Wound healing and hyper-hydration - a counter intuitive model

Winters seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter-intuitive model ‘hyper-hydration’ of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration

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

Accurate assessment of burn severity is critical for wound care and the course of treatment. Delays in classification translate to delays in burn management, increasing the risk of scarring and infection. To this end, numerous imaging techniques have been used to examine tissue properties to infer burn severity. Spatial frequency-domain imaging (SFDI) has also been used to characterize burns based on the relationships between histologic observations and changes in tissue properties. Recently, machine learning has been used to classify burns by combining optical features from multispectral or hyperspectral imaging. Rather than employ models of light propagation to deduce tissue optical properties, we investigated the feasibility of using SFDI reflectance data at multiple spatial frequencies, with a support vector machine (SVM) classifier, to predict severity in a porcine model of graded burns. Calibrated reflectance images were collected using SFDI at eight wavelengths (471 to 851 nm) and five spatial frequencies (0 to 0.2  mm  -  1). Three models were built from subsets of this initial dataset. The first subset included data taken at all wavelengths with the planar (0  mm  -  1) spatial frequency, the second comprised data at all wavelengths and spatial frequencies, and the third used all collected data at values relative to unburned tissue. These data subsets were used to train and test cubic SVM models, and compared against burn status 28 days after injury. Model accuracy was established through leave-one-out cross-validation testing. The model based on images obtained at all wavelengths and spatial frequencies predicted burn severity at 24 h with 92.5% accuracy. The model composed of all values relative to unburned skin was 94.4% accurate. By comparison, the model that employed only planar illumination was 88.8% accurate. This investigation suggests that the combination of SFDI with machine learning has potential for accurately predicting burn severity

The Importance of Hydration in Wound Healing: Reinvigorating the clinical perspective

Balancing skin hydration levels is important as any disruption in skin integrity will result in disturbance of the dermal water balance. The discovery that a moist wound healing environment actively supports the healing response when compared to a dry environment highlights the importance of water and good hydration levels for optimal wound healing. The benefits of “wet” or “hyper-hydrated” wound healing appears to offer benefits that are similar to those offered by moist wound healing over wounds healing in a dry environment. This suggests that the presence of free water itself during wound healing may not be detrimental to healing but that any adverse effects of wound fluid on tissues is more likely related to the biological components contained within chronic wound exudate (e.g. elevated protease levels). Appropriate dressings applied to wounds must be able to absorb not only the exudate but also retain this excess fluid together with its protease solutes while concurrently preventing desiccation. This is particularly important in the case of chronic wounds where peri-wound skin barrier properties are compromised and there is increased permeation across the injured skin barrier. This review discusses the importance of appropriate levels of hydration in skin with a particular focus on the need for optimal hydration levels for effective healing

Comparison of porcine thorax to gelatine blocks for wound

Published online first in International Journal of Legal Medicine. The support of EPSRC and The Home Office are recognised. Open Access, this article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:/ /creativecommons.org/licenses/by/4.0/)Tissue simulants are typically used in ballistic testing as substitutes for biological tissues. Many simulants have been used, with gelatine amongst the most common. While two concentrations of gelatine (10 and 20 %) have been used extensively, no agreed standard exists for the preparation of either. Comparison of ballistic damage produced in both concentrations is lacking. The damage produced in gelatine is also questioned, with regards to what it would mean for specific areas of living tissue. The aim of the work discussed in this paper was to consider how damage caused by selected pistol and rifle ammunition varied in different simulants. Damage to gelatine blocks 10 and 20 % in concentration were tested with 9 mm Luger (9 × 19 full metal jacket; FMJ) rounds, while damage produced by .223 Remington (5.56 × 45 Federal Premium® Tactical® Bonded®) rounds to porcine thorax sections (skin, underlying tissue, ribs, lungs, ribs, underlying tissue, skin; backed by a block of 10 % gelatine) were compared to 10 and 20 % gelatine blocks. Results from the .223 Remington rifle round, which is one that typically expands on impact, revealed depths of penetration in the thorax arrangement were significantly different to 20 % gelatine, but not 10 % gelatine. The level of damage produced in the simulated thoraxes was smaller in scale to that witnessed in both gelatine concentrations,though greater debris was produced in the thoraxes.The support of EPSRC and The Home Office are recognised

Evaluation of Drug Delivery and Efficacy of Ciprofloxacin-Loaded Povidone Foils and Nanofiber Mats in a Wound-Infection Model Based on Ex Vivo Human Skin

Topical treatment of wound infections is often a challenge due to limited drug availability at the site of infection. Topical drug delivery is an attractive option for reducing systemic side effects, provided that a more selective and sustained local drug delivery is achieved. In this study, a poorly water-soluble antibiotic, ciprofloxacin, was loaded on polyvinylpyrrolidone (PVP)-based foils and nanofiber mats using acetic acid as a solubilizer. Drug delivery kinetics, local toxicity, and antimicrobial activity were tested on an ex vivo wound model based on full-thickness human skin. Wounds of 5 mm in diameter were created on 1.5 × 1.5 cm skin blocks and treated with the investigated materials. While nanofiber mats reached the highest amount of delivered drug after 6 h, foils rapidly achieved a maximum drug concentration and maintained it over 24 h. The treatment had no effect on the overall skin metabolic activity but influenced the wound healing process, as observed using histological analysis. Both delivery systems were efficient in preventing the growth of Pseudomonas aeruginosa biofilms in ex vivo human skin. Interestingly, foils loaded with 500 µg of ciprofloxacin accomplished the complete eradication of biofilm infections with 1 × 109 bacteria/wound. We conclude that antimicrobial-loaded resorbable PVP foils and nanofiber mats are promising delivery systems for the prevention or topical treatment of infected wounds

The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

PURPOSE: The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model. MATERIALS AND METHODS: An area of approximately 3 cm2 was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of 14C-GD (300 µg kg-1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2 g application of WoundStat™ 30 s after GD challenge. The decontamination efficacy of WoundStat™ against GD was measured by the direct quantification of the distribution of 14C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements. RESULTS: WoundStat™ sequestered approximately 70% of the applied 14C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15 min post WoundStat™ treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat™ treated animals survived the study duration. CONCLUSIONS: The current study has shown that the use of WoundStat™ as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat™ in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.Peer reviewedFinal Accepted Versio

Further studies of the efficacy of military, commercial and novel skin decontaminants against the chemical warfare agents sulphur mustard, soman and VX

Background/Aims: Following an incident involving toxic chemicals, deployment of countermeasures before the arrival of specialised services at the scene may provide a “therapeutic” window in which to mitigate skin absorption. Methods: Five potential candidates (itaconic acid, N,N′-methylenebisacrylamide, 2-trifluoromethylacrylic acid, fuller's earth and Fast-Act®) previously found effective against a simulant (methyl salicylate) were evaluated against a 10 μL droplet of 14C-sulphur mustard (HD), soman (GD) or VX applied to the surface of porcine skin mounted on static skin diffusion cells. Results: All the decontaminants applied to the skin 5 min post exposure achieved a marked reduction in the amount of 14C contaminant remaining within the skin at 24 h. Itaconic acid significantly (p <.05) reduced the amount of 14C-HD, GD and VX remaining in the skin at 24 h. Additionally, 2-trifluoromethylacrylic acid significantly reduced the amount of 14C-HD, whilst fuller's earth significantly reduced the amounts of 14C-HD and VX recovered within the skin at 24 h. Conclusion: All of the products evaluated in this study performed well in reducing the dermal absorption of all the chemical warfare agents tested.Peer reviewe

Development of a dermal matrix from glycerol preserved allogeneic skin

Dermal substitutes can be used to improve the wound healing of deep burns when placed underneath expanded, thin autologous skin grafts. Such dermal matrix material can be derived from xenogeneic or human tissue. Antigenic structures, such as cells and hairs must be removed to avoid adverse inflammatory response after implantation. In this study, a cost-effective method using low concentrations of NaOH for the de-cellularization of human donor skin preserved in 85% glycerol is described. The donor skin was incubated into NaOH for different time periods; 2, 4, 6 or 8 weeks. These dermal matrix prototypes were analyzed using standard histology techniques. Functional tests were performed in a rat subcutaneous implant model and in a porcine transplantation model; the prototypes were placed in full thickness excision wounds covered with autologous skin grafts. An incubation period of 6 weeks was most optimal, longer periods caused damage to the collagen fibers. Elastin fibers were well preserved. All prototypes showed intact biocompatibility in the rat model by the presence of ingrowing blood vessels and fibroblasts at 4 weeks after implantation. An inflammatory response was observed in the prototypes that were treated for only 2 or 4 weeks with NaOH. The prototypes treated with 6 or 8 weeks NaOH were capable to reduce wound contraction in the porcine model. In neo-dermis of these wounds, elastin fibers derived from the prototype could be observed at 8 weeks after operation, surrounded by more random orientated collagen fibers. Thus, using this effective low cost method, a dermal matrix can be obtained from human donor skin. Further clinical studies will be performed to test this material for dermal substitution in deep (burn) wounds

Bacterial Growth Kinetics under a Novel Flexible Methacrylate Dressing Serving as a Drug Delivery Vehicle for Antiseptics

A flexible methacrylate powder dressing (Altrazeal®) transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth kinetics in combination with three antiseptics was investigated in an in vitro porcine wound model. Standardized in vitro wounds were contaminated with Staphylococcus aureus (MRSA; ATCC 33591) and divided into six groups: no dressing (negative control), methacrylate dressing alone, and combinations with application of 0.02% Polyhexamethylene Biguanide (PHMB), 0.4% PHMB, 0.1% PHMB + 0.1% betaine, 7.7 mg/mL Povidone-iodine (PVP-iodine), and 0.1% Octenidine-dihydrochloride (OCT) + 2% phenoxyethanol. Bacterial load per gram tissue was measured over five days. The highest reduction was observed with PVP-iodine at 24 h to log10 1.43 cfu/g, followed by OCT at 48 h to log10 2.41 cfu/g. Whilst 0.02% PHMB resulted in a stable bacterial load over 120 h to log10 4.00 cfu/g over 120 h, 0.1% PHMB + 0.1% betaine inhibited growth during the first 48 h, with slightly increasing bacterial numbers up to log10 5.38 cfu/g at 120 h. These results indicate that this flexible methacrylate dressing can be loaded with various antiseptics serving as drug delivery system. Depending on the selected combination, an individually shaped and controlled antibacterial effect may be achieved using the same type of wound dressing