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Dispersions in transcutol/isopropyl myristate make C60 fullerene molecules suitable for transdermal delivery. We found that C60 can successfully permeate the skin using pig skin in Franz diffusion cells. Molecular dynamics simulations and transmission electron microscopy confirmed these observations. Basic cosmetic formulations with transcutol/ isopropyl myristate without harsh organic solvents show a high potential for delivery of C60 for biopharmaceutical and cosmetics applications., This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI01-0145-FEDER-006684).). Artur Ribeiro thanks FCT for the SFRH\BPD\98388\2013 grant., info:eu-repo/semantics/publishedVersion

An important property of sunscreens is their water resistance after the application on human skin. In this work, the hypothesis that UV absorber molecules which are able to form liposomes, so-called liposomogenic UV absorbers, show better water resistance on a pig skin model than UV-absorbing molecules lacking this ability was tested. The assumption behind is that molecules which can form liposomes are able to integrate into the stratum corneum lipids of the skin. Three different liposomogenic UV absorbers were synthesized and their behavior investigated, leading to the confirmation of the hypothesis. With one of the liposomogenic UV absorbers, it was possible to show the integration of the UV absorber molecules into the bilayers of another liposome consisting of phosphatidylcholine, supporting the assumption that liposomogenic UV absorbers exhibit improved water resistance because they integrate into the skin lipids.

Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics-relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration-depth profile using tape-stripping (measures KSC/v and DSC/HSC2, where HSC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of KSC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures KSC/v and DSC/HSC2, and is based on Fick's laws). KSC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two-fold higher, and all values were within 10-fold of each other. Only indirect determination of KSC/v by Protocol 2B was different from the direct measurement of KSC/v by Protocol 2A and Protocol 1 for 7-EC. The variability of KSC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. DSC/HSC2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, KSC/v, and DSC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd.

Minimally invasive delivery of peptide and protein molecules represents a significant opportunity for product differentiation and value creation versus standard injectable routes of administration. One such technology utilizes microneedle (MN) patches and it has made considerable clinical advances in systemic delivery of potent macromolecules and vaccines. A sub-class of this technology has focused on preparation of solid dense MN arrays followed by precision formulation coating on the tips of the MN. The objective of this study was to develop a drug product using the MN technology that has similar bioperformance when compared to subcutaneous route of delivery and can provide improved stability under storage. Therapeutic peptide (Peptide A, Merck & Co., Inc., Kenilworth, NJ, USA) is being developed as a subcutaneous injection for chronic dosing with a submilligram estimated therapeutic dose. Peptide A has chemical and physical stability challenges in solution and this led to exploration of a viable drug product which could provide therapeutic dosages while overcoming the stability issues seen with the compound. This work focused on developing a coated solid microstructure transdermal system (sMTS) for Peptide A followed by detailed in vitro and preclinical evaluation for two different coating formulations. Based on initial assessment, ~250 μg of Peptide A could be coated with precision on a 1.27cm2 patch which contained 316 MN’s. The delivery from these systems was achieved with absolute bioavailability being similar to the subcutaneous delivery (88% and 74% for coated sMTS 1 & 2 and 75% for subcutaneous delivery). Stability of Peptide A was also found to be significantly improved when coated on the sMTS system with minimal degradation recorded at room temperature storage as compared to the subcutaneous liquid formulation. Additionally, skin irritation (on pig skin) was also measured in this study and it was found to be minimal and self-resolving. This evaluation provided a viable option for developing a drug product with improved stability and successful delivery of the investigated molecule.

Many skin diseases are defined by the presence of neutrophils, which are among the first cells to respond to infection and inflammation. Currently, neutrophil identification in the skin is costly and slow. The objectives of the present work are to investigate the feasibility of detecting the presence of neutrophils in live skin microsamples using chemiluminescence and develop a device and procedures that will enable preclinical and clinical investigations. Our approach consists of collecting skin microsamples and exposing them to reagents that activate neutrophils and amplify the light emission produced by chemiluminescence. Experiments using live pig skin with and without inflammation show that it is feasible to detect the presence of neutrophils in the skin. The proposed method is minimally invasive, simple, fast, and does not require user specialization. The developed system is compact in size with a small footprint, which makes it portable and suitable for point-of-care diagnostics.

Introduction Allogeneic and xenogeneic skin are recognized as the best coverings for skin burn wounds, but currently face a supply shortage. To solve this problem, our research group developed a standardized manufactured hydrogel dressing based on a new type of highly bioactive recombinant human collagen. Study design Prospective self-controlled trial. Objective To evaluate the efficacy and safety of recombinant human collagen hydrogel in the treatment of partial burn wounds to the skin compared to those of xenogeneic skin. Methods This study included twenty-one patients admitted to Shanghai Changhai Hospital within 48 h after receiving partial-thickness skin burns. The wounds were symmetrically separated along the axis and treated with recombinant human collagen hydrogel (RHCH) or a human-CTLA4-Ig gene-transferred pig skin xenotransplant. The condition of the wound surfaces was recorded on days 0 (of enrollment), 5, 10, 15, and 20, and bacterial drug sensitivity testing, hematuria examination, and electrocardiographic tests were conducted on days 0, 10, 20, or on the day of wound healing. Results There were no statistically significant differences in wound healing time between the two groups. The median number of days to healing was 11.00 ± 0.56 for xenogeneic skin vs. 11.00 ± 1.72 for RHCH. Conclusion During the observation period, the therapeutic effect of the RHCH developed by our group on partial-thickness burn wounds was not significantly different from that of gene-transferred xenogeneic skin. Thus, our designed RHCH shows potential for clinical use to treat burn wounds on the skin.

Background Optical coherence tomography (OCT) is a promising imaging modality for skin cancer diagnosis. However, this capability has been hindered by the low contrast between normal and neoplastic tissue. To overcome this limitation, gold nanoparticles have been used to enhance the contrast in OCT images and are topically administered to reduce the risk of systematic side effects associated with intravenous injection. To ensure efficient penetration and distribution of the nanoparticles, an enhanced delivery strategy is required. In this porcine study, we assessed two delivery methods: (a) using dimethyl sulfoxide (DMSO) and (b) via sonophoresis. Materials and methods The gold nanoparticles were topically applied on pig skin before evaluating DMSO and sonophoresis as penetration enhancers in topical administration. The OCT images were taken from the same locations to monitor signal change. Conclusion The combination of DMSO and sonophoresis is an effective method to enhance the penetration and diffusion rate of nanoparticles during topical administration. Significance Topical administration of nanoparticles is advantageous in dermatological applications. Nevertheless, efficient topical delivery remains a challenge. DMSO and sonophoresis can be used as two effective approaches to enhance topical delivery of nanoparticles.

Two versions of an electrically powered device (Rotorinser) to sample carcasses or other surfaces in situ for microbiological analysis and several different sampling protocols were evaluated against excision plus stomaching for ability to remove bacteria from pig skin and beef carcass tissue. Both devices sampled circular areas of approximately 14 cm 2 . Ten tissue samples were used for each set of conditions. Rotorinser bacterial removal efficiency was calculated as R/(R + S), where R is the Rotorinser count (CFU cm -2 ) and S is the count on stomached, excised tissue after rotorinsing. Stomacher efficiencies were calculated as S1/(S1 + S2), where Sl is the first stomacher count of excised tissue and S2 is the count from a second stomaching. Both Rotorinsers were much better than traditional swabs. Rotorinser I gave removal efficiencies of 0.79 to 0.88 for beef, and 0.79 to 0.95 for pork. Prewetting surfaces for 5 min improved removal, but mixtures of enzymes did not. Rotorinser 2 applied with NaCI or NaCI-Tween 80 diluent for either 30 or 60 s was significantly better (0.93 and 0.98) than the stomacher (0.86) at removing aerobic mesophilic bacteria from pork skin. The Rotorinser causes negligible tissue damage and can be used on surfaces at any angle.

Crossbows are ancient distance weapons, which in modern times have been largely replaced by guns. Nowadays, they are used for target shooting and in some countries also for hunting. Bolts/arrows fired from a crossbow have a rather low initial velocity but a high penetration capacity comparable to bullets shot from firearms. A considerable number of homicidal, suicidal, and accidental crossbow injuries have been reported up to the present day both under clinical and medicolegal aspects. A recent suicide case gave rise to a systematic study of entrance wounds from field-tipped arrows with shafts made of carbon. Composite models (ballistic gelatin covered with pig skin) served as targets. As found in the suicide case presented, the roundish entrance wounds were characterized by a slit-like severance of the skin surrounded by a pronounced blackish ring resembling the bullet wipe in gunshots. The material deposited circularly on the margins was subjected to the sodium rhodizonate test, SEM/EDX analysis, histological examination, and Raman spectroscopy. As expected, the elements typical of gunshot residues could not be detected. The element pattern of the black deposits was consistent with that of the arrows' tips and carbon shafts. Histological examination revealed that the carbonaceous material was deposited on the abraded wound margins suggesting a mechanism of friction causing the transfer of material. In conclusion, the presence of a black-margined roundish skin wound does not necessarily mean a bullet wipe. The casuistic part of the paper deals with a suicidal shot to the chest in a 48-year-old man, inflicted with a field-tipped carbon arrow which perforated both the heart and the thoracic aorta. In addition, a review of the literature on fatal crossbow injuries is presented.

Objectives Emergent cricothyroidotomy (EC) is a rarely used yet lifesaving procedure that is important for an emergency physician to master throughout his or her training. We evaluated the difference in utilization of a manikin or porcine model among emergency medicine (EM) residents when teaching EC. We also evaluated the difference in the models using two different commonly utilized and taught techniques: "scalpel-finger-bougie" (SFB) technique and the Melker technique (MT). Methods This was a prospective crossover design. Instructions about the procedure were provided; study participants were randomly assigned to one of two groups and performed cricothyrotomy on both manikin and porcine simulators using both the Melker and the SFB techniques. Each group was started with the technique on the second simulator opposite what they started with on the first simulator. After the procedures, study participants completed a questionnaire that used the same format for both groups. All survey questions required a 7-point Likert scale response. Confidence, difficulty, reality of the anatomy, and landmarks were compared. Results Fifteen EM residents participated in the study. Compared to the porcine-first group, the manikin-first group rated the anatomy more realistic (question 5) after their first attempt (6.29 vs. 5.87) than their second attempt (using the porcine model; 4.29 vs. 5.62; main effect for attempts [first vs. second] p = 0.027; interaction p = 0.074). Interestingly, the porcine model-first group rated the landmarks (question 6) significantly easier to find in both attempts (6.87 vs. 5.86 on the first attempt and 6.50 vs. 5.57 on the second attempt; p = 0.012). Twelve participants (80%) chose SFB as their preferred technique to use in real-life scenario. Conclusion The Manikin model tends to be more realistic in cricothyrotomy simulation than the porcine model. The influence of fresh pig skin overlying the porcine model may require further research. Landmark identification during the procedure was easier on both models when participants start with the porcine model. Participants prefer the SFB over MT if faced with a real-life scenario.

The purpose of this work has been to determine differences in biomechanical properties of porcine skin from organic and non-organic farming as porcine skin is widely used as a model for human skin. A test apparatus was used, using gravity to stretch and finally tear a dumbbell-shaped specimen of prepared abdominal skin with a testing surface area of 25 × 4 mm. A total of 32 specimens were taken from seven individual pigs, three from organic and four from non-organic farming, in different orientations with respect to the Langer’s lines. The tests were performed at a dynamic speed of around 1.66 m/s (corresponding to a nominal strain rate of 67 s−1). Engineering strain at rupture was higher in pig skin from non-organic farming with values up to 321% as opposed to 90% in organic pig skin. The maximum tensile stress found in non-organic pig skin was lower than in pig skin from organic farming with maximum values of 34 MPa as opposed to 58 MPa. The reason for the difference in biomechanical properties is unclear; the effect of sunlight is discussed as well as other factors like age and exercise. It seems that the biomechanical properties of porcine skin from organic farming are more similar to those of human skin.

Electroencephalogram (EEG) systems commonly used in laboratory environments are rapidly moving towards real-world applications. In this paradigm shift, new methods for recording and classifying EEG signals are necessary. However, it is challenging to validate the efficacy of new electrodes or other data acquisition components when the target signal cannot be controlled. Here, we propose and validate a method for using an attenuated tACS unit to generate a ground-truth signal in conjunction with porcine skin to determine electrode effectiveness. We highlight the utility of this approach by objectively comparing the signal quality of a chirp signal though porcine skin as measured by four different EEG electrodes, three "dry" and a standard hydrogel. We believe a similar approach could be used with transdermal signals on live humans to observe effects of motion, electrode type, or environment on EEG in order to improve design for use in noisy, non-laboratory settings.

Gelatin is one of the most widely used food ingredients. Its applications in food industries are very broad including enhancing the elasticity, consistency and stability of food products. Gelatin is also used as a stabilizer, particularly in dairy products and as a fat substitute that can be used to reduce the energy content of food without negative effects on the taste. Besides the food industry, gelatin is also useful in medicine, pharmaceutical and photographic industries. Gelatin is a valuable protein derived from animal byproducts obtained through partial hydrolysis of collagen originated from cartilages, bones, tendons and skins of animals. It is a translucent brittle solid substance, colourless or slightly yellow, nearly tasteless and odourless. Most commercial gelatin is currently sourced from beef bone, hide, pigskin and, more recently, pig bone. It was reported that 41% of the gelatin produced in the world is sourced from pig skin, 28.5% from bovine hides and 29.5% from bovine bones. This paper reviews the potential of plant-based products as halal substitutes for gelatin.

Liquid nanovehicles are gaining interest in drug delivery because of the high solubilization capacity of bioactives at their interface and enhanced permeation of compounds across physiological membranes. However, the dermal application of liquid nanovehicles is still limited. The goal of this research is to develop a dermal delivery system based on embedding of liquid nanovehicles into polymeric films, which will allow controlled release of the nanodroplets with the solubilized drug. In this study, we describe the incorporation of empty and curcumin-loaded nanodomains into polymeric film. The novel technology results in formation of homogeneous, transparent and elastic films with high (up to 85 wt%) loading capacity of nanodomains. The fundamental structural characterizations show that nanodomain structures embedded in the dry film are spontaneously reformed during the dermal application with similar droplets size of 10 nm. Ex-vivo release studies were performed on Franz diffusion cells and demonstrated a significant permeation of curcumin through the pig skin. This novel film technology can serve as a "solid platform reservoir" for liquid nanovehicles which enables controlled release of nanodroplets with solubilized bioactive.

International audience; The Covid-19 coronavirus, SARS-CoV-2, is inactivated much faster on paper (3 h) than on plastic (7 d). By classifying materials according to virus stability on their surface, the following list is obtained (from long to short stability): polypropylene (mask), plastic, glass, stainless steel, pig skin, cardboard, banknote, cotton, wood, paper, tissue, copper. These observations and other studies suggest that SARS-CoV-2 may be inactivated by dryness on water absorbent porous materials but sheltered by long-persisting micro-droplets of water on waterproof surfaces. If such physical phenomenons were confirmed by direct evidence, the persistence of the virus on any surface could be predicted, and new porous objects could be designed to eliminate the virus faster.

This study evaluated effects of swelled pig skin (SPS) with various natural vinegars (Bokbunja, brown rice, cider, and lemon vinegars) on the quality of the Korean traditional blood sausages. Adding SPS with various natural vinegars resulted in increased moisture content, cooking loss, L* values, and a* values and decreases in fat, protein content (p

The dietary intake of vitamin D is currently below the recommended intake of 10-20 µg vitamin D/day. Foods with increased content of vitamin D or new products with enhanced vitamin D are warranted. Light-emitting diodes (LEDs) are a potential new resource in food production lines. In the present study the exposure conditions with ultraviolet (UV) LEDs were systematically investigated in the wavelength range 280-340 nm for achieving optimal vitamin D bio-fortification in pig skin. A wavelength of 296 nm was found to be optimal for vitamin D3 production. The maximum dose of 20 kJ/m2 produced 3.5-4 µg vitamin D3/cm2 pig skin. Vitamin D3 produced was independent on the combination of timeand intensity of the LED source. The increased UV exposure by UV-LEDs may be readily implemented in existing food production facilities, without major modifications to the process or processing equipment, for bio-fortifying food products containing pork skin.

“Rambak” crackers are one of the traditional foods consumed among Indonesian people made from various kinds of animal skin. The present study highlights the analysis of lard obtained from extraction of “rambak” crackers using Fourier transform infrared (FTIR) spectroscopy in combination with chemometrics of partial least square and principle component analysis. FTIR spectroscopy at wavenumber regions of 1200–1000 cm–1 was successfully used for quantification and classification of lard in “rambak” crackers. The relationship between actual value of lard and Fourier transform infrared predicted value has R2 value of 0.946 with low errors in calibration and validation models. Furthermore, the chemometrics principle component analysis can be successfully used for determination of pig skin through analysis of lard in commercial “rambak” crackers. The developed method (FTIR spectroscopy coupled with chemometrics) is rapid and reliable for quantification and classification of lard in “rambak” crackers.

In vitro studies of human dermal fibroblast (DF) heterogeneity have long been reported, yet in vivo studies and related research on animals are rare. The objectives of the study were to determine whether the DFs of pigs exhibit heterogeneity and to identify an animal model for the in vivo study of DF heterogeneity. The skin of three female red Duroc pigs (FRDPs) was separated into six layers, and the second and fifth layers (i.e., the superficial and deep dermis) were used in the establishment of wound models and cell cultures. To create the wound models, 54 tongue-shaped flaps were created on one side of the dorsum, and the underlying dermis was then fully replaced with the superficial or deep dermis (the superficial and deep groups, respectively). Skin samples were harvested at postoperative weeks 1, 2, and 3 for measurements of the normal and wounded skin thicknesses. Cells cultured from the superficial and deep dermis (i.e., superficial and deep DFs) were subjected to quantitative estimation of collagen and electron microscopy. The wounded skin thickness in the deep group was significantly greater than that in the superficial group. In contrast with the long deep DFs, the superficial DFs were short and exhibited microvilli-like cell surface projections. Compared with the superficial DFs, the deep DFs exhibited a greater density of rough endoplasmic reticulum and produced significantly more collagen. Similar to humans, FRDPs exhibit DF heterogeneity and should thus be a good animal model for in vivo studies of DF heterogeneity. Anat Rec, 299:1585-1599, 2016. © 2016 Wiley Periodicals, Inc.

Although tattoos have been observed on mummies dated to over 5000 years old, the generally poor preservation of human remains makes it difficult to use this type of adornment to understand how inscriptions on the body have been used to define self and social ascriptions. A potential method for detecting tattooing is to identify the tools used to make the markings. To assist recognition of tattooing tools, an extensive set of experiments was conducted in which retouched obsidian flakes bearing various pigments were used to pierce pig skin. Diagnostic use wear and residues associated with tattooing were identified. To illustrate the value of these results, traces preserved on a highly recognizable class of obsidian retouched artefacts from the Nanggu site (SE-SZ-8) in the Solomon Islands were analysed. Results indicate that these tools were used to pierce skin and may therefore have been tattooing implements involved in social, ritual and/or medical practices.

Auto-sacrificial blood-letting was an important ritual practice for the ancient Maya. Letting blood using implements like sharpened bone, stingray spines, thorny ropes, and obsidian blades provided the Maya the means to petition their ancestors and the gods for rain, good harvests, and success in warfare, among other needs and desires. The prevailing assumption is that obsidian blades recovered from ceremonial or ritual contexts, like caches, burials, and caves, were used for blood-letting. This belief is primarily founded on contextual, epigraphic, iconographic, and ethnohistoric information. With some exceptions, however, this interpretation does not typically include any use-wear analysis of the blades themselves. Reasons for the limited application of use-wear analysis to identify obsidian blood-letters recovered from ceremonial or ritual contexts include observational difficulties associated with the minimal wear development resulting from their short term use in this activity and contact with a soft and yielding medium like human flesh. This paper explores an approach to assist in identifying obsidian blades likely used for auto-sacrificial blood-letting based on high-power microscopic (400 ×) use-wear analysis. The need for this experimental work was initiated by the recovery of some obsidian blades from Actun Uayazba Kab, an ancient Maya cave in Belize, that were suspected blood-letters. Emphasis is placed on the observation and differentiation of wear features produced on 26 experimental obsidian blade segments used to cut pig skin/flesh, as a proxy for human flesh, as well as soft cow hide, fresh pig bone, fresh cohune palm fronds, and queen conch shell. The wear on the suspected blood-letters from Actun Uayazba Kab is similar to that produced on the experimental replicates after very minimal use (30 strokes). Moreover, the combination of wear features on the skin/flesh, hide, bone, plant, and shell can be distinguished from one another even after short-term use.

Biological samples, such as blood, are regularly encountered at violent crime scenes and successful identification is critical for criminal investigations. Blood is one of the most commonly encountered fingerprint contaminants and current identification methods involve presumptive tests or wet chemical enhancement. These are destructive however; can affect subsequent DNA sampling; and do not confirm the presence of blood, meaning they are susceptible to false positives. A novel application of visible wavelength reflectance hyperspectral imaging (HSI) has been used for the non-contact, non-destructive detection and identification of blood stained fingerprints across a range of coloured substrates of varying porosities. The identification of blood was based on the Soret γ band absorption of haemoglobin between 400 nm and 500 nm. Ridge detail was successfully visualised to the third depletion across light coloured substrates and the stain detected to the tenth depletion on both porous and non-porous substrates. A higher resolution setup for blood stained fingerprints on black tiles, detected ridge detail to the third depletion and the stain to the tenth depletion, demonstrating considerable advancements from previous work. Diluted blood stains at 1500 and 1000 fold dilutions for wet and dry stains respectively were also detected on pig skin as a replica for human skin.

To reduce the time required for suture closure for central venous catheterization, a new procedure was developed using a continuous suture technique. The present study was conducted to investigate the usefulness of this method.The study was conducted with 90 volunteers among the doctors in the university hospital. Preliminary training (using video) on the two fixation methods was given to the participants prior to the experiment. After applying the central vein of the pig skin, a suture up to the butterfly seal was prepared, and the participant was allowed to fix the suture using the classic method and the new method. The time required for suturing was measured in seconds, and the tension was determined using a tension measuring device after suturing.When using the new "one-time method," the time required was shortened by about 20.50s on average compared with the conventional method (P0.001). The median and quartile of the tension of the thread for the one-time method was 1.10kg (1.00-1.20kg) and of the conventional method was 1.10kg (1.00-1.20kg), which showed no statistically significant difference between the two groups (P=0.476).We found that the new one-time method provided faster and more convenient central catheterization and catheter securement than the conventional methods.

A woman was stabbed 10 times and killed. The suspect confessed that he had used a thick (0.7 cm), single-edged survival knife with a serrated spine. However, the bilateral ends of the stab wounds appeared sharp. To address this discrepancy, we used pig skin to examine whether the knife could have been used to make the thin stab wounds observed. The widths of the pig skin wounds were approximately half the width of the knife and the ends of some wounds appeared sharp, particularly when the knife was held at a right angle. It was concluded that the suspect could have killed the victim using the survival knife. Similar pig skin experiments could be useful for forensic pathologists to determine whether a weapon of interest might have been used to inflict certain injuries.

In this paper, we develop a 2-dimensional membrane model for the inelastic response of nominally leathery materials applicable to many tissues, particularly skin. These materials, while nominally elastic, show substantial and complex hysteretic response under cyclic loading (usually referred to as the Mullins-type softening). Furthermore, they exhibit both rate dependent behavior and permanent residual strain upon unloading. The proposed model is based on the notion of a multinetwork model composed of a background material and possibly many families of fibers with a superposed response. The rate dependent inelasticity and permanent strain are modeled through fiber slippage. We show the efficacy of the model by comparing with experiments in rat and pig skin under various cyclic loading conditions. The parameters of the modal are reasonably easy to measure directly from experiments. The key ingredients of the fiber part of the response are (1) a simple two-slope elastic response that accounts for the rapid stiffening response of the fibers, with smooth transition between the slack and stiff response representing the fiber recruitment (2) a non affine deformation of the fibers to account for the fiber slippage and recovery (3) a rapidly hardening response to account for the memory of the skin regarding its previous maximum stretched state. The entire framework is written in rate form and is easily implemented with an elementary integration scheme. The model is capable of simulating not only the overall behavior of the skin but internal minor hysteresis as well.

To break the “Black-Box” status of the wound healing process under traditional dressing, which cannot achieve satisfactory repair outcome of skin wounds, a wound healing system with the abilities of pro-regeneration and real-time monitoring of wound status has become a considerable necessity. Here, by integrating the emerging bioelectronics and software, we created a flexible wound healing system. The hardware system was designed as Band-Aid shaped with a double-layer structure; the upper is the flexible temperature-sensing layer comprising the temperature sensor STH21, power manager circuit and data processing circuit, and the lower is a collagen-chitosan dermal equivalent for skin regeneration. A customized software application (app) installed on a smartphone to receive data from the sensing layer by BLE4.0 can display and analyze real-time wound temperature. Our system had high monitoring sensitivity and stability, good stretchability, excellent reliability and biocompatibility. It was applied to a pig skin wound model to reveal temperature fluctuation during the entire wound regeneration process. As a credible reference and foundation for further early warning of an adverse event, three main phases of temperature fluctuation were found: the rising phase (below 39 °C), plateau phase (39–39.5 °C), and falling phase (below 39 °C), which were accompanied by significant wound biological events, including inflammatory cell infiltration, angiogenesis and wound healing. Furthermore, verified by wound infection models of different healing phases and wound Gram's staining, early warning ahead of serious infection was realized with the use of a customized app's alarm.

The skin loses its moisture with advancing age, causing cosmetic issues such as wrinkles. In addition, the loss of moisture leads to hypersensitivity to external stimuli such as UV light. Transcutaneous supplementation with hyaluronic acid (HA) is an effective and safe method of recovering the moisturizing function and elasticity of the skin. However, the transcutaneous delivery of HA remains challenging owing to the barrier function of the stratum corneum (SC) layer. To penetrate the SC barrier, we used a reverse micelle formulation that does not require high energy consumption processes for preparation. We aimed to enhance the skin permeability of HA by incorporating glyceryl monooleate&mdash, a skin permeation enhancer&mdash, into the formulation. A fluorescently-labeled HA-loaded reverse micelle formulation showed significantly enhanced permeation across Yucatan micro pig skin. Fourier transform infra-red spectroscopy of the surface of the skin treated with the reverse micelle formulation showed blue shifts of the CH2 symmetric/asymmetric stretching peaks, indicating a reduction in the barrier function of the SC. Further study revealed that HA was released from the reverse micelles at the hydrophobic/hydrophilic interface between the SC and the living epidermis. The results demonstrated that our reverse micellar system is an easy-to-prepare formulation for the effective transcutaneous delivery of HA.

Tazarotene and clobetasol propionate are efficacious for the treatment of psoriasis. The plasma pharmacokinetic assessments of tazarotene or clobetasol propionate have been reported. However, the pharmacokinetic characteristics of tazarotene and clobetasol propionate in skin when used together have not been studied. In the present study, sensitive and rapid methods were developed for the determination of clobetasol propionate, tazarotene and its active metabolite tazarotenic acid in Bama mini-pig skin by UPLC-MS/MS. After homogenization and pretreatment of skin samples, the separation was performed on a WondaSiL C18 column (4.6 × 150 mm, 5 μm) for tazarotene and clobetasol propionate. The separation of tazarotenic acid was achieved on a BDS HYPERSIL C18 column (4.6 × 100 mm, 2.4 μm). All the analytes were quantified with positive electrospray ionization and multiple reactions monitoring mode. The assay was validated in the range of 22-1111 ng/g for tazarotene and clobetasol propionate, 2-111 ng/g for tazarotenic acid in skin samples. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to evaluate the novel combination ointment of tazarotene and clobetasol propionate. The obtained intradermal content-time curves characterized the dermal absorption and metabolism features of the combination ointment. It was also found that there was no significant drug-drug interaction trend between tazarotene and clobetasol propionate. The obtained results would be essential for the development and clinical applications of this novel combination ointment.

In order to evaluate dermal absorption during typical working conditions in family farming, the amount of dimethoate on clothing and in the stratum corneum (SC) was measured in three rural workers. This was achieved by using cotton patches on the worker’s clothes and SC quantification by the tape stripping approach. To mimic the above study, an in vitro approach was performed using Franz cells by applying dimethoate (0.4 and 1.8 μg) direct to pig skin or, on a section of cotton before contact with pig skin. The in vivo case results demonstrated the high levels and variability of agrochemicals to which these farmers are subjected, with the total potential dermal absorption between 0.87–2.85 mg/person/h and the estimated SC penetration factor (PF) between 0–54.0 and 0–28.9 % for the back of the neck and the arms respectively. This probably demonstrates the impact of correct protective clothing. For the in vitro study, the amount of pesticide retained in the SC was 52.63 ± 10.73and 135.15 ± 31.8 ng/cm2 after applying 0.4 and 1.8 μg of pesticide directly on SC, and demonstrated close agreement with the in vivo approach. Further studies performed with this and other pesticides with different characteristics will contribute to the understanding of their transport through the skin.

A new way of delivering radiotherapy at very high dose rates is described and compared with conventional radiotherapy. The ultrahigh dose-rate therapy reduces damage to normal pig skin and exerts potent activity against spontaneous nasal tumors in cat patients. The implications for clinical development of this approach are discussed. See related article by Vozenin et al., p. 35

Although interstitial fluid (ISF) contains biomarkers of physiological significance and medical interest, sampling of ISF for clinical applications has made limited impact due to a lack of simple, clinically useful techniques that collect more than nanoliter volumes of ISF. This study describes experimental and theoretical analysis of ISF transport from skin using microneedle (MN) patches and demonstrates collection of1 µL of ISF within 20 min in pig cadaver skin and living human subjects using an optimized system. MN patches containing arrays of submillimeter solid, porous, or hollow needles were used to penetrate superficial skin layers and access ISF through micropores (µpores) formed upon insertion. Experimental studies in pig skin found that ISF collection depended on transport mechanism according to the rank order diffusioncapillary actionosmosispressure-driven convection, under the conditions studied. These findings were in agreement with independent theoretical modeling that considered transport within skin, across the interface between skin and µpores, and within µpores to the skin surface. This analysis indicated that the rate-limiting step for ISF sampling is transport through the dermis. Based on these studies and other considerations like safety and convenience for future clinical use, we designed an MN patch prototype to sample ISF using suction as the driving force. Using this approach, we collected ISF from human volunteers and identified the presence of biomarkers in the collected ISF. In this way, sampling ISF from skin using an MN patch could enable collection of ISF for use in research and medicine.

4-n-butyl resorcinol (4-nBR) is a highly effective tyrosinase inhibitor, and can be used in cosmetic product for depigmentation purpose. Its efficacy correlates with 4-nBR that absorbed by skin. In this study, skin distribution of 4-nBR within either human or pig skin ex vivo was studied and compared by three independent laboratories. Good agreement was observed in each compartment considering usual inter-lab variability. This study supports the use of pig skin as an alternative source of skin when the availability of human skin is a limiting factor.

The OECD test guideline 428 for the assessment of dermal absorption in vitro has been in force for more than a decade. Various sectors of industry utilise the method for the registration of chemical products. These include the Agrochemical and Cosmetic sectors where the OECD test guideline and industry-specific guidance forms a key part of the human risk assessment process for new and existing products. This investigation has compared the dermal absorption characteristics of one of the OECD 428 reference chemicals, testosterone, in human and pig dermatomed skin. We used identical dosing and skin decontamination conditions for testosterone in Franz static diffusion cells. This included a full mass balance recovery of the dose applied and distribution of the compound in the different layers of the skin. Our investigation has shown that intact human skin provides a more effective barrier to the dermal absorption of testosterone compared with pig skin, when studied according to modern day in vitro dermal absorption guidance.

The effects of the mixture of pig skin (PS) and coconut powder (CP) on the gelling and rheological properties of composite gel prepared with squid myofibrillar protein (MP) and lard were studied. The addition of PS and CP gel had significantly improved the water-holding capacity (WHC) and gelling properties of MP-Lard composite gel. Besides, composite gels with an adequate amount of PS and CP gel had a better texture and higher whiteness. The SDS-PAGE results showed that the presence of PS and CP gel did not affect the coagulated proteins in composite gels. The three-dimensional network structures of composite gels containing PS and CP gel were more compact and homogeneous. In general, the mixture of PS and CP could enhance the gel quality of MP-Lard composite gel and it could be used as a fat substitute in surimi products.

The aim of this project was to study the influence of microneedles on transdermal delivery of amantadine hydrochloride and pramipexole dihydrochloride across porcine ear skin in vitro. Microchannel visualization studies were carried out and characterization of the microchannel depth was performed using confocal laser scanning microscopy (CLSM) to demonstrate microchannel formation following microneedle roller application. We also report, for the first time, the use of TA.XT Plus Texture Analyzer to characterize burst force in pig skin for transdermal drug delivery experiments. This is the force required to rupture pig skin. The mean passive flux of amantadine hydrochloride, determined using a developed LC–MS/MS technique, was 22.38 ± 4.73 µg/cm2/h, while the mean flux following the use of a stainless steel microneedle roller was 49.04 ± 19.77 µg/cm2/h. The mean passive flux of pramipexole dihydrochloride was 134.83 ± 13.66 µg/cm2/h, while the flux following the use of a stainless steel microneedle roller was 134.04 ± 0.98 µg/cm2/h. For both drugs, the difference in flux values following the use of solid stainless steel microneedle roller was not statistically significantly (p &gt, 0.05). Statistical analysis was carried out using the Mann–Whitney Rank sum test.

Purpose To investigate the destruction of clinically-relevant bacteria within biofilms via the sustained release of the antibiotic tetracycline from zein-based electrospun polymeric fibrous matrices and to demonstrate the compatibility of such wound dressing matrices with human skin cells. Methods Zein/PCL triple layered fibrous dressings with entrapped tetracycline were electrospun. The successful entrapment of tetracycline in these dressings was validated. The successful release of bioactive tetracycline, the destruction of preformed biofilms, and the viability of fibroblast (FEK4) cells were investigated. Results The sustained release of tetracycline from these matrices led to the efficient destruction of preformed biofilms from Staphylococcus aureus MRSA252 in vitro, and of MRSA252 and ATCC 25923 bacteria in an ex vivo pig skin model using 1 × 1 cm square matrices containing tetracycline (30 μg). Human FEK4 cells grew normally in the presence of these matrices. Conclusions The ability of the zein-based matrices to destroy bacteria within increasingly complex in vitro biofilm models was clearly established. An ex vivo pig skin assay showed that these matrices, with entrapped tetracycline, efficiently kill bacteria and this, combined with their compatibility with a human skin cell line suggest these matrices are well suited for applications in wound healing and infection control.

A new approach to the formulation of resveratrol (RSV) entrapped niosomes for topical use is proposed in this work. Niosomes were formulated with Gelot 64 (G64) as surfactant, and two skin-compatible unsaturated fatty acids (oleic and linoleic acids), commonly used in pharmaceutical formulations, as penetration enhancers. Niosomes were prepared by two different methods: a thin film hydration method with minor modifications followed by a sonication stage (TFH-S), and an ethanol injection modified method (EIM). Niosomes prepared with the EIM method were in the range of 299-402 nm, while the TFH-S method produced larger niosomes in the range of 293-496 nm. Moreover, niosomes with higher RSV entrapment efficiency (EE) and better stability were generated by the EIM method. Ex vivo transdermal experiments, carried out in Franz diffusion cells on newborn pig skin, indicated that niosomes prepared by the EIM method were more effective for RSV penetration in epidermis and dermis (EDD), with values up to 21% for both penetration enhancers tested. The EIM method, which yielded the best RSV-entrapped niosomes, seems to be the most suitable for scaling up.