantage of this treatment is that healing is accompanied by scar formation. Application of ...autologous epidermal cells (keratinocytes and melanocytes) may be a suitable therapeutic alternative, since this may enhance wound closure and improve scar quality. A prospective, multicenter randomized clinical trial was performed in 40 adult patients with acute full thickness burns. On two comparable wound areas, conventional treatment with SSGs was compared to an experimental treatment consisting of SSGs in combination with cultured autologous epidermal cells (ECs) seeded in a collagen carrier. The primary outcome measure was wound closure after 5–7 days. Secondary outcomes were safety aspects and scar quality measured by graft take, scar score (POSAS), skin colorimeter (DermaSpectrometer®) and elasticity (Cutometer®). Wound epithelialization after 5–7 days was significantly better for the experimental treatment (71%) compared to the standard treatment (67%) (p = 0.034, Wilcoxon), whereas the take rates of the grafts were similar. No related adverse events were recorded. Scar quality was evaluated at 3 (n = 33) and 12 (n = 28) months. The POSAS of the observer after 3 and 12 months and of the patient after 12 months were significantly better for the experimental area. Improvements between 12% and 23% (p ≤ 0.010, Wilcoxon) were detected for redness, pigmentation, thickness, relief, and pliability. Melanin index at 3 and 12 months and erythema index at 12 months were closer to normal skin for the experimental treatment than for conventional treatment (p ≤ 0.025 paired samples t-test). Skin elasticity showed significantly higher elasticity (p = 0.030) in the experimental area at 3 months follow-up. We showed a safe application and significant improvements of wound healing and scar quality in burn patients after treatment with ECs versus SSGs only. The relevance of cultured autologous cells in treatment of extensive burns is supported by our current findings.
The management of deep partial-thickness and full-thickness skin defects remains a significant challenge. Particularly with massive defects, the current standard treatment, split-thickness skin ...grafting, is fraught with donor-site limitations and unsatisfactory long-term outcomes. A novel, autologous, bioengineered skin substitute was developed to address this problem.
To determine whether this skin substitute could safely provide permanent defect coverage, a phase I clinical trial was performed at the University Children's Hospital Zurich. Ten pediatric patients with acute or elective deep partial- or full-thickness skin defects were included. Skin grafts of 49 cm were bioengineered using autologous keratinocytes and fibroblasts isolated from a patient's small skin biopsy specimen (4 cm), incorporated in a collagen hydrogel.
Graft take, epithelialization, infection, adverse events, skin quality, and histology were analyzed. Median graft take at 21 days postoperatively was 78 percent (range, 0 to 100 percent). Healed skin substitutes were stable and skin quality was nearly normal. There were four cases of hematoma leading to partial graft loss. Histology at 3 months revealed a well-stratified epidermis and a dermal compartment comparable to native skin. Mean follow-up duration was 15 months.
In the first clinical application of this novel skin substitute, safe coverage of skin defects was achieved. Safety and efficacy phase II trials comparing the novel skin substitute to split-thickness skin grafts are ongoing.
Therapeutic, IV.
Introduction
Thermal injury often leads to prolonged and excessive inflammation, which hinders the recovery of patients. There is a notable absence of suitable animal-free models for investigating ...the inflammatory processes following burn injuries, thereby impeding the development of more effective therapies to improve burn wound healing in patients.
Methods
In this study, we established a human full skin equivalent (FSE) burn wound model and incorporated human peripheral blood-derived monocytes and T cells.
Results
Upon infiltration into the FSEs, the monocytes differentiated into macrophages within a span of 7 days. Burn-injured FSEs exhibited macrophages with increased expression of HLA-DR
+
and elevated production of IL-8 (CXCL8), in comparison to uninjured FSEs. Among the T cells that actively migrated into the FSEs, the majority were CD4
+
and CD25
+
. These T cells demonstrated augmented expression of markers associated with regulatory T cell, Th1, or Th17 activity, which coincided with significant heightened cytokine production, including IFN-γ, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IP-10 (CXCL10), and TGF-β1. Burn injury did not impact the studied effector T cell subsets or cytokine levels.
Discussion
Collectively, this study represents a significant advancement in the development of an immunocompetent human skin model, specifically tailored for investigating burn-induced innate or adaptive immune reactions at the site of burn injury.
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