Bioconversion of retinol and its cell barrier function in human immortalized keratinocytes cells and artificial epidermis-dermis skin.

The current study aimed to characterize cellular uptake and bioconversion of retinol in fully differentiated human immortalized keratinocytes cells (HaCaT) and artificial skin by measuring the cell integrity of skin barriers, time-dependent transport of retinol, and bioconversion to its metabolites. The expression of epidermal differentiation related genes including Keratin 1 (KRT1), Keratin 10 (KRT10), and Involucrin (IVL) significantly increased in differentiated HaCaT. TEER of HaCaT did not decrease after incubating retinol compared to control (p > 0.05), indicating that retinol tends to maintain strength and integrity of epidermal barrier. TEER of artificial skin decreased treatment of retinol for 2 h, but it was recovered after 4 h. During retinol transport, metabolite was eluted at 13.37 and 13.82 min of basal medium of both keratinocytes and artificial skin, which was identified as retinoic acid by product ion of m/z 283.47. Retinol appeared to be accumulated in keratinocytes, but its uptake tends to be reduced in a time-dependent manner. Retinoic acid converted from retinol in keratinocytes was time dependently transported. In case of artificial skin, retinol was mostly found in apical at initial incubation time, but it was reduced during incubation for 24 h. Retinoic acid was time-dependently found in a basal, which was converted via epidermis-dermis. Results from the current study suggest that topical application of retinol to human skin optimal concentration and time exposure could maintain epidermal barrier function and promote skin function due to its remarkable bioconversion to retinoic acid in the epidermis-dermis.

A Tactile Skin System for Touch Sensing with Ultrasound Tomography.

The tomographic imaging method is promising in large-area touch-sensing applications. This paper presents a new type of such touch sensor using ultrasonic tomography (UST) via sound attenuation imaging. UST is gaining popularity as a portable, fast, and inexpensive imaging system for medical and industrial applications. UST can be developed in different operation modes. A transmission mode UST is being investigated as a force- and touch-sensitive skin. A prototype skin sensor was developed in a 200 mm diameter circular UST array containing two sets of 16 transducers, with one operating at a central frequency of 40 kHz and the other at 300 kHz. The extension of the sensor in terms of dimension, up to 400 mm diameter, and number of sensors, up to 32 transducers, is possible where eight points of contact were reconstructed successfully. The medium contains a 20 mm high water region, and a soft silicone membrane covers the liquid region. When touchpoints or forces are applied to the soft skin of the membrane, the sound pathway is disrupted, resulting in an image of the touch position and touch force intensity using a tomographic UST algorithm. Several static and dynamic experiments are conducted to demonstrate this novel application of UST. In addition, a correlation analysis is carried out to establish the force quantification potential for the UST-based tactile skin.

Multiparametric Quantitative Analysis of Photodamage to Skin Using Optical Coherence Tomography.

Ultraviolet (UV) irradiation causes 90% of photodamage to skin and long-term exposure to UV irradiation is the largest threat to skin health. To study the mechanism of UV-induced photodamage and the repair of sunburnt skin, the key problem to solve is how to non-destructively and continuously evaluate UV-induced photodamage to skin. In this study, a method to quantitatively analyze the structural and tissue optical parameters of artificial skin (AS) using optical coherence tomography (OCT) was proposed as a way to non-destructively and continuously evaluate the effect of photodamage. AS surface roughness was achieved based on the characteristic peaks of the intensity signal of the OCT images, and this was the basis for quantifying AS cuticle thickness using Dijkstra's algorithm. Local texture features within the AS were obtained through the gray-level co-occurrence matrix method. A modified depth-resolved algorithm was used to quantify the 3D scattering coefficient distribution within AS based on a single-scattering model. A multiparameter assessment of AS photodamage was carried out, and the results were compared with the MTT experiment results and H&E staining. The results of the UV photodamage experiments showed that the cuticle of the photodamaged model was thicker (56.5%) and had greater surface roughness (14.4%) compared with the normal cultured AS. The angular second moment was greater and the correlation was smaller, which was in agreement with the results of the H&E staining microscopy. The angular second moment and correlation showed a good linear relationship with the UV irradiation dose, illustrating the potential of OCT in measuring internal structural damage. The tissue scattering coefficient of AS correlated well with the MTT results, which can be used to quantify the damage to the bioactivity. The experimental results also demonstrate the anti-photodamage efficacy of the vitamin C factor. Quantitative analysis of structural and tissue optical parameters of AS by OCT enables the non-destructive and continuous detection of AS photodamage in multiple dimensions.

Evaluation of contraction of the split-thickness skin graft using three dermal matrices in the treatment of burn contractures: A randomised clinical trial.

Burn injuries commonly result in serious sequelae (such as skin contractures) in surviving patients, for which no single optimal solution is known. The goal of this study was to compare the late contraction of autologous skin grafts with or without dermal matrices used in the treatment of patients with burn contractures. This parallel design prospective, randomised and controlled clinical trial included patients with burn contracture treated using autologous skin grafts and dermal matrix. Patients were randomly assigned to one of the four groups: Integra® matrix (n = 10), Pelnac® matrix (n = 10), Matriderm® matrix (n = 9) or a Control Group (n = 10, without dermal matrix, only skin graft). The boundaries of skin defect were marked and transferred to a flat sterile surface for area measurement. The current area of the skin grafts was measured during surgery and compared with those obtained at 1, 3, 6 and 12 months postoperatively. Twelve months after surgery, the Control Group presented lower rates of skin graft contraction than Integra® (p < 0.01), Matriderm® (p = 0.01) and Pelnac® (p < 0.01) groups. Pelnac® resulted in larger skin graft contraction than Matriderm® (p < 0.01) and Integra® (p = 0.02), while differences between Integra® and Matriderm® were not significant (p = 0.16). The comparison between intraoperative and 12 months after surgery showed that the worst mean rates of skin graft contraction were from the Pelnac® (51.79%) and Matriderm® (59.17%). In patients with burn contractures, the use of these three dermal matrices did not reduce or avoid the occurrence of late contraction of the skin graft, so their use for this purpose should be carefully evaluated.

Effect of artificial skin membrane on the expression of miR-155 and miR-506-3p in patients with second-degree burns.

OBJECTIVE: To investigate the effect of artificial skin on the expression of miR-155 and miR-506-3p in patients with second-degree burns. METHODS: The study subjects included 50 patients with second-degree burns treated from July 2019 to July 2021. The control group received routine nursing, while the research group received both routine and artificial skin intervention simultaneously. The changes in wound tissue fibrosis and prognosis were observed. The expression levels of miR-155 and miR-506-3p and their downstream regulatory factors were detected and correlated with the rehabilitation of patients after artificial skin treatment. RESULTS: After treating second-degree burns with artificial skin membranes, the patient's wound tissue fibrosis and inflammation level improved. At the same time, the expression levels of miR-155 and miR-506-3p in related tests were higher than those in patients with available treatment. CONCLUSION: The effect of artificial skin membrane on the wound healing of second-degree burn patients may be realized by influencing the expression levels of miR-155 and miR-506-3p and their related signaling pathways.

Negative pressure wound therapy, artificial skin and autogenous skin implantation in diabetic foot ulcers.

OBJECTIVE: Diabetic foot ulcers (DFUs) are one of the most serious diabetic consequences, leading to amputations. Various therapies have been used to treat DFUs; however, a combination of negative pressure suction, artificial skin and autogenous skin implantation have never been investigated. This study aimed to evaluate the effectiveness of a novel three-step therapy protocol using negative pressure wound therapy (NPWT), artificial skin and autogenous skin implantation in patients with DFUs. METHOD: At a single tertiary university hospital between 2015 and 2018, the three-step therapy protocol was applied to patients with DFUs and its safety and efficacy was investigated. RESULTS: A total of 21 patients took part in the study. The majority of the patients were female (62%), with a mean age of 65 years and a mean body mass index of 21kg/m2. A third (n=7) of operative sites experienced minor complications, with two requiring re-operation. At a median follow up of 24 months, the average time of complete wound healing was 46 days, and the wound healing rate was 71%. The first-stage wound healing rate was 90%. All patients had achieved remission without any further recurrence of disease. CONCLUSION: This comprehensive surgical technique for managing DFUs achieved a high local cure rate, minimal functional morbidity, and acceptable wound complication rates. The three-step therapy protocol has the potential to promote the healing process of DFUs, which is expected to serve as a new method for the treatment and cure of DFUs.

Design, Fabrication and Characterisation of Multi-Parameter Optical Sensors Dedicated to E-Skin Applications.

For many years there has been a strong research interest in soft electronics for artificial skin applications. However, one challenge with stretchable devices is the limited availability of high performance, stretchable, electrical conductors and semiconductors that remain stable under strain. Examples of such electronic skin require excessive amounts of wires to address each sensing element-compression force and strain-in a conventional matrix structure. Here, we present a new process for fabricating artificial skin consisting of an optical waveguide architecture, enabling wide ranging sensitivity to external mechanical compression and strain. The manufacturing process allows design of a fully stretchable polydimethylsiloxane elastomer waveguide with embedded gratings, replicated from low cost DVD-Rs. This optical artificial skin allows the detection of compression forces from 0 to 3.8 N with controllable sensitivity. It also permits monitoring of elongation deformations up to 135%. This type of stretchable optical sensor is highly robust, transparent, and presents a large sensing area while limiting the amount of wires connecting to the sensor. Thus, this optical artificial skin presents far superior mechanical properties compared to current electronic skin.

Using Novel Multi-Frequency Analysis Methods to Retrieve Material and Temperature Information in Tactile Sensing Areas.

This article presents a novel artificial skin technology based on the Electric Impedance Tomography (EIT) that employs multi-frequency currents for detecting the material and the temperature of objects in contact with piezoresistive sheets. To date, few artificial skins in the literature are capable of detecting an object's material, e.g., wood, skin, leather, or plastic. EIT-based artificial skins have been employed mostly to detect the position of the contact but not its characteristics. Thanks to multi-frequency currents, our EIT-based artificial skin is capable of characterising the spectral profile of objects in contact and identifying an object's material at ambient temperature. Moreover, our model is capable of detecting several levels of temperature (from -10 up to 60 °C) and can also maintain a certain accuracy for material identification. In addition to the known capabilities of EIT-based artificial skins concerning detecting pressure and location of objects, as well as being low cost, these two novel modalities demonstrate the potential of EIT-based artificial skins to achieve global tactile sensing.

Temporary skin closure in extremity soft tissue sarcoma - our indications.

INTRODUCTION: Artificial skin replacements were developed to cover defects in general surgery or after burns. Their main indication in oncologic surgery is secondary resection of appropriate margins in skin tumors after incomplete primary excision. This is contraindicated in sarcomas where only wide excision is indicated. The aim of the study is to show rare possible indications for temporary skin closure (TSC) in extremity soft tissue sarcomas (STS). MATERIALS AND METHODS: Out of 594 patients with extremity STS treated surgically at the Department of Orthopedics, University Hospital Bulovka, Prague, since 2014, we evaluated those with TSC concerning their indications. RESULTS: TSC (Aquagel twice, Parasorb four times, and COM 30 five times) was used in 11 patients. Six cases were on the foot, three on the femur and two on the lower legs. Seven cases were high-grade sarcomas, two cases were synovial sarcomas, one case was low-grade myxofibrosarcoma and one case was low-grade malignant peripheral nerve sheath tumor. We covered tendons five times, bones four times and vessels once. Ten of the 11 cases were recurrent tumors with extensive reconstructions, an increased risk of infection or unclear final histology. Two-stage surgeries seem good indications to decrease the adverse effects of prolonged surgery on flap perfusion or patients status. DISCUSSION: Not only the anesthesiologic, but also oncologic factors, potentiating the adverse effects of prolonged surgery on the patient and flaps, are discussed. The pros and cons of individual indications and their alternatives are compared. CONCLUSION: The indications for TSC in extremity STS are rare, but exist. TSC can be a good solution, enabling a safe two-stage reconstruction at a specialized plastic surgery unit, after an initial wide excision at a department of oncologic surgery. This can be a safer method concerning the perfusion of flaps and general status of an oncologic patient.

Percutaneous fetoscopic spina bifida repair: effect on ambulation and need for postnatal cerebrospinal fluid diversion and bladder catheterization.

OBJECTIVE: A trial comparing prenatal with postnatal open spina bifida (OSB) repair established that prenatal surgery was associated with better postnatal outcome. However, in the trial, fetal surgery was carried out through hysterotomy. Minimally invasive approaches are being developed to mitigate the risks of open maternal-fetal surgery. The objective of this study was to investigate the impact of a novel neurosurgical technique for percutaneous fetoscopic repair of fetal OSB, the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique, on long-term postnatal outcome. METHODS: This study examined descriptive data for all patients undergoing fetoscopic OSB repair who had available 12- and 30-month follow-up data for assessment of need for cerebrospinal fluid (CSF) diversion and need for bladder catheterization and ambulation, respectively, from eight centers that perform prenatal OSB repair via percutaneous fetoscopy using a biocellulose patch between the neural placode and skin/myofascial flap, without suture of the dura mater (SAFER technique). Univariate and multivariate logistic regression analyses were used to examine the effect of different factors on need for CSF diversion at 12 months and ambulation and need for bladder catheterization at 30 months. Potential cofactors included gestational age at fetal surgery and delivery, preoperative ultrasound findings of anatomical level of the lesion, cerebral lateral ventricular diameter, lesion type and presence of bilateral talipes, as well as postnatal findings of CSF leakage at birth, motor level, presence of bilateral talipes and reversal of hindbrain herniation. RESULTS: A total of 170 consecutive patients with fetal OSB were treated prenatally using the SAFER technique. Among these, 103 babies had follow-up at 12 months of age and 59 had follow-up at 30 months of age. At 12 months of age, 53.4% (55/103) of babies did not require ventriculoperitoneal shunt or third ventriculostomy. At 30 months of age, 54.2% (32/59) of children were ambulating independently and 61.0% (36/59) did not require chronic intermittent catheterization of the bladder. Multivariate logistic regression analysis demonstrated that significant prediction of need for CSF diversion was provided by lateral ventricular size and type of lesion (myeloschisis). Significant predictors of ambulatory status were prenatal bilateral talipes and anatomical and functional motor levels of the lesion. There were no significant predictors of need for bladder catheterization. CONCLUSION: Children who underwent prenatal OSB repair via the percutaneous fetoscopic SAFER technique achieved long-term neurological outcomes similar to those reported in the literature after hysterotomy-assisted OSB repair. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The effect of combined curcumin-mediated photodynamic therapy and artificial skin on Staphylococcus aureus-infected wounds in rats.

Healing wounds represent a major public health problem, mainly when it is infected. Besides that, the antibiotics misuse and overuse favor the development of bacterial resistance. This study evaluated the effects of antimicrobial photodynamic therapy (aPDT) combined with artificial skin on disinfection of infected skin wound in rats. Twenty-four Wistar rats were randomly distributed into 4 groups (n = 6): (i) control-untreated; (ii) aPDT-treated with curcumin-mediated aPDT (blue light); (iii) artificial skin-treated with artificial skin alcohol-based; and (iv) aPDT plus artificial skin-treated with aPDT associated with artificial skin alcohol-based. For the in vivo model, a full-thickness biopsy with 0.80 cm was performed in order to inoculate the microorganism Staphylococcus aureus (ATCC 25923). The aPDT was performed with a curcumin gel and a blue LED light (450 nm, 80 mW/cm2) at the dose of 60 J/cm2 and the treatment with alcohol-based artificial skin was done with the topical application of 250 µL. Additional animals were submitted to aPDT combined with the artificial skin. After treatments, the number of colony-forming units (CFU) and the damage area were determined. Data were analyzed by two-way repeated measures ANOVA and Tukey tests. The highest reduction of the bacterial viability was observed in the PDT plus artificial skin group (4.14 log10), followed by artificial skin (2.38 log10) and PDT (2.22 log10) groups. In addition, all treated groups showed higher relative area of wound contraction (36.21% for the PDT, 38.41% for artificial skin, and 35.02% for PDT plus artificial) in comparison with the control group. These findings provide evidence for the positive benefits of aPDT with blue light and curcumin associated with artificial skin to decontaminate and accelerate the wound contraction.

A Frequency Modulation-Based Taxel Array: A Bio-Inspired Architecture for Large-Scale Artificial Skin.

This work introduces an array prototype based on a Frequency Modulation (FM) encoding architecture to transfer multiple sensor signals on a single wire. The use case presented adopts Hall-effect sensors as an example to represent a much larger range of sensor types (e.g., proximity and temperature). This work aims to contribute to large area artificial skin systems which are a key element to enhance robotic platforms. Artificial skin will allow robotic platforms to have spatial awareness which will make interaction with objects and users safe. The FM-based architecture has been developed to address limitations in large-scale artificial skin scalability. Scalability issues include power requirements; number of wires needed; as well as frequency, density, and sensitivity bottlenecks. In this work, eight sensor signals are simultaneously acquired, transferred on a single wire and decoded in real-time. The overall taxel array current consumption is 36 mA. The work experimentally validates and demonstrates that different input signals can be effectively transferred using this approach minimizing wiring and power consumption of the taxel array. Four different tests using single as well as multiple stimuli are presented. Observations on performances, noise, and taxel array behaviour are reported. The results show that the taxel array is reliable and effective in detecting the applied stimuli.

Carbon/Silicone Nanocomposite-Enabled Soft Pressure Sensors with a Liquid-Filled Cell Structure Design for Low Pressure Measurement.

In the fields of humanoid robots, soft robotics, and wearable electronics, the development of artificial skins entails pressure sensors that are low in modulus, high in sensitivity, and minimal in hysteresis. However, few sensors in the literature can meet all the three requirements, especially in the low pressure range (<10 kPa). This article presents a design for such pressure sensors. The bioinspired liquid-filled cell-type structural design endows the sensor with appropriate softness (Young's modulus < 230 kPa) and high sensitivity (highest at 0.7 kPa-1) to compression forces below 0.65 N (6.8 kPa). The low-end detection limit is ~0.0012 N (13 Pa), only triple the mass of a bee. Minimal resistance hysteresis of the pressure sensor is 7.7%. The low hysteresis is attributed to the study on the carbon/silicone nanocomposite, which reveals the effect of heat treatment on its mechanical and electromechanical hysteresis. Pressure measurement range and sensitivity of the sensor can be tuned by changing the structure and strain gauge parameters. This concept of sensor design, when combined with microfluidics technology, is expected to enable soft, stretchable, and highly precise touch-sensitive artificial skins.

A Phase Inversion-Based Microfluidic Fabrication of Helical Microfibers towards Versatile Artificial Abdominal Skin.

Microfluidic spinning technology (MST), incorporating microfluidics with chemical reactions, has gained considerable interest for constructing anisotropic advanced microfibers, especially helical microfibers. However, these efforts suffer from the limited material choices, restricting their applications. Here, a new phase inversion-based microfluidic spinning (PIMS) method is proposed for producing helical microfibers. This method undergoes a physicochemical phase inversion process, which is capable of efficiently manufacturing strong (tensile stress of more than 25 MPa), stretchable, flexible and biocompatible helical microfibers. The helical microfibers can be used to fabricate bi-oriented stretchable artificial abdominal skin, preventing incisional hernia formation and promoting the wound healing without conglutination. This research not only offers a universal approach to design helical microfibers but also provides a new insight into artificial skin.

Microfluidic Skin-on-a-Chip Models: Toward Biomimetic Artificial Skin.

The role of skin in the human body is indispensable, serving as a barrier, moderating homeostatic balance, and representing a pronounced endpoint for cosmetics and pharmaceuticals. Despite the extensive achievements of in vitro skin models, they do not recapitulate the complexity of human skin; thus, there remains a dependence on animal models during preclinical drug trials, resulting in expensive drug development with high failure rates. By imparting a fine control over the microenvironment and inducing relevant mechanical cues, skin-on-a-chip (SoC) models have circumvented the limitations of conventional cell studies. Enhanced barrier properties, vascularization, and improved phenotypic differentiation have been achieved by SoC models; however, the successful inclusion of appendages such as hair follicles and sweat glands and pigmentation relevance have yet to be realized. The present Review collates the progress of SoC platforms with a focus on their fabrication and the incorporation of mechanical cues, sensors, and blood vessels.

Mesenchymal stromal cells from dermal and adipose tissues induce macrophage polarization to a pro-repair phenotype and improve skin wound healing.

The process of wound healing restores skin homeostasis but not full functionality; thus, novel therapeutic strategies are needed to accelerate wound closure and improve the quality of healing. In this context, tissue engineering and cellular therapies are promising approaches. Although sharing essential characteristics, mesenchymal stromal cells (MSCs) isolated from different tissues might have distinct properties. Therefore, the aim of this study was to comparatively investigate, by a mouse model in vivo assay, the potential use of dermal-derived MSCs (DSCs) and adipose tissue-derived MSCs (ASCs) in improving skin wound healing. Human DSCs and ASCs were delivered to full-thickness mouse wounds by a collagen-based scaffold (Integra Matrix). We found that the association of both DSCs and ASCs with the Integra accelerated wound closure in mice compared with the biomaterial only (control). Both types of MSCs stimulated angiogenesis and extracellular matrix remodeling, leading to better quality scars. However, the DSCs showed smaller scar size,superior extracellular matrix deposition, and greater number of cutaneous appendages. Besides, DSCs and ASCs reduced inflammation by induction of macrophage polarization from a pro-inflammatory (M1) to a pro-repair (M2) phenotype. In conclusion, both DSCs and ASCs were able to accelerate the healing of mice skin wounds and promote repair with scars of better quality and more similar to healthy skin than the empty scaffold. DSCs associated with Integra induced superior overall results than the Integra alone, whereas scaffolds with ASCs showed an intermediate effect, often not significantly better than the empty biomaterial.

Complex approach to skin repair in an extensively burned child: a case study.

The limited amount of donor sites and loss of dermis are major challenges in the therapy of extensively burned patients. Here, we present a complex treatment approach of an eight-year-old boy with full-thickness burns on 90% of the total body surface area, using simple and efficient techniques of tissue engineering. To obtain sufficient skin for grafting we repeatedly harvested the same anatomical areas. Acceleration of donor site healing was achieved by treatment with a suspension of noncultured autologous skin cells (NASC) and acellular porcine dermis (Xe-Derma (XD), Czech Republic). Moreover, such wound management allowed up to six reharvestings, compared with one-to-three procedures following routine treatment. Bilayer Integra template (Integra LifeSciences Corp., US) was used as the dermal substitute in over 60% of full-thickness burns. Following successful vascularisation of the neodermis in 3-4 weeks, the templates were covered with meshed split-thickness skin grafts (STSG), or Meek autografts, and facilitated by NASC/XD. We may conclude that such a 'sandwich' technique approach, combining four biological covers (Integra, STSG, NASC and XD), significantly contributed to the successful skin repair of the patient.

PVDF-TrFE-Based Stretchable Contact and Non-Contact Temperature Sensor for E-Skin Application.

Development of stretchable electronics has been driven by key applications such as electronics skin for robotic or prosthetic. Mimicking skin functionalities imposes at a minimal level: stretchability, pressure, and temperature sensing capabilities. While the research on pressure sensors for artificial skin is extensive, stretchable temperature sensors remain less explored. In this work, a stretchable temperature and infrared sensor has been developed on a polydimethylsiloxane substrate. The sensor is based on poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) as a pyroelectric material. This material is sandwiched between two electrodes. The first one consists of aluminium serpentines, covered by gold in order to get electrical contact and maximum stretchability. The second one is based on poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) that has shown good electrical compatibility with PVDF-TrFE and provides the stretchability of the top electrode. Without poling the PVDF-TrFE, sensor has shown a sensitivity of around 7 pF.°C-1 up to 35% strain without any change in its behaviour. Then, taking advantage on infrared absorption of PEDOT:PSS, a poled device has shown a pyroelectric peak of 13 mV to an infrared illumination of 5 mW at 830 nm. This stretchable device valuably allows an electronic skin (e-skin) use for contact and more importantly non-contact thermal sensing.

STAT3 signalling pathway is implicated in keloid pathogenesis by preliminary transcriptome and open chromatin analyses.

Keloids are wounding-induced fibroproliferative human tumor-like skin scars of complex genetic makeup and poorly defined pathogenesis. To reveal dynamic epigenetic and transcriptome changes of keloid fibroblasts, we performed RNA-seq and ATAC-seq analysis on an early passage keloid fibroblast cell strain and its paired normal control fibroblasts. This keloid strain produced keloid-like scars in a plasma clot-based skin equivalent humanized keloid animal model. RNA-seq analysis reveals gene ontology terms including hepatic fibrosis, Wnt-ß-catenin, TGF-ß, regulation of epithelial-mesenchymal transition (EMT), STAT3 and adherens junction. ATAC-seq analysis suggests STAT3 signalling is the most significantly enriched gene ontology term in keloid fibroblasts, followed by Wnt signalling (Wnt5) and regulation of the EMT pathway. Immunohistochemistry confirms that STAT3 (Tyr705 phospho-STAT3) is activated and ß-catenin is up-regulated in the dermis of keloid clinical specimens and keloid skin equivalent implants from the humanized mouse model. A non-linear dose-response of cucurbitacin I, a selective JAK2/STAT3 inhibitor, in collagen type I expression of keloid-derived plasma clot-based skin equivalents implicates a likely role of STAT3 signalling in keloid pathogenesis. This work also demonstrates the utility of the recently established humanized keloid mouse model in exploring the mechanism of keloid formation.

Determining the factors affecting dynamic insertion of microneedles into skin.

Microneedles are extremely small and minimally-invasive intradermal drug delivery devices that require controlled, accurate, and repeatable insertions into human skin to perform their functions. Due to high variability and elasticity of human skin, dynamic insertion methods are being sought to ensure success in microneedle insertions into the skin passed the tough stratum corneum layer. Dynamic microneedle insertions have not been thoroughly studied to identify and assess the key parameters influencing the skin fracture to date. Here, we have utilized a previously validated artificial mechanical human skin model to identify and evaluate the factors affecting microneedle insertion. It was determined that a microneedle's velocity at impact against the skin played the most crucial role in successfully inserting microneedle devices of different geometrical features (i.e., tip area) and array size (i.e., number of projections). The findings presented herein will facilitate the development of automated microneedle insertion devices that will enable user-friendly and error-free applications of microneedle technologies for medicine delivery.