BACKGROUND: Incontinence-associated dermatitis (IAD) is one of the most common complications of incontinence. Improved diaper designs can minimize the occurrence of IAD. PURPOSE: To develop a novel diaper design to minimize the damaging effects of incontinence on the epidermal barrier. METHODS: An optimized diaper design was tested for surface dryness (ie, rewet), maintenance of a skin-adapted surface pH of 5.5, and ability to protect epidermal barrier function from an alkaline pH 10.7 challenge. RESULTS: The diapers released a mean (standard deviation [SD]) of 1.2 (0.2) mg/cm2 of solution under pressure after the first loading and a mean of 2.9 (1.7) mg/cm2 after the second loading. The surface pH remained between 4.5 and 5.5 over 5 hours. In healthy skin, transepidermal water loss (TEWL) increased by a mean of 3.43 (4.67) g/m2/h after the alkaline urine solution challenge with the new diaper design versus a mean of 8.38 (5.67) g/m2/h with a cellulose patch (P < .001) as a control. The mean erythema readings were 1.18 (1.30) g/m2/h for the new design and 2.56 (1.25) g/m2/h for the cellulose patches (P < .001). CONCLUSION: The new diaper design minimizes rewetting, maintains an acidic surface, and protects the epidermal barrier against an alkaline pH challenge. This design may help prevent IAD.

The authors have withdrawn their manuscript whilst they perform additional analyses to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author (uadk@dtu.dk).

The authors declare no conflicts of interest.

Objective: The purpose of this review was to identify prognostic models for clinical application in patients with venous leg ulcers (VLUs).Methods: Literature searches were conducted in Embase, Medline, Cochrane, and CINAHL databases from inception to December 22, 2021. Eligible studies reported prognostic models aimed at developing, validating, and adjusting multi -variable prognostic models that include multiple prognostic factors combined, and that predicted clinical outcomes. Methodological quality was assessed using the CHARMS checklist and PROBAST short form questionnaire.Results: Thirteen studies were identified, of which three were validation studies of previously published models, four reported derivation and validation of models, and the remainder reported derivation models only. There was substantial heterogeneity in the model characteristics, including 11 studies focused on wound healing outcomes reporting 91 different predictors. Three studies shared similar predicted outcomes, follow-up timepoint and used a Cox proportional hazards model. However, these models reported different predictor selection methods and different predictors and it was therefore not feasible to summarize performance, such as discriminative ability.Conclusions: There are no standout risk prediction models in the literature with promising clinical application for pa-tients with VLUs. Future research should focus on developing and validating high-performing models in wider VLU populations. (J Vasc Surg Venous Lymphat Disord 2024;12:101673.)

Venous leg ulcers represent a clinical challenge and impair the quality of life of patients. This study examines impaired wound healing in venous leg ulcers at the molecular level. Protein expression patterns for biomarkers were analysed in venous leg ulcer wound fluids from 57 patients treated with a protease-modulating polyacrylate wound dressing for 12 weeks, and compared with exudates from 10 acute split-thickness wounds. Wound healing improved in the venous leg ulcer wounds: 61.4% of the 57 patients with venous leg ulcer achieved a relative wound area reduction of ≥ 40%, and 50.9% of the total 57 patients achieved a relative wound area reduction of ≥ 60%. Within the first 14 days, abundances of S100A8, S100A9, neutrophil elastase, matrix metalloproteinase-2, and fibronectin in venous leg ulcer exudates decreased significantly and remained stable, yet higher than in acute wounds. Interleukin-1β, tumour necrosis factor alpha, and matrix metalloproteinase-9 abundance ranges were similar in venous leg ulcers and acute wound fluids. Collagen (I) α1 abundance was higher in venous leg ulcer wound fluids and was not significantly regulated. Overall, significant biomarker changes occurred in the first 14 days before a clinically robust healing response in the venous leg ulcer cohort.

Background: In vitro skin permeation experiments are highly relevant for pharmaceutical, cosmetic, agricultural developments, and regulatory evaluation. A key requirement is the skin barrier integrity, that is accompanied by an intact stratum corneum (SC) which implements high skin quality. A variety of integrity tests are currently available, for example, measurement of transepidermal water loss, monitoring the permeation of tritiated water and the measurement of transdermal electrical resistance (TER). Materials and Methods: We aimed for a non-destructive examination of barrier integrity as quality control system, based on TER. Therefore, the in-house developed instrument SkinTER measures electrical resistance on excised human skin samples in a non-invasive and easy-to-use pattern. In this proof of concept study, we compared three human in vitro skin models with focus on their TER and permeation properties. The skin integrity was impaired to mimic conditions of skin during age, lifestyle (eg, shaving) or diseases (eg, obesity, psoriasis, and atopic dermatitis). The OECD permeation marker caffeine was correlated to the corresponding TER value. Results: A correlation between both was obtained by having a Pearson coefficient of -0.830. Hereby, a minimum TER value for intact skin samples of similar to 1.77 k Omega*cm(2) was suggested. Intact samples are significantly different (alpha = <= 0.05) to their impaired counterparts in flux and TER values. Conclusion: The new SkinTER instrument gives a quick and non-invasive feedback on skin quality before a permeation experiment.

Objective:To determine the cost-effectiveness/utility of a superabsorbent wound dressing (Zetuvit Plus Silicone) versus the current standard of care (SoC) dressings, from the NHS perspective in England, in patients with moderate-to-high exudating leg ulcers.Method:A model-based economic evaluation was conducted to analyse the cost-effectiveness/utility of a new intervention. We used a microsimulation state-transition model with a time horizon of six months and a cycle length of one week. The model uses a combination of incidence base and risk prediction approach to inform transition probabilities. All clinical efficiency, health-related quality of life (HRQoL), cost and resource use inputs were informed by conducting a systematic review of UK specific literature.Results:Treatment with the superabsorbent dressing leads to a total expected cost per patient for a six month period of £2887, associated with 15.933 expected quality adjusted life weeks and 10.9% healing rate. When treated with SoC, the total expected cost per patient for a six month period is £3109, 15.852 expected quality adjusted life weeks and 8% healing rate. Therefore, the superabsorbent dressing leads to an increase in quality-adjusted life weeks, an increase in healing rate by 2.9% and a cost-saving of £222 per single average patient over six months. Results of several scenario analyses, one-way deterministic sensitivity analysis, and probabilistic sensitivity analysis confirmed the robustness of base-case results. The probabilistic analysis confirmed that, in any combination of variable values, the superabsorbent dressing leads to cost saving results.Conclusion:According to the model prediction, the superabsorbent dressing leads to an increase in health benefits and a decrease in associated costs of treatment.

OBJECTIVE This study assesses a novel dressing concept in venous leg ulcer (VLU) patients. It is based on boosting endogenous growth factor activities synthesised by functional granulation tissue. METHODS Patients received treatment for eight weeks with a hydrated polyurethane-containing foam dressing plus concomitant compression therapy. Wound area reduction (WAR), percentage of wounds achieving a relative WAR of ≥40% and ≥60%, wound pain ratings for the last 24 hours and at dressing changes, EQ-5D Quality of Life questionnaire data, dressing handling and safety parameters were recorded. RESULTS There were 128 patients who received treatment and data for 123 wound treatment courses were documented. Wound area size decreased from 13.3±9.8cm2 to 10.5±12.2cm2 at week eight and median relative WAR was 48.8%. At week eight, a relative WAR ≥40% was reached by 54.5% of the wounds, 41.5% reached a relative WAR of ≥60% and complete healing was observed in 13.5% of wounds. Median wound pain ratings (last 24 hours before dressing change) declined significantly from 30 to 15.5 (100 visual analogue scale [VAS], p=0.0001) and pain at dressing changes from 30 to 12.5 (p≤0.0001). The EQ-5D VAS rating increased from 58.4±19.2mm to 63.1±19.1mm (p=0.0059). CONCLUSION This clinical assessment shows that the concept of boosting endogenous growth factors through hydrated polyurethanes has the potential to accelerate WAR in VLU patients while decreasing pain levels and improving quality of life parameters.

Jacek Mikosiński,1 MD, PhD; Marek Kotala,2 PhD; Markus Stücker,3 MD, Professor of Dermatology, Chief Physician; Krystyna Twardowska-Saucha,4 MD, PhD; Bernd Bonnekoh,5 MD, Professor of Dermatology, Vice-Chairman; Konrad Pańczak,6 MD; Tomasz Aleksiejew-Kleszczyński,7 MD; Joachim Dissemond,8 MD, Professor of Dermatology; Sabine A. Eming,9 MD, Professor of Dermatology; Daniela Kaspar,10 PhD, Senior Manager Clinical Application Studies; Anne Rousseau,11 PhD, Principal Biostatistician; Johanna Bewert,11 PhD, Senior Statistician; Wiebke Schröder,10 PhD, Manager Clinical Application Studies; *Hans Smola,9,10 MD, Professor of Dermatology, Medical Director; the BOOST-CLOSURE Study Group

This review highlights epithelialisation and therapeutic options to optimise and speed the epithelialisation process. To influence this process therapeutically, it is important for clinicians to understand the underlying principles of epithelialisation. The role of growth factors and the hostile local wound environment can explain why epithelial wound closure is so difficult to speed up in some chronic wounds. Clinicians should be aware of the different surgical techniques of skin grafting and more advanced technologies, such as skin substitutes, as options for wounds which fail to respond to standard protocols. Finally, novel dressing-based concepts are discussed, including macromolecular crowding, a concept which aims at boosting growth factor activities produced in the wound space once wound healing is normalised and underway.

Infected wounds are a major problem for patients and health care systems. The inflammation triggers expression of high levels of extracellular protease activities which degrade newly formed granula...

Infected wounds are a major problem for patients and health care systems. The inflammation triggers expression of high levels of extracellular protease activities which degrade newly formed granulation tissue. The expression of host-derived proteases had been studied in wound healing extensively. In contrast, the contribution of bacterial proteases in impaired healing acute and chronic wounds is poorly understood as is how bacterial proteases can be blocked. In this study the expression of P. aeruginosa proteases was studied. P. aeruginosa is associated with poor healing and sufficiently common in wound infections to merit closer study. We used in vitro biofilm and planktonic culture models to analyze the culture-dependent expression of different P. aeruginosa proteases and how protease modulating polymers can inhibit activities. P. aeruginosa (PAO1, DSM 22644) was grown in LB o medium (aerated planktonic cultures) or in a biofilm culture model (dialysis tubing on LB o plates). The supernatant of planktonic or wash fluids from biofilm cultures were analyzed for protease activity. Global extracellular protease activities increased in a time- and culture condition-dependent manner (for planktonic cultures 180 ng/ml trypsin equivalent 8h, 330 ng/ml 24h, 490 ng/ml 48h; biofilm cultures 190 ng/ml trypsin equivalent 8h, 420 ng/ml 24h, 170 ng/ml 48h). Enzyme zymography revealed in biofilm cultures predominant bands at 50 kD (8h, 24h, 48h), 90 kD (24h) and > 200 kD (8h, 24h, 48h). In planktonic cultures the pattern was different 50 kD (8h), 90 kD (8h, 24h, 48h), 130 kD (24h, 48h) and > 200 kD (8h, 24h). Two different polyacrylate superabsorbers could inhibit P. aeruginosa protease activities. Favor PAC 300 blocked protease activity by 60% and SXM 9170 by 35%. These data demonstrate complex, culture-dependent expression of extracellular proteases in P. aeruginosa, a microorganism associated with poor wound healing outcomes. From a therapeutic perspective polyacrylate superabsorbers strongly inhibited global protease activities. In the next steps the protease expression pattern needs to be analyzed in P. aeruginosa wounds and correlated with healing progression.

Due to the specific pathophysiological state of tissues in the chronic wounds and frequent limitations on the part of the patient the complex treatment of such wounds or wound debridement becomes quite a complicated therapeutic task. Due to HydroClean dressings that without any active components are fit for any patients and by this simplify and increase the quality of the wound debridement surgeons received modern unique hydroactive wound dressings for effective local therapy of chronic wounds of various etiology.

Impaired cutaneous wound healing is a major complication in elderly people and patients suffering from diabetes, the rate of which is rising in industrialized countries. Heterogeneity of clinical manifestations hampers effective molecular diagnostics and decisions for appropriate therapeutic regimens. Using a customized positional quantitative proteomics workflow, we have established a time-resolved proteome and N-terminome resource from wound exudates in a clinically relevant pig wound model that we exploited as a robust template to interpret a heterogeneous dataset from patients undergoing the same wound treatment. With zyxin, IQGA1, and HtrA1, this analysis and validation by targeted proteomics identified differential abundances and proteolytic processing of proteins of epidermal and dermal origin as prospective biomarker candidates for assessment of critical turning points in wound progression. Thus, we show the possibility of using a fine-tuned animal wound model to bridge the translational gap as a prerequisite for future extended clinical studies with large cohorts of individuals affected by healing impairments. Data are available via ProteomeXchange with identifier PXD006674.

Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions. We provide evidence that CCAAT/enhancer-binding protein α (C/EBPα), a differentiation-regulating transcription factor and suppressor of UV-induced skin carcinogenesis, directly binds the miR-203 gene within its hairpin region and thereby induces miR-203 transcription. Our data further demonstrate that the HPV8 E6 protein significantly suppresses this novel C/EBPα/mir-203-pathway. As a consequence, the miR-203 target ΔNp63α, a proliferation-inducing transcription factor, is up-regulated, while the differentiation factor involucrin is suppressed. HPV8 E6 specifically down-regulates C/EBPα but not C/EBPβ expression at the transcriptional level. As shown in knock-down experiments, C/EBPα is regulated by the acetyltransferase p300, a well-described target of cutaneous E6 proteins. Notably, p300 bound significantly less to the C/EBPα regulatory region in HPV8 E6 expressing keratinocytes than in control cells as demonstrated by chromatin immunoprecipitation. In situ analysis confirmed congruent suprabasal expression patterns of C/EBPα and miR-203 in non-lesional skin of EV-patients. In HPV8-positive EV-lesions both factors are potently down-regulated in vivo further supporting our in vitro data. In conclusion our study has unraveled a novel p300/C/EBPα/mir-203-dependent mechanism, by which the cutaneous HPV8 E6 protein may expand p63-positive cells in the epidermis of EV-patients and disturbs fundamental keratinocyte functions. This may drive HPV-mediated pathogenesis and may potentially also pave the way for skin carcinogenesis in EV-patients.

Chronic wounds are a major clinical problem for patients and health care systems. Excessive protease activities in the wound are associated with impaired healing. The role of bacterial proteases in chronic wounds is poorly understood. We tested whether protease modulating polymers (polyacrylate superabsorber) can inhibit bacterial protease activities. For a start we studied expression of P. aeruginosa proteases in an in vitro biofilm and planktonic culture model. We tested whether protease modulating polymers (polyacrylate superabsorber) can inhibit protease activities. P. aeruginosa (PAO1, DSM 22644) was grown in LBo medium (aerated planktonic cultures) or in the biofilm culture model (on dialysis tubing on LBo plates). Supernatants of planktonic or wash fluids from the biofilm cultures were analyzed for protease activity. The biofilm phenotype was confirmed by presence of large amounts of extracellular genomic DNA (> 48 kb). Global extracellular protease activities increased in a time- and culture condition-dependent manner (planktonic cultures: 180 ng/ml trypsin equivalent 8h, 330 ng/ml 24h, 490 ng/ml 48h; biofilm cultures 190 ng/ml trypsin equivalent 8h, 420 ng/ml 24h, 170 ng/ml 48h). Enzyme zymography revealed that in biofilm cultures the predominant bands were 50 kD (8h, 24h, 48h), 90 kD (24h) and > 200 kD (8h, 24h, 48h). In planktonic cultures the pattern was different 50 kD (8h), 90 kD (8h, 24h, 48h), 130 kD (24h, 48h) and > 200 kD (8h, 24h). P. aeruginosa protease activity could be blocked by two different polyacrylate superabsorbers. Favor PAC 300 blocked protease activity by 60% and SXM 9170 by 35%. These data demonstrate complex, culture-dependent production of extracellular proteases in P. aeruginosa, associated with poor wound healing outcomes in colonized wounds. From a therapeutic perspective polyacrylate superabsorbers strongly inhibited global protease activities. In the next steps the protease expression pattern needs to be analyzed in P. aeruginosa wounds and correlated with healing outcomes when blocked with polyacrylate superabsorber-containing dressings.

Objective: To assess the cost-effectiveness of a polyacrylate (PA)-based hydrogel compared to an amorphous hydrogel in wound bed preparation for venous leg ulcers.Method: A cost-effectiveness analysis was undertaken alongside a multicenter, randomized controlled trial performed in France. A total of 75 patients with venous leg ulcers extensively covered with fibrin and necrotic tissue were randomized to a PA-containing hydrogel or an amorphous hydrogel. Wounds were treated for 14 days and costs were estimated from the - German payer's perspective. Medical costs included study treatment, wound treatment - supply, and labor time. The clinical benefit was expressed as the number of patients with wounds.50% covered with granulation tissue within 14 days. The incremental cost-effectiveness ratio (ICER) was expressed as the additional cost spent with >50% granulation tissue per day per patient within 14 days of leg ulcer care.Results: Because of individual pricing of wound dressings in hospitals, cost data were derived from the outpatient sector. A total of 33 patients were treated using the PA-based hydrogel and 37 patients using the amorphous hydrogel. The estimated total direct costs per patient and per 14 days of therapy were (SIC)306 for both treatment groups. However, with the PA-based hydrogel, 2.5 additional days with wounds covered.50% with granulation tissues were gained within 14 days of leg ulcer care compared to the comparator. The ICER was (SIC)0 per additional day spent with >50% granulation tissue.Conclusion: Although there were a greater number of dressing changes in the PA-based hydrogel treatment, the total treatment cost for 14 days of leg ulcer care was the same for both the PA-based-hydrogel and amorphous-hydrogel treatment modalities. The cost benefit favored the PA-based hydrogel because of its greater clinical efficiency in producing a viable wound bed.

The skin provides an essential barrier against the environment and, therefore, every defect in this tissue has to be rapidly and efficiently repaired. In adult mammals, wounding initiates a well-coordinated sequence of events involving blood clotting and inflammation, new tissue formation, and finally tissue remodeling. The result is a new tissue with a functional skin barrier. However, in adult mammals, wound healing results in formation of a scar, which lacks all appendages and has a reduced tensile strength compared to uninjured skin. By contrast, embryonic skin wounds heal without scar formation and some lower organisms are even capable of completely regenerating the injured tissue. Abnormalities in the wound healing response may lead to excessive healing and formation of hypertrophic scars or keloids. At the other extreme, the repair process is often delayed or completely inhibited, resulting in the development of different types of chronic, nonhealing ulcers. This increases the risk of cancer development at the wound site, in particular under conditions of chronic inflammation. Remarkably, there are striking parallels between wound healing and cancer at the molecular and cellular levels, highlighting the importance of understanding the mechanisms underlying normal and impaired wound healing. Here, we summarize the major events of the wound healing process and the clinical problems associated with impaired wound healing.