Topical Nanoliposomal Collagen Delivery for Targeted Fibril Formation by Electrical Stimulation.

Collagen is a complex, large protein molecule that presents a challenge in delivering it to the skin due to its size and intricate structure. However, conventional collagen delivery methods are either invasive or may affect the protein's structural integrity. This study introduces a novel approach involving the encapsulation of collagen monomers within zwitterionic nanoliposomes, termed Lip-Cols, and the controlled formation of collagen fibrils through electric fields (EF) stimulation. The results reveal the self-assembly process of Lip-Cols through electroporation and a pH gradient change uniquely triggered by EF, leading to the alignment and aggregation of Lip-Cols on the electrode interface. Notably, Lip-Cols exhibit the capability to direct the orientation of collagen fibrils within human dermal fibroblasts. In conjunction with EF, Lip-Cols can deliver collagen into the dermal layer and increase the collagen amount in the skin. The findings provide novel insights into the directed formation of collagen fibrils via electrical stimulation and the potential of Lip-Cols as a non-invasive drug delivery system for anti-aging applications.

Novel human skin surface antimicrobial peptide quantification method using a skin patch test chamber: A pilot study.

INTRODUCTION: Antimicrobial peptides (AMPs) on the skin surface are related to the innate immunity of the skin in preventing external infection. Skin rinsing and tape stripping (TS) are acceptable methods for analyzing AMPs on the skin surface but have limitations, such as causing skin damage. In this study, we proposed a noninvasive method to measure AMPs on the skin surface with minimal skin damage. METHODS: Using the patch test assay, we aimed to analyze the skin surface human ß-defensin (hBDs) levels without damaging the skin barrier. The concentrations of hBDs on the skin surface were evaluated through the skin patch testing of 13 healthy subjects, and hBD-1 concentrations were compared with those obtained using the TS method in this proof-of-concept study. In addition, changes in skin physiology and concentration of hBDs under 1% sodium lauryl sulfate stimulation were monitored in 14 healthy subjects (8 young and 6 elderly subjects) for 150 h. RESULTS: The correlation between the two methods had a Pearson's coefficient of 0.640, and skin patch analysis led to a relatively less impaired barrier with no significant increase in transepidermal water loss after analysis. Age-specific comparisons suggested that higher skin surface hBD-2 concentrations were present in the young group as compared with the elderly group. Skin surface expression of hBD-2 after skin barrier disruption was also higher in the young group. CONCLUSION: Our findings show that skin patch analysis is a convenient method to analyze hBDs on the skin surface. hBDs are factors of innate immunity that can be used as an index to predict a decreased chemical immune response of skin due to aging.

Effects of arginine glutamate (RE:pair) on wound healing and skin elasticity improvement after CO2 laser irradiation.

BACKGROUND: Glutamic acid is known to be effective for keratinocyte proliferation, but its dermatological application is limited due to its poor solubility in water and various solvents. AIM: Here, the efficacy of the arginine glutamate ion pair (named as RE:pair) for recovering damaged skin and improving skin elasticity was investigated through the analysis of keratinocyte proliferation and collagen synthesis. METHODS: Following the structural analysis of RE:pair using spectroscopic methods, a scratch assay, and Pro-Collagen I ELISA, skin tissue changes in wound-induced artificial skin, changes in wound area after laser wound induction, and the sensory evaluation of skin improvement were investigated. RESULTS: As a result of scratch assay, wound recovery of 94.55% ± 9.57% was confirmed at 10 ppm RE:pair treatment. When evaluation of expression efficacy of procollagen type I, it was found that the expression rate was increased by 32.47% ± 5.62% compared with the control group. Further, the upregulation of the proliferation marker Ki-67 and filaggrin expression in the damage-induced artificial skin was verified. Clinically, the improvement was subjectively verified in terms of the reduction of the wound area, the restoration of the barrier, the improvement of skin elasticity, and through the sensory experience of skin improvement. CONCLUSION: RE:pair shows a greater therapeutic effect than the individual effects of its constituent amino acids and those of the simple mixtures of these compounds. RE:pair exerts its therapeutic action by promoting the proliferation of keratinocytes and enhancing collagen synthesis in fibroblasts. Accordingly, it can be used throughout the cosmetic industry as an effective amino acid wound healing and skin elasticity improving material.

A Simple Route of Printing Explosive Crystalized Micro-Patterns by Using Direct Ink Writing.

The production of energetic crystalized micro-patterns by using one-step printing has become a recent trend in energetic materials engineering. We report a direct ink writing (DIW) approach in which micro-scale energetic composites composed of 1,3,5-trinitro-1,3,5-triazinane (RDX) crystals in selected ink formulations of a cellulose acetate butyrate (CAB) matrix are produced based on a direct phase transformation from organic, solvent-based, all-liquid ink. Using the formulated RDX ink and the DIW method, we printed crystalized RDX micro-patterns of various sizes and shapes on silicon wafers. The crystalized RDX micro-patterns contained single crystals on pristine Si wafers while the micro-patterns containing dendrite crystals were produced on UV-ozone (UVO)-treated Si wafers. The printing method and the formulated all-liquid ink make up a simple route for designing and printing energetic micro-patterns for micro-electromechanical systems.

An Accelerated Wound-Healing Surgical Suture Engineered with an Extracellular Matrix.

A suture is a ubiquitous medical device to hold wounded tissues together and support the healing process after surgery. Surgical sutures, having incomplete biocompatibility, often cause unwanted infections or serious secondary trauma to soft or fragile tissue. In this research, UV/ozone (UVO) irradiation or polystyrene sulfonate acid (PSS) dip-coating is used to achieve a fibronectin (FN)-coated absorbable suture system, in which the negatively charged moieties produced on the suture cause fibronectin to change from a soluble plasma form into a fibrous form, mimicking the actions of cellular fibronectin upon binding. The fibrous fibronectin coated on the suture can be exploited as an engineered interface to improve cellular migration and adhesion in the region around the wounded tissue while preventing the binding of infectious bacteria, thereby facilitating wound healing. Furthermore, the FN-coated suture is found to be associated with a lower friction between the suture and the wounded tissue, thus minimizing the occurrence of secondary wounds during surgery. It is believed that this surface modification can be universally applied to most kinds of sutures currently in use, implying that it may be a novel way to develop a highly effective and safer suture system for clinical applications.

Influence of quarantine mask use on skin characteristics: One of the changes in our life caused by the COVID-19 pandemic.

BACKGROUND: The influence of various environmental factors on skin properties is well known. However, there is a lack of research into the effect of quarantine masks on skin properties, even though the use of masks has significantly increased after the COVID-19 outbreak. Therefore, this study aimed to investigate the influence of mask use on skin properties. MATERIALS AND METHODS: Twenty subjects were enrolled in this study. The subjects used approved quarantine masks for 6 hours a day for 2 weeks. We measured eight skin biophysical parameters: temperature, redness, pore volume, texture, elasticity, trans-epidermal water loss (TEWL), sebum content, and pH, and evaluated acne lesions before and after using quarantine masks. The evaluation was performed on the mask-wearing area of the face. RESULTS: Skin temperature, redness, and TEWL increased significantly after a 6-hour mask use, while the sebum content increased marginally. Skin elasticity was reduced by the use of masks over 1 and 2 weeks, whereas the pore volume and the number of acne lesions increased after a 2-week mask use. The skin changes caused by mask use showed sex-based differences in the skin elasticity (after 6 hours), redness, and roughness (after 2 weeks). CONCLUSIONS: The use of quarantine masks causes a change in the skin temperature, redness, and TEWL in the short term and in skin elasticity, pores, and acne in the long term. This study revealed that prolonged mask use could have negative effects on the skin.

Topical application of Zanthoxylum piperitum extract improves lateral canthal rhytides by inhibiting muscle contractions.

Facial wrinkles are the predominant phenotypes of skin aging. To date, one of the most effective ways to improve wrinkles is botulinum toxin type A (BoNT/A) injection, which inhibits muscle contractions by reducing acetylcholine release from neurons. However, since BoNT/A is a hazardous neurotoxin, the injection can only be performed by medical doctors and the procedure is only possible through invasive injection, causing inconveniences such as pain. To overcome these inconveniences, we tried to find a way to reduce wrinkles non-invasively via mechanisms similar to BoNT/A. We first designed in vitro assays to test BoNT/A-like muscle contraction inhibition in two different model systems. By using the assays, we identified Zanthoxylum piperitum (Z. piperitum) fruit extract as a BoNT-like reagent (27.7% decrease of muscle contraction rates by 1000 ppm of Z. piperitum extract treatment). Next, we determined mechanisms of how Z. piperitum extract decreases muscle contraction rates and found that the extract treatment inhibits electrical signal transduction in neurons. We also showed that among known components of Z. piperitum extract, quercitrin is responsible for muscle contraction inhibition. We further identified that Z. piperitum extract has synergistic effects with acetyl hexapeptide-8 and BoNT/A light chain, which are well-known BoNT-like peptides. Finally, we showed that topical treatment of the Z. piperitum extract indeed decreases facial wrinkles and treatment of Z. piperitum extract with acetyl hexapeptide-8 has a tendency to improve wrinkles synergistically (14.5% improvement on average). The synergistic effect of the combination is expected to improve wrinkles effectively by implementing the BoNT/A mechanisms in a non-invasive way.

Performance of Glass Wool Fibers in Asphalt Concrete Mixtures.

Nowadays, in order to improve asphalt pavement performance and durability and reduce environmental pollution caused by hydrocarbon materials, many researchers are studying different ways of modifying asphalt concrete (AC) and finding alternative paving materials to extend the service life of pavements. One of the successful materials used in the modification of AC is fibers. Different types of fibers have been reinforced in AC mixtures and improvements have been observed. This research studies the performance of glass wool fibers reinforced in a dense-graded asphalt mixture. Generally, glass fibers are known to have excellent mechanical properties such as high tensile modulus, 100% elastic recovery and a very high tolerance to heat. Glass wool fibers are commonly used as a thermal insulation material. In this research, to evaluate the performance of glass wool fibers in AC, laboratory tests, the Marshall mix design test, indirect tensile strength (IDT), tensile strength ratio (TSR) and the Kim test were conducted to determine a proper mix design, tensile properties, moisture susceptibility, rutting and fatigue behaviors. Results show that the addition of glass wool fibers does affect the properties of AC mixtures. The use of glass wool fibers shows a positive consistence result, in which it improved the moisture susceptibility and rutting resistance of the AC. Additionally, results show that the addition of fiber increased tensile strength and toughness which indicates that fibers have a potential to resist distresses that occur on a surface of the road as a result of heavy traffic loading. The overall results show that the addition of glass wool fibers in AC mixtures is beneficial in improving properties of AC pavements.

Recent Advances in Microfluidic Paper-Based Analytical Devices toward High-Throughput Screening.

Microfluidic paper-based analytical devices (µPADs) have become promising tools offering various analytical applications for chemical and biological assays at the point-of-care (POC). Compared to traditional microfluidic devices, µPADs offer notable advantages; they are cost-effective, easily fabricated, disposable, and portable. Because of our better understanding and advanced engineering of µPADs, multistep assays, high detection sensitivity, and rapid result readout have become possible, and recently developed µPADs have gained extensive interest in parallel analyses to detect biomarkers of interest. In this review, we focus on recent developments in order to achieve µPADs with high-throughput capability. We discuss existing fabrication techniques and designs, and we introduce and discuss current detection methods and their applications to multiplexed detection assays in relation to clinical diagnosis, drug analysis and screening, environmental monitoring, and food and beverage quality control. A summary with future perspectives for µPADs is also presented.

Quantitatively controllable fluid flows with ballpoint-pen-printed patterns for programmable photo-paper-based microfluidic devices.

Regulating the fluid flow in microfluidic devices enables a wide range of assay protocols for analytical applications. A programmable, photo-paper-based microfluidic device fabricated by using a method of cutting and laminating, followed by printing, is reported. The flow distance of fluid in the photo-paper-based channel was linearly proportional to time. By printing silver nanoparticle (AgNP) and poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole-co-tetrafluoroethylene] (PTFE) patterns on the surface of a photo-paper-based channel, we were able to either increase or decrease the fluid flow in the fabricated microfluidic devices, while maintaining the linearity in the flow distance-time relation. In comparison to the speed of fluid flow in a pristine channel, by using hydrophilic AgNP patterns, we were able to increase the speed in the channel by up to 15 times while we were able to slow the speed by a factor of 3 when using hydrophobic PTFE dots. We then further demonstrated a single-step protocol for detecting glucose and a multi-step protocol for detecting methyl paraoxon (MPO) with our methods in photo-paper-based microfluidic devices. This approach can lead to improved fluid handling techniques to achieve a wide range of complex, but programmable, assays without the need for any additional auxiliary devices for automated operation.

3D paper-based microfluidic device: a novel dual-detection platform of bisphenol A.

A novel platform of microfluidic paper-based analytical devices (µPADs) for dual detection of bisphenol A (BPA), a model analyte, was fabricated using an electronic digital plotter to create the stacked layer of µPADs and generate the lateral-flow channel without using an external pump. Two detection techniques, including electrochemical detection and laser desorption ionization mass spectrometric detection (LDI-MS), were used complementarily to improve the precision in the detection of BPA. The fluid sample was delivered to both detection zones by the capillary action, automatically generated from the fabricated microfluidic device. For an electrochemical sensor, two ballpoint pens filled with silver nanoparticles (AgNPs) and multiwall carbon nanotube (MWCNT) ink were used to print onto the paper with a contact printing method using a digital plotter. To further improve the sensitivity, zinc oxide (ZnO) was used to modify both electrochemical and LDI-MS detection zones. For BPA detection, high electrocatalytic properties and strong UV absorption of ZnO promote the electron transfer in the electrochemical sensor and ionization efficiency in LDI-MS with low interferences compared with a conventional organic matrix. Under optimal conditions, this platform showed a dual detection capability for BPA with a detection limit of 0.35 µM for electrochemical detection and with an ultralow detection limit of 0.01 pM for LDI-MS. This novel platform might be very useful for trace analyses requiring high precision detection of various analytes.

Inkjet-Printed Carbon Nanotubes for Fabricating a Spoof Fingerprint on Paper.

A spoof fingerprint was fabricated on paper and applied for a spoofing attack to unlock a smartphone on which a capacitive array of sensors had been embedded with a fingerprint recognition algorithm. Using an inkjet printer with an ink made of carbon nanotubes (CNTs), we printed a spoof fingerprint having an electrical and geometric pattern of ridges and furrows comparable to that of the real fingerprint. With this printed spoof fingerprint, we were able to unlock a smartphone successfully; this was due to the good quality of the printed CNT material, which provided electrical conductivities and structural patterns similar to those of the real fingerprint. This result confirms that inkjet-printing CNTs to fabricate a spoof fingerprint on paper is an easy, simple spoofing route from the real fingerprint and suggests a new method for outputting the physical ridges and furrows on a two-dimensional plane.

Programmable Paper-Based Microfluidic Devices for Biomarker Detections.

Recent advanced paper-based microfluidic devices provide an alternative technology for the detection of biomarkers by using affordable and portable devices for point-of-care testing (POCT). Programmable paper-based microfluidic devices enable a wide range of biomarker detection with high sensitivity and automation for single- and multi-step assays because they provide better control for manipulating fluid samples. In this review, we examine the advances in programmable microfluidics, i.e., paper-based continuous-flow microfluidic (p-CMF) devices and paper-based digital microfluidic (p-DMF) devices, for biomarker detection. First, we discuss the methods used to fabricate these two types of paper-based microfluidic devices and the strategies for programming fluid delivery and for droplet manipulation. Next, we discuss the use of these programmable paper-based devices for the single- and multi-step detection of biomarkers. Finally, we present the current limitations of paper-based microfluidics for biomarker detection and the outlook for their development.

Affordable Fabrication of Conductive Electrodes and Dielectric Films for a Paper-based Digital Microfluidic Chip.

In order to fabricate a digital microfluidic (DMF) chip, which requires a patterned array of electrodes coated with a dielectric film, we explored two simple methods: Ballpoint pen printing to generate the electrodes, and wrapping of a dielectric plastic film to coat the electrodes. For precise and programmable printing of the patterned electrodes, we used a digital plotter with a ballpoint pen filled with a silver nanoparticle (AgNP) ink. Instead of using conventional material deposition methods, such as chemical vapor deposition, printing, and spin coating, for fabricating the thin dielectric layer, we used a simple method in which we prepared a thin dielectric layer using pre-made linear, low-density polyethylene (LLDPE) plastic (17-µm thick) by simple wrapping. We then sealed it tightly with thin silicone oil layers so that it could be used as a DMF chip. Such a treated dielectric layer showed good electrowetting performance for a sessile drop without contact angle hysteresis under an applied voltage of less than 170 V. By using this straightforward fabrication method, we quickly and affordably fabricated a paper-based DMF chip and demonstrated the digital electrofluidic actuation and manipulation of drops.

Effects of Silicone Oil on Electrowetting to Actuate a Digital Microfluidic Drop on Paper.

The effects of an immiscible, lubricating polydimethylsiloxane fluid, referred to as silicone oil, on the static deformation and on the dynamic motion of a water drop on paper induced by electrowetting were investigated. The deformation of a drop on a hydrophobic film of amorphous fluoropolymers top-coated with less hydrophobic silicone oil was much more predictable, reversible and reproducible than on the uncoated surface. In the dynamic tribological experiment for a sliding drop along an inclined surface, a significant decrease in the friction coefficient, with an unexpected dependency of the contact area, was observed. Based on the curve fitting analysis, the shear stress and the net friction force were estimated quantitatively. Because of the tribological effect and the reduced shear friction force of the oil film, the static and the dynamic electrowetting states of the water drop were enhanced.

Paper-Based Bimodal Sensor for Electronic Skin Applications.

We present the development of a flexible bimodal sensor using a paper platform and inkjet printing method, which are suited for low-cost fabrication processes and realization of flexible devices. In this study, we employed a vertically stacked bimodal device architecture in which a temperature sensor is stacked on top of a pressure sensor and operated on different principles, allowing the minimization of interference effects. For the temperature sensor placed in the top layer, we used the thermoelectric effect and formed a closed-loop thermocouple composed of two different printable inks (conductive PEDOT:PSS and silver nanoparticles on a flexible paper platform) and obtained temperature-sensing capability over a wide range (150 °C). For the pressure sensor positioned in the bottom layer, we used microdimensional pyramid-structured poly(dimethylsiloxane) coated with multiwall carbon nanotube conducting ink. Our pressure sensor exhibits a high-pressure sensitivity over a wide range (100 Pa to 5 kPa) and high-endurance characteristics of 105. Our 5 × 5 bimodal sensor array demonstrates negligible interference, high-speed responsivity, and robust sensing characteristics. We believe that the material, process, two-terminal device, and integration scheme developed in this study have a great value that can be widely applied to electronic skin.

Size-Dependent Cellular Uptake of Trans-Activator of Transcription Functionalized Nanoparticles.

We investigated the cellular uptake efficiencies of differently-sized silica nanoparticles in the presence and the absence of trans-activator of transcription (TAT) peptide. Silica nanoparticles incorporating fluorescent dye molecules with diameters of 30 to 800 nm were synthesized, and the surfaces of the silica nanoparticles were functionalized with TAT peptides or 3-aminopropyltriethoxysilane (APTES). Confocal microscopy and flow cytometry were used to determine the cellular locations and the uptake efficiencies of positively-charged silica nanoparticles (APTES- and TAT-) of various sizes from 30 to 800 nm. The cellular uptake efficiencies of all the differently-sized particles were significantly increased in the presence of TAT peptides. On the basis of an efficient TAT-mediated delivery system, we were able to show that TAT peptides could be used as effective cellular-uptake reagents, particularly for large particles.

Active digital microfluidic paper chips with inkjet-printed patterned electrodes.

Active, paper-based, microfluidic chips driven by electrowetting are fabricated and demonstrated for reagent transport and mixing. Instead of using the passive capillary force on the pulp to actuate a flow of a liquid, a group of digital drops are transported along programmed trajectories above the electrodes printed on low-cost paper, which should allow point-of-care production and diagnostic activities in the future.

Actuation of digital micro drops by electrowetting on open microfluidic chips fabricated in photolithography.

Basic manipulations of discrete liquid drops on opened microfluidic chips based on electrowetting on dielectrics were described. While most developed microfluidic chips are closed systems equipped with a top plate to cover mechanically and to contact electrically to drop samples, our chips are opened systems with a single plate without any electric contact to drops directly. The chips consist of a linear array of patterned electrodes at 1.8 mm pitch was fabricated on a glass plate coated with thin hydrophobic and dielectric layers by using various methods including photolithography, spin coating and ion sputtering. Several actuations such as lateral oscillation, colliding mergence and translational motion for 3-10 µL water drops have been demonstrated satisfactory. All these kinetic performances of opened chips were similar to those of closed chip systems, indicating superiority of a none-contact method for the transport of drops on opened microfluidic chips actuated by using electrowetting technique.

Patterning of gold nanoparticles on fluoropolymer films by using patterned surface grafting and layer-by-layer deposition techniques.

The patterning of gold nanoparticles (GNPs) on the surface of a fluoropolymer substrate by using patterned surface grafting and layer-by-layer deposition techniques is described. The surface of a poly(tetrafluoroethylene-co-perfluorovinyl ether) (PFA) substrate was selectively implanted with 150 keV proton ions. Peroxide groups were successfully formed on the implanted PFA surface, and their concentration depended on the fluence. Acrylic acid was graft polymerized onto the implanted regions of the PFA substrate, resulting in well-defined patterns of poly(acrylic acid) (PAA) on the PFA substrate. The surface properties of the PAA-patterned PFA surface, such as chemical compositions, wettability, and morphology, were investigated. The surface analysis results revealed that PAA was definitely present on the implanted regions of the PFA surface, and the degree of grafting was dependent on three factors: fluence, grafting time, and monomer concentration. Furthermore, GNP patterns were generated on the prepared PAA-patterned PFA surface by layer-by-layer deposition of GNPs and poly(diallyldimethyl ammonium chloride). The multilayers of GNPs were deposited only onto the PAA-grafted regions separated by bare PFA regions, and the resulting GNP patterns exhibited good electrical conductivity.