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Zika virus (ZIKV) infections are spreading silently with limited global surveillance in at least 89 countries and territories. There is a pressing need to develop an effective vaccine suitable for equitable distribution globally. Consequently, we previously developed a proprietary DNA vaccine encoding secreted non-structural protein 1 of ZIKV (pVAX-tpaNS1) to elicit rapid protection in a T cell-dependent manner in mice. In the current study, we evaluated the stability, efficacy, and immunogenicity of delivering this DNA vaccine into the skin using a clinically effective and proprietary high-density microarray patch (HD-MAP). Dry-coating of pVAX-tpaNS1 on the HD-MAP device resulted in no loss of vaccine stability at 40°C storage over the course of 28 days. Vaccination of mice (BALB/c) with the HD-MAP-coated pVAX-tpaNS1 elicited a robust anti-NS1 IgG response in both the cervicovaginal mucosa and systemically and afforded protection against live ZIKV challenge. Furthermore, the vaccination elicited a significantly higher magnitude and broader NS1-specific T helper and cytotoxic T cell response in vivo compared with traditional needle and syringe intradermal vaccination. Overall, the study highlights distinctive immunological advantages coupled with an excellent thermostability profile of using the HD-MAP device to deliver a novel ZIKV DNA vaccine.

Although metal‐organic framework (MOF)‐derived nanoporous C (NPC) materials offer several advantages for electrochemical sensor applications, surface functionalization and porosity tuning can affect sensor performance. This study presents the development of a skin patch for perspiration and electrocardiogram (ECG) monitoring, leveraging the unique properties of MOF‐on‐MOF‐derived surface‐functionalized hybrid nanoporous C (f‐HNPC) incorporated into laser‐scribed graphene (LSG). Hydroxyl (OH) group‐functionalized NPC, achieved through KOH activation, facilitates electron transport at the electrode–electrolyte interface. This enhances the electrochemical activity, thereby improving sensor sensitivity and expanding the detection range. The integration of f‐HNPC provides enhanced surface area and electrochemical properties, enabling sensitive and selective detection of sweat biomarkers, including glucose (103 µA mM−1 cm−2) and uric acid (184 µA mM−1 cm−2) along with an ultra‐wide glucose detection range (up to 41.5 mM). Moreover, the incorporation of LSG ensures excellent mechanical flexibility, facilitating conformal contact with the skin for reliable signal acquisition. The proposed skin patch demonstrates promising performance in real‐time perspiration analysis and ECG monitoring with a signal‐to‐noise ratio of 23.63 dB, along with high stability and long‐term durability. The synergistic combination of f‐HNPC and LSG shows great potential for developing advanced wearable biosensing platforms for personalized healthcare applications. [ABSTRACT FROM AUTHOR]

DBV712 250 µg (also referred to as Viaskin Peanut or peanut patch; Viaskin is a trademark of DBV Technologies) is an innovative approach to epicutaneous immunotherapy (EPIT). The patch-based technology system facilitates peanut protein (allergen) absorption into the intact non-vascularized epidermis to promote desensitization to peanut while limiting systemic allergen exposure. Efficacy and safety in children have been evaluated in four completed phase 3 studies. Overall, the results from these studies have demonstrated the peanut patch to be superior in desensitization compared with placebo and safe for daily use over multiple years. These findings, as well as supportive evidence from phase 2 studies, confirm the potential for an effective treatment of peanut allergy in children. The purpose of this review is to summarize the safety and efficacy of the peanut patch in the treatment of peanut allergy. [ABSTRACT FROM AUTHOR]

BackgroundTranscutaneous bilirubin (TcB) measurements during and after phototherapy for hyperbilirubinemia must be performed on unexposed skin. There are commercially made skin patches for this purpose, but they are relatively unavailable in low-resource settings. We devised a simple cotton patch and tested its use for TcB during phototherapy.MethodsMeasurements were taken in healthy neonates born at a gestational age of ≥35 weeks who were undergoing phototherapy for hyperbilirubinemia in western India before, 12 h after the start, and 12 h after the end of phototherapy. Total serum bilirubin (TSB) was measured using the diazo method in a clinical laboratory. TcB measurements were performed using a Dräger Jaundice Meter JM-105 placed over the sternum on two skin areas that were protected during and after treatment by a commercial (Philips BilEclipse) or self-made patch comprised of cotton gauze and wool.ResultsIn total, 47 neonates were included in our study. Before phototherapy, TSB and TcB values had a strong correlation (Pearson, r = 0.88), with a mean difference of −1.35 mg/dl. Correlations with TSB were good and equivalent for TcB values measured on skin covered by the commercial and self-made patches during (0.78 and 0.70, respectively) and after (0.57 and 0.58, respectively) phototherapy. TcB values measured on skin covered by the two patches correlated well both during and after phototherapy, with r = 0.82 and 0.90, respectively, and mean (95% confidence interval) differences of −1.21 and −0.32 mg/dl, respectively.ConclusionsReliable TcB measurements taken during and after phototherapy can be achieved on skin covered with a simple and affordable cotton skin patch.

Giant Congenital Melanocytic Naevi (GCMN) is a very rare condition that mostly occurs due to an oncogenic mutation involving the NRAS (neuroblastoma RAS viral oncogene homologue) gene. GCMNs can be clinically diagnosed due to their typical features, but histopathology confirms the diagnosis. GCMN has a high propensity for transforming into malignant melanoma and leptomeningeal melanocytosis, leading to neurological deficits such as epilepsy and neurofibromatosis. As it is associated with Central Nervous System (CNS) melanosis, Magnetic Resonance Imaging (MRI) of the brain and spine is crucial. Here, three cases are reported of the babies born with GCMN from August 2022 to July 2023 in a tertiary care hospital among a total of 11,915 live births, where the incidence is much higher than found in the literature. Present series describes three cases with GCMN, including clinical features, MRI findings, short-term outcomes, risk factors, and modalities of the management. All three cases showed extensive blackish pigmented patches involving most of the body surface and MRI evidence of Neurocutaneous Melanosis (NCM). The third baby succumbed to death due to fulminant sepsis on day 2 of life. Management of GCMN requires a multimodal approach, including medical, surgical, chemotherapeutic, palliative, and psychological support for patients as well as parents, and follow-up is necessary for the early detection of malignant transformation. Detailed knowledge of this very rare condition may enable us to develop newer treatment modalities to achieve better outcomes in the near future.

Background: Skin color and texture play a significant role in influencing impressions. To understand the influence of skin appearance and to develop better makeup products, objective evaluation methods for makeup finish have been explored. This study aims to apply machine learning technology, specifically deep neural network (DNN), to accurately analyze and evaluate delicate and complex cosmetic skin textures. Methods: "Skin patch datasets" were extracted from facial images and used to train a DNN model. The advantages of using skin patches include retaining fine texture, eliminating false correlations from non‐skin features, and enabling visualization of the inferred results for the entire face. The DNN was trained in two ways: a classification task to classify skin attributes and a regression task to predict the visual assessment of experts. The trained DNNs were applied for the evaluation of actual makeup conditions. Results: In the classification task training, skin patch‐based classifiers for age range, presence or absence of base makeup, formulation type (powder/liquid) of the applied base makeup, and immediate/while after makeup application were developed. The trained DNNs on regression task showed high prediction accuracy for the experts' visual assessment. Application of DNN to the evaluation of actual makeup conditions clearly showed appropriate evaluation results in line with the appearance of the makeup finish. Conclusion: The proposed method of using DNNs trained on skin patches effectively evaluates makeup finish. This approach has potential applications in visual science research and cosmetics development. Further studies can explore the analysis of different skin conditions and the development of personalized cosmetics. [ABSTRACT FROM AUTHOR]

Giant Congenital Melanocytic Naevi (GCMN) is a very rare condition that mostly occurs due to an oncogenic mutation involving the NRAS (neuroblastoma RAS viral oncogene homologue) gene. GCMNs can be clinically diagnosed due to their typical features, but histopathology confirms the diagnosis. GCMN has a high propensity for transforming into malignant melanoma and leptomeningeal melanocytosis, leading to neurological deficits such as epilepsy and neurofibromatosis. As it is associated with Central Nervous System (CNS) melanosis, Magnetic Resonance Imaging (MRI) of the brain and spine is crucial. Here, three cases are reported of the babies born with GCMN from August 2022 to July 2023 in a tertiary care hospital among a total of 11,915 live births, where the incidence is much higher than found in the literature. Present series describes three cases with GCMN, including clinical features, MRI findings, short-term outcomes, risk factors, and modalities of the management. All three cases showed extensive blackish pigmented patches involving most of the body surface and MRI evidence of Neurocutaneous Melanosis (NCM). The third baby succumbed to death due to fulminant sepsis on day 2 of life. Management of GCMN requires a multimodal approach, including medical, surgical, chemotherapeutic, palliative, and psychological support for patients as well as parents, and follow-up is necessary for the early detection of malignant transformation. Detailed knowledge of this very rare condition may enable us to develop newer treatment modalities to achieve better outcomes in the near future. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) infections are spreading silently with limited global surveillance in at least 89 countries and territories. There is a pressing need to develop an effective vaccine suitable for equitable distribution globally. Consequently, we previously developed a proprietary DNA vaccine encoding secreted non-structural protein 1 of ZIKV (pVAX-tpaNS1) to elicit rapid protection in a T cell-dependent manner in mice. In the current study, we evaluated the stability, efficacy, and immunogenicity of delivering this DNA vaccine into the skin using a clinically effective and proprietary high-density microarray patch (HD-MAP). Dry-coating of pVAX-tpaNS1 on the HD-MAP device resulted in no loss of vaccine stability at 40°C storage over the course of 28 days. Vaccination of mice (BALB/c) with the HD-MAP-coated pVAX-tpaNS1 elicited a robust anti-NS1 IgG response in both the cervicovaginal mucosa and systemically and afforded protection against live ZIKV challenge. Furthermore, the vaccination elicited a significantly higher magnitude and broader NS1-specific T helper and cytotoxic T cell response in vivo compared with traditional needle and syringe intradermal vaccination. Overall, the study highlights distinctive immunological advantages coupled with an excellent thermostability profile of using the HD-MAP device to deliver a novel ZIKV DNA vaccine.

The development of batch fabrication techniques for flexible skin patches may promote the use of these devices in daily health monitoring and public health crisis. Here, a modularized mass fabrication and selective integration approach that can yield multiparameter electronic skin patches are presented. The screen‐printing technique has been adopted to achieve five modularized sensors for electrocardiogram (ECG), temperature, hydration, blood oxygen, and pH sensing as well as a universal central hub to connect the sensors with external wireless circuits. In a single glass substrate, 13 ECG electrodes, more than 200 sensors, or 80 central hubs can be printed with high homogeneity in performance. In addition to rapid printing of these components, special temperature‐sensitive paste, batch electropolymerization processes, selection of stress confining substrates, and usage of anisotropic conductive tapes have been investigated to facilitate the integration processes of the multiparameter skin patches. The systematic techniques presented in this paper may help to overcome the bottleneck that is currently constraining the mass fabrication of multiparameter skin patches, allowing rapid deployment and convenient application of these devices for health monitoring in large populations. [ABSTRACT FROM AUTHOR]

• When delivered by VaxiPatch, a 2 µg dose of Flucelvax was comparable to IM injection. • Co-formulation of a low-dose AS01 B -like adjuvant enhanced VaxiPatch responses. • Even for adjuvanted groups, reactogenicity from patch application was negligible. • Vaccine antigens were dramatically stabilized against heat stress on VaxiPatch. All seasonal influenza vaccines for 2021–2022 in the US were quadrivalent and the market continues to be dominated by intramuscular delivery of non-adjuvanted, virion-derived antigens grown in chicken eggs. Up to four new egg-adapted production influenza vaccine strains must be generated each year. The introduction in 2012 of Flucelvax®, which is grown in mammalian suspension cell culture and uses vaccine production strains without adaptive mutations for efficient growth in eggs, represented a major advance in vaccine production technology. Here we demonstrate that Flucelvax can be reformulated and combined with a liposomal adjuvant containing QS-21 (Verndari Adjuvant System 1.1, VAS1.1) or QS-21 and 3D-PHAD (VAS1.2) for intradermal administration using a painless skin patch, VaxiPatch™. VAS1.2 is similar to AS01 B , the adjuvant system used in Shingrix® and Mosquirix™. We show that Flucelvax, when reformulated and concentrated using tangential flow filtration (TFF), maintains hemagglutination and single radial immunodiffusion (SRID) potency. Loading the reformulated Flucelvax material onto VaxiPatch arrays conferred high levels of resistance to heat stress and room temperature stability. TFF enriched vaccine antigens were combined with VAS1.1 or VAS1.2 and dispensed in 10nL drops into the pockets of 36 (total 360 nL) stainless steel microneedles arranged in a microarray 1.2 cm in diameter. Using VaxiPatch delivery of 2 µg of antigen, we demonstrated intramusuclar-comparable IgG and hemagglutination inhibition (HAI) immune responses in Sprague Dawley® rats. With addition of VAS1.2, antigen-specific IgG titers were increased as much as 68-fold (47-fold for VAS1.1) with improvements in seroconversion for three of four strains (all four were improved by VAS1.1). TFF-reformulated antigens combined with VAS1.1 or VAS1.2 and delivered by VaxiPatch showed only minor skin reactogenicity after 1 h and no skin reactogenicity after 24 h. These data indicate that VaxiPatch and the VAS system have the potential to be transformative for vaccine delivery. [ABSTRACT FROM AUTHOR]

Introduction: Knee osteoarthritis is the most common arthritis and musculoskeletal disease. The low efficacy and significant side effects of synthetic drugs in the treatment of this disease have led many researchers to look for a drug that is effective but has fewer side effects. Recently, ginger is one of the most popular herbal remedies in the treatment of this disease. This study aimed to compare the effect of ginger by skin patch and oral capsule on pain intensity, joint dryness, and daily performance of patients with osteoarthritis of the knee. Materials and Methods: This was a three-group clinical trial study that was performed on patients referred to Afshar orthopedic clinic in Dezful in 2015. Sampling was available. Subjects were randomly divided into three groups according to the table of random numbers: skin patch, ginger capsule, and control. All three groups received treatment prescribed by an orthopedic specialist. In addition, the ginger capsule group used 2 500 mg ginger capsules daily and the ginger skin patch group used one ginger skin patch daily in the middle of the waist for 9 weeks. The data collection tool was a demographic questionnaire and a translated version of the Arthritis Index of Western Ontario and McMaster Universities (WOMAC). One-way analysis of variance, paired t-test, and Tukey post hoc test aswas used to analyze the data. A significant level were considered 0.05. Results: The total number of participants in the study was 135.In the groups of ginger capsules, ginger skin patch, and control. the mean pain intensity before the intervention was 13.08, 14.52, and 13.55, respectively, and after the intervention, it decreased to 7.05, 8.62, and 11.37(P<0.00). Conclusion: Ginger in both oral capsules and skin patches is effective in reducing the severity of pain and dysfunction in patients with osteoarthritis of the knee. It seems that only oral capsules reduce joint dryness and the ginger skin patch is ineffective. [ABSTRACT FROM AUTHOR]

3D printing of conductive polymers is an attractive technique for achieving high flexibility, wearability, and sensing characteristics without geometrical limitations. However, there is an urgent need to integrate printability, conductivity, and sensing capability. Herein, a conductive polymer ink for 3D printing that combines the desirable features of high electrical conductivity, flexible stretchability, and strain‐sensing monitoring is prepared. The ink matrix is polydimethylsiloxane and synergistically enhanced by acetylene carbon black (ACB) and multi‐walled carbon nanotubes (MWCNTs) (silane or un‐silane‐modified). The inks are screened step‐by‐step to explore their printability, rheology, mechanical properties, and electrical performance upon loading. The formation of an electrically conductive network, electrical properties upon tensile load, and strain sensing stability under cyclic stretching are investigated intensively. It is demonstrated that conductive polymers filled by ACB and silane‐modified, MWCNTs (MWCNTs‐MTES) possess superior printability, stretchability, conductivity, and strain sensing behaviors. Finally, a flexible wearable strain‐sensing skin patch is printed, and it successfully records joint motion signals on human fingers, wrists, and elbows with good stability and repeatability. Those results show the extent of potential applications in healthcare and motion monitoring fields. This work provides an efficient and simple route to achieve comfortably wearable and high‐performance strain sensors. [ABSTRACT FROM AUTHOR]

Advances in flexible and hybrid electronics promote increasing demands for wearable sensors in personal health, monitoring, and diagnostic medical gadgets. Conventional wearable devices rely on electronics based on rigid substrates and components with limited conformity to user skin. In this work, we report a fully integrated, stretchable wireless electrocardiography (ECG) system developed on highly elastic, ultra-thin (100 μm) thermoplastic polyurethane (TPU) film without any rigid or flexible interposer. Moreover, the circuit layout printing and component assembly are carried out through sheet-to-sheet (S2S) process directly on TPU film. This study utilizes both experimental reliability tests coupled with data acquired from finite element modeling (FEM) to assess performance and failure of the device under tensile loading. In such a complex system assembly, FEM simulation not only provides insights on the overall electromechanical performance of the device, but also facilitates localization of the failure points which are difficult to access for visual inspection. The performance of the device is also evaluated through controlled uniaxial cyclic strain at 5% and 10% elongation. The durability test shows that the assembled device can stay functional over hundreds of deformation cycles, suggesting that direct assembly of conventional components on stretchable substrate represents a promising approach for fully integrated stretchable devices, which is a step toward scalable manufacture of wearable stretchable electronics through high-throughput manufacturing processes. [ABSTRACT FROM AUTHOR]

Wearable biosensors are considered to be a promising technology that revolutionizes conventional health monitoring methods as it is able to provide precautions when potential health problem is detected. However, the current fatigue-monitoring methods are still using either invasive blood tests or bulky inconvenient devices. Herein, we present a new skin patch sensor based on porous Ultra-High-Molecular-Weight Polyethylene (UHMWPE) nanomembranes which tracks muscle fatigue through sweat biomarkers, particularly cortisol hormone. By having nano-level thickness (i.e. around 100nm), the sweat sensor is able to conform perfectly to human skin without the necessity of any adhesives. We used Raman spectroscopy to analyze the sweat cortisol in the skin patch, established the calibration curve for both qualitative and quantitative characterization of sweat cortisol level change and validated the measurements with the blood samples collected at the same exercise intensity. From our experimental data, it is concluded that the cortisol level increases as the exercise intensity are increased and a strong correlation between the sweat cortisol and blood cortisol has been proven, demonstrating the patch’s ability to detect sweat cortisol which acts as a strong indicator of sports fatigue level. Our developed UHMWPE membrane opens up a large opportunity for developing a one-of-a-kind sweat sensor by further integrating it with flexible electronics for signal processing and real-time transmission in future work. [ABSTRACT FROM AUTHOR]

Objectives: To follow up with a survey for the safety and performance of the coherent biomodulator patch as a device for tinnitus when in clinical use. Materials and methods: A survey with 20 questions was emailed to device users a few weeks after fulfilled treatment. Collected data from 927 responders from February 2017 to July 2020 was exported and analyzed. The treatment time was 3 weeks, and the patches were changed daily and placed behind one year. The analysis was performed in order to investigate the possibility of subgroups and if the effect of one or more treatments are different, and is the relief dependent on how long the users have had troublesome tinnitus, the age of the user, and the severity of the tinnitus. Results: Most users were 45 years and older with a gender ratio of 1.65 men vs women. In general, the users reported highly bothersome tinnitus with 82% answering frequently to a lot before treatment. This follow up survey showed that 33% experienced any kind of improvement. The majority of those that reported improvement came from the subgroup of 4-10 years suffered from tinnitus. A very low frequency of side-effects was reported with no new risks or unexpected issues. Conclusion: When considering the intended purpose of the steady state coherent biomodulator and the provided information in this survey, the device remains suitable for the intended tinnitus users. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery (TDD) is an alternative method of drug administration for drugs whose delivery by conventional oral, topical, intravenous and intramuscular methods is of limited efficacy. Recent advances in TDD involve the use of nanoparticles (NPs), which exhibit a great potential to enhance drug permeation across the skin. NPs can also provide controlled release, the ability to deliver both hydrophilic and hydrophobic drugs and reduce side effects, and when used in a TDD method they are also non-invasive. Another developing technology for TDD employs skin patches containing microneedles. Microneedles represent a painless and minimally invasive method of TDD in which micron-sized pores are created in the epidermis to allow delivery of drugs to the blood vessels present in the dermal layer of the skin. New researches have focussed on combining different TDD approaches to overcome previous constraints of drug delivery via conventional methods. [ABSTRACT FROM AUTHOR]

Lack of adherence to medication dosing schedules is a significant cause of morbidity and mortality with large associated financial costs. This is especially true for contraceptive hormones, which provide almost perfect prevention of pregnancy when used correctly, but have significant failure rates in typical use, due largely to poor adherence. To increase medication acceptability and adherence, we introduce pharmaceutical jewelry, in which a transdermal patch is incorporated into jewelry worn on skin. To demonstrate the approach, we incorporated transdermal patches containing the contraceptive hormone levonorgestrel (LNG) into an earring, a ring, a necklace, and a wrist watch. Transdermal delivery of LNG from earring patches across porcine skin ex vivo achieved a steady state flux of 1.7 μg/cm2·h. Pharmacokinetic analysis in hairless rats yielded LNG delivery rates that maintained serum LNG levels near 1500 pg/ml throughout the 1-week patch application period, which is well above the human contraceptive threshold concentration of 200 pg/ml. When patches were applied cyclically for 16 h on and 8 h off to simulate earring removal at night, serum LNG concentrations dipped during off periods, but remained well above the human contraceptive threshold. Earring patches were well tolerated by the rats. We conclude that pharmaceutical jewelry can provide a novel method of drug delivery, especially for contraceptive hormones, that has the potential to improve acceptability and increase medication adherence. Unlabelled Image [ABSTRACT FROM AUTHOR]

The short lifetime and low sensitivity of the current glucose electrochemical sensors are two major issues for implementing continuous real-time monitoring of glucose in vivo. Here we show that a unique microneedle-based glucose monitoring skin patch (termed here MGMSP) can continuously measure glucose in real time in live animals with micromolar sensitivity and over 14 days of service life. This MGMSP employs a glucose oxidase (GOD) and carbon nanotube (CNT) modified hollow syringe as electrochemical sensor for glucose monitoring, an integrated circuit for signal processing and transmission, and the real-time glucose levels are displayed on smartphone via Bluetooth. The designed microneedle device protects the stability of the sensing molecules immobilized within the inner surface of hollow syringe and simultaneously the interior space of hollow syringe substantially increases the amount of immobilized sensing molecules. This microneedle design thus extends the lifetime as well as improves the detection sensitivity. The final MGMSP enables the continuous real-time monitoring of glucose in the interstitial fluid of live rats. This innovative microneedle-based MGMSP could potentially provide the public with high-accuracy continual glucose monitoring. [ABSTRACT FROM AUTHOR]

Abstract A totally organic and disposable electrochromic timer integrated with an enzymatic electrode and powered by biofuel cells is developed. The cathode of the self-powered electrochromic timer consists of a composite electrochromic film of poly(3,4-ethylenedioxythiophene) (PEDOT) and polyurethane (PU), while the anode is made up of a fructose dehydrogenase (FDH) enzymatic electrode. The electrochromic changes over time (up to 100 min) can be displayed in the device, and the speed of color change can be controlled by changing the resistance between the anode and the cathode. Automatic activation of the timer after placement on a skin is achieved by integrating a porous microneedle array. The electrochromic timer would be used along with a skin patch as a time-lapse display of medical and cosmetic treatments. Highlights • A totally organic and disposable electrochromic timer driven by enzymatic electrode reaction was developed. • The ability to function as a timer for skin patch was demonstrated. • The patch combined with a porous microneedle array served as the automatic activation switch that closes the transdermal electric circuit after it is applied to the skin surface. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate a non-energy consuming light bio-modulator patch creating coherency for tinnitus relief. Materials and Methods: Three independent clinical studies and continuous post market clinical follow up have been performed during the year 2012 to 2018. The first study was a limited interventional investigation with 10 patients, the second was a larger interventional study with finally 48 patients further investigated, and the third a randomized, placebo-controlled, double-blind study with 82 patients. In the clinical studies patch performance evaluated with questionnaires related to tinnitus, quality-of-life, and safety were assessed prior, during and after the end of treatment. In all studies the treatment time was 3 weeks and the patches were placed behind one year. Results: The first study indicated a relief with half of the patients at the end of the treatment. Still two years after the study one third reported tinnitus relief. However, the numbers of patients were low. The second study showed a responder relief in 58% directly after end of treatment and 60% one month after. The third study showed that the biomodulator patch had statistical significant three times more responders than placebo one month after end of treatment, measured as a decrease from baseline in at least 2 points in tinnitus annoyance visual analogue scale as a minimal clinical significant difference. Tinnitus handicap inventory was improved by mean-16 points significantly for the active responder group, but with no statistically significant changes for the placebo group or between the groups. The biomodulator patch was safe and well-tolerated in all three studies. The post market clinical follow up has shown a 30% reported relief and with no new risks or unexpected issues affecting the effectiveness or safety. Conclusion: Taken under consideration the lack of easy-to-use alternative and the low risk profile, this patch device could highly be recommended to try for tinnitus relief as a conclusion based on the clinical studies and post market surveys. Further studies of how this bio-modulator more specific act on the auditory system, how long this may sustain and if there can be subgroups of patients or variations in the treatment time, delayed onset, number of patches, and frequency for more efficiency needs to be considered. [ABSTRACT FROM AUTHOR]

Our artificial bioinspired adhesive patch is inspired by two different biological creatures in one design, which consists of a densely packed hexagonal tree-frog pad embedded with vulgaris octopuses' microscopic suckers. This work focuses on the creation of a new microscopic sucker design that takes inspiration from the structure of real octopus' suckers to improve adhesion and overcome potential issues related to the existing micro-sucker design. Theoretical analysis, simulations, and experimental studies demonstrated that this new-designed microscopic sucker exhibits robust adhesion under various conditions (dry, moist, underwater, and under oil). Several factors that influence adhesion performance, including compressive preloading force, time of attachment, number of contact cycles, and surface roughness, are investigated. It showed stronger adhesion than previous sucker designs and proved its ability to remain attached for up to 24 h, withstand a large number of contact cycles, and adhere to high- and low-roughness surfaces. It reached 57.3–116.4 kPa of normal adhesion strength and 29.8–93.47 kPa of shear adhesion strength. Based on these results, our adhesive patch design could pave the way for future skin-conforming patches in medical devices. [ABSTRACT FROM AUTHOR]

We present a reusable and porous skin patch (RPS patch) capable of controlling adhesion force with a thermal-pneumatic method for repetitive use as well as improving moisture permeability for long-term use without skin troubles. Previous skin patches cause skin troubles due to high adhesion force (∼30 kPa) and low moisture permeability (∼382 g/m 2 /day), hindering them from repeatable and long-term use. We control the skin adhesion force of the RPS patch using thermopneumatic pressure generated by an embedded heater on multiple chamber arrays. The RPS patch controls the adhesion force ranging from 8 to 29 kPa on both dry and wet skin while keeping the stable adhesion force for 48 h. It shows repeatable adhesion up to 100 times, and the adhesion force is restored after the RPS patch is washed with water, thus enabling repetitive skin adhesion. We improve the moisture permeability of the RPS patch to 733 g/m 2 /day while maintaining the adhesion force by making the RPS patch with porous materials. The RPS patch shows no skin troubles for 7 days of attachment, thereby being available for long-term skin attachment. The RPS patch, having adhesion control capability and high moisture permeability, shows potential for use in daily life in biomedical applications, including wearable sensors, medical adhesives, and rehabilitation robots.

Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the Center for Disease control (CDC) recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell-based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an enzyme immunosorbent assay (ELISA) and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell-based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at the end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.