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Abstract Properly handling animals and understanding their habits are crucial to establish a society where humans and animals coexist. Thus, identifying individual animals, including their possessions, and adequately managing each animal is necessary. Although several conventional identification methods exist, such as the use of ear punch, tattoos, and radio frequency (RF) chips, they require several processes and external apparatus. In this study, we proposed a new biotagging method using a microneedle array for animal identification. Our approach uses dissolvable microneedle arrays as a single patch to deliver dyes directly into the skin layer. Additionally, we developed a new fabrication method for customised female moulds to realise microneedle array patches (MAPs) with patterns of different characters and number. The characteristics and feasibility of the patterned MAPs were confirmed through basic evaluations and animal experiments. Moreover, we confirmed that patterns formed from biotagging using the developed patterned MAPs lasted over one month with clear readability. Finally, we confirmed that our patterned MAPs successfully realised biotagging on rat skin with the designated patterns including characters and number patterns. The proposed method is expected to enable minimally invasive tagging without external equipment or complex processes. In addition, the developed method could be used to embed various tags into the skin of animals and humans in the future.

Photothermolysis is the process that converts radiation energy into thermal energy, which results in the destruction of surrounding tissues or cells through thermal diffusion. Laser therapy that is based on photothermolysis has been a widely used treatment for various skin diseases such as skin cancers and port-wine stains. It offers several benefits such as non-invasiveness and selective treatment. However, the use of light, e.g., laser, for safe and effective photothermolysis becomes challenging due to the limited penetration of light into skin tissue as well as the presence of melanin, which absorbs this light. To solve the current issues, we propose an optical microneedle–lens array (OMLA) coated with gold in this work to directly deliver light to targeted skin layers without being absorbed by surrounding tissues as well as melanin, which results in the improvement of the efficiency of photothermal therapy. We developed a novel fabrication method, frame-guided micromolding, to prepare the OMLA by assembling two negative molds with simultaneous alignment. In addition, evaluations of the optical and heat transfer characteristics of the OMLA were performed. We expect our developed OMLA to play a crucial role in realizing more effective laser therapy by allowing the precise delivery of photons to the target area.

Abstract Infectious diseases are among the leading causes of mortality worldwide. A new coronavirus named severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) was identified in Wuhan, China in 2019, and the World Health Organization (WHO) declared its outbreak, coronavirus disease 2019 (COVID-19), as a global pandemic in 2020. COVID-19 can spread quickly from person to person. One of the most challenging issues is to identify the infected individuals and prevent potential spread of SARS-CoV-2. Recently, anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody tests using immunochromatographic methods have been used as a complement to current detection methods and have provided information of the approximate course of COVID-19 infection. However, blood sampling causes pain and poses risks of infection at the needle puncture site. In this study, a novel patch sensor integrating porous microneedles and an immunochromatographic assay (PMNIA) was developed for the rapid detection of anti-SARS-CoV-2 IgM/IgG in dermal interstitial fluid (ISF), which is a rich source of protein biomarkers, such as antibodies. Biodegradable porous microneedles (MNs) made of polylactic acid were fabricated to extract ISF from human skin by capillary effect. The extracted ISF was vertically transported and flowed into the affixed immunoassay biosensor, where specific antibodies could be detected colorimetrically on-site. Anti-SARS-CoV-2 IgM/IgG antibodies were simultaneously detected within 3 min in vitro. Moreover, the limit of detection of anti-SARS-CoV-2 IgM and IgG concentrations was as low as 3 and 7 ng/mL, respectively. The developed device integrating porous MNs and immunochromatographic biosensors is expected to enable minimally invasive, simple, and rapid anti-SARS-CoV-2 IgM/IgG antibody testing. Furthermore, the compact size of the MN and biosensor-integrated device is advantageous for its widespread use. The proposed device has great potential for rapid screening of various infectious diseases in addition to COVID-19 as an effective complementary method with other diagnostic tests.

Abstract A microneedle (MN) array is a novel biomedical device adopted in medical applications to pierce through the stratum corneum while targeting the viable epidermis and dermis layers of the skin. Owing to their micron-scale dimensions, MNs can minimize stimulations of the sensory nerve fibers in the dermis layer. For medical applications, such as wound healing, biosensing, and drug delivery, the structure of MNs significantly influences their mechanical properties. Among the various microfabrication methods for MNs, fused deposition modeling (FDM), a commercial 3D printing method, shows potential in terms of the biocompatibility of the printed material (polylactic acid (PLA)) and preprogrammable arbitrary shapes. Owing to the current limitations of FDM printer resolution, conventional micron-scale MN structures cannot be fabricated without a post-fabrication process. Hydrolysis in an alkaline solution is a feasible approach for reducing the size of PLA needles printed via FDM. Moreover, weak bonding between PLA layers during additive manufacturing triggers the detachment of PLA needles before etching to the expected sizes. Furthermore, various parameters for the fabrication of PLA MNs with FDM have yet to be sufficiently optimized. In this study, the thermal parameters of the FDM printing process, including the nozzle and printing stage temperatures, were investigated to bolster the interfacial bonding between PLA layers. Reinforced bonding was demonstrated to address the detachment challenges faced by PLA MNs during the chemical etching process. Furthermore, chemical etching parameters, including the etchant concentration, environmental temperature, and stirring speed of the etchant, were studied to determine the optimal etching ratio. To develop a universal methodology for the batch fabrication of biodegradable MNs, this study is expected to optimize the conditions of the FDM-based fabrication process. Additive manufacturing was employed to produce MNs with preprogrammed structures. Inclined MNs were successfully fabricated by FDM printing with chemical etching. This geometrical structure can be adopted to enhance adhesion to the skin layer. Our study provides a useful method for fabricating MN structures for various biomedical applications.

Abstract With the rapid development of the Internet of Things (IoT) and the emergence of 5G, traditional silicon-based electronics no longer fully meet market demands such as nonplanar application scenarios due to mechanical mismatch. This provides unprecedented opportunities for flexible electronics that bypass the physical rigidity through the introduction of flexible materials. In recent decades, biological materials with outstanding biocompatibility and biodegradability, which are considered some of the most promising candidates for next-generation flexible electronics, have received increasing attention, e.g., silk fibroin, cellulose, pectin, chitosan, and melanin. Among them, silk fibroin presents greater superiorities in biocompatibility and biodegradability, and moreover, it also possesses a variety of attractive properties, such as adjustable water solubility, remarkable optical transmittance, high mechanical robustness, light weight, and ease of processing, which are partially or even completely lacking in other biological materials. Therefore, silk fibroin has been widely used as fundamental components for the construction of biocompatible flexible electronics, particularly for wearable and implantable devices. Furthermore, in recent years, more attention has been paid to the investigation of the functional characteristics of silk fibroin, such as the dielectric properties, piezoelectric properties, strong ability to lose electrons, and sensitivity to environmental variables. Here, this paper not only reviews the preparation technologies for various forms of silk fibroin and the recent progress in the use of silk fibroin as a fundamental material but also focuses on the recent advanced works in which silk fibroin serves as functional components. Additionally, the challenges and future development of silk fibroin-based flexible electronics are summarized. (1) This review focuses on silk fibroin serving as active functional components to construct flexible electronics. (2) Recent representative reports on flexible electronic devices that applied silk fibroin as fundamental supporting components are summarized. (3) This review summarizes the current typical silk fibroin-based materials and the corresponding advanced preparation technologies. (4) The current challenges and future development of silk fibroin-based flexible electronic devices are analyzed.

Pressure ulcer is a disease that has been increasing rapidly worldwide in recent years following the growing elderly population. However, its diagnoses and treatments still depend on the naked eye and traditional drug treatments, respectively. In this study, we examined the effects of the pressure ulcer-induced regions based on impedance measurements and skin electrical signals, and its treatment efficacy was verified using photobiomodulation therapy. The light used in this therapy was a light emitting diode light (660 nm), and it was verified to enhance antioxidant capacity in the enzyme-based antioxidation process. An examination of the angiogenesis efficacy based on wound healing activity and tube formation activation at the cell level confirmed that photobiomodulation therapy accelerated wound healing and angiogenesis. When the treatment effect of the therapy was evaluated with a rat animal model of pressure ulcer, the region affected by the pressure ulcer and the infiltration of inflammatory cells were significantly reduced by photobiomodulation therapy. The diagnosis using skin impedance measurement showed differences in the region affected by the pressure ulcer. The results of this study confirmed the diagnosis based on the impedance and treatment efficacy of photobiomodulation therapy and the treatment of pressure ulcer. The use of photobiomodulation therapy in conjunction with the existing treatment methods is expected to improve the efficiency of the pressure ulcer treatment.

Abstract To pierce through the skin and interact with the first biofluid available, microneedles should be mechanically strong. However, some polymers used to fabricate microneedles yield insufficient strength for the fabrication of arrays (PDMS, highly porous structures, etc.). To enhance mechanical properties, piercing materials can be used. They aim to pierce the skin evenly and dissolve quickly, clearing the way for underlying microneedles to interact with the interstitial fluid (ISF). Three materials—carboxymethyl cellulose (CMC), alginate, and hyaluronic acid (HA)—are discussed in this article. Low concentrations, for a quick dissolution while keeping enhancing effect, are used ranging from 1–5%(w/w) in deionized water. Their overall aspects, such as geometrical parameters (tip width, height, and width), piercing capabilities, and dissolution time, are measured and discussed. For breaking the skin barrier, two key parameters—a sharp tip and overall mechanical strength—are highlighted. Each material fails the piercing test at a concentration of 1%(w/w). Concentrations of 3%(w/w) and of 5%(w/w) are giving strong arrays able to pierce the skin. For the purpose of this study, HA at a concentration of 3%(w/w) results in arrays composed of microneedles with a tip width of 48 ± 8 μm and pierced through the foil with a dissolution time of less than 2 min.

Abstract Microneedles (MNs) have been established as promising medical devices as they are minimally invasive, cause less pain, and can be utilized for self-administration of drugs by patients. There has been rapid development in MNs for transdermal monitoring and diagnostic systems, following the active research on fabrication methods and applications for drug delivery. In this paper, recent investigations on bio-sensing using MNs are reviewed in terms of the applicability to continuous glucose monitoring system (CGMS), which is one of the main research focuses of medical engineering technologies. The trend of the functionalized MNs can be categorized as follows: (i) as a sensing probe, and (ii) as a biological fluid collector. MNs as in vivo sensors are mainly integrated or coated with conductive materials to have the function as electrodes. MNs as fluid collectors are given a certain geometrical design, such as a hollow and porous structure aided by a capillary action or negative pressure, to extract the interstitial fluids or blood for ex vivo analysis. For realization of CGMS with MNs, a long-term accurate measurement by the MN-based sensing probe or a fluidic connection between the MN-based fluid collector and the existing microfluidic measurement systems should be investigated.

Unmanned Aerial Vehicles (UAVs) are abundantly becoming a part of society, which is a trend that is expected to grow even further. The quadrotor is one of the drone technologies that is applicable in many sectors and in both military and civilian activities, with some applications requiring autonomous flight. However, stability, path planning, and control remain significant challenges in autonomous quadrotor flights. Traditional control algorithms, such as proportional-integral-derivative (PID), have deficiencies, especially in tuning. Recently, machine learning has received great attention in flying UAVs to desired positions autonomously. In this work, we configure the quadrotor to fly autonomously by using agents (the machine learning schemes being used to fly the quadrotor autonomously) to learn about the virtual physical environment. The quadrotor will fly from an initial to a desired position. When the agent brings the quadrotor closer to the desired position, it is rewarded; otherwise, it is punished. Two reinforcement learning models, Q-learning and SARSA, and a deep learning deep Q-network network are used as agents. The simulation is conducted by integrating the robot operating system (ROS) and Gazebo, which allowed for the implementation of the learning algorithms and the physical environment, respectively. The result has shown that the Deep Q-network network with Adadelta optimizer is the best setting to fly the quadrotor from the initial to desired position.

Inhibition of H3N2 influenza PA endonuclease activity by a panel of anionic calix[n]arenes and β-cyclodextrin sulfate has been studied. The joint experimental and theoretical results reveal that the larger, more flexible and highly water-soluble sulfonato-calix[n]arenes have high inhibitory activity, with para-sulfonato-calix[8]arene, SC8, having an IC50 value of 6.4 μM. Molecular docking calculations show the SC8 can interact at both the polyanion binding site and also the catalytic site of H3N2 influenza PA endonuclease.

3D printing is attracting considerable interest for its capacity to produce prototypes and small production runs rapidly. Fused deposit modeling (FDM) was used to produce polyvalent test plates for investigation of the physical, chemical, and in-vitro biological properties of printed materials. The polyvalent test plates (PVTPs) are poly-lactic acid cylinders, 14 mm in diameter and 3 mm in height. The polymer ester backbone was surface modified by a series of ramified and linear oligoamines to increase its hydrophilicity and introduce a positive charge. The chemical modification was verified by FT-IR spectroscopy, showing the introduction of amide and amine functions, and contact angle measurements confirmed increased hydrophilicity. Morphology studies (SEM, optical microscopy) indicated that the modification of PVTP possessed a planar morphology with small pits. Positron annihilation lifetime spectroscopy demonstrated that the polymeric free volume decreased on modification. An MTT-based prolonged cytotoxicity test using Caco-2 cells showed that the PVTPs are non-toxic at the cellular level. The presence of surface oligoamines on the PVTPs reduced biofilm formation by Candida albicans SC5314 significantly. The results demonstrate that 3D printed objects may be modified at their surface by a simple amidation reaction, resulting in a reduced propensity for biofilm colonization and cellular toxicity.

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The anionic calixarenes para-sulphonatocalix[4]arene and 1,3-di-Ophosphonatocalix[ 4]arene, have been used to cap silver nanoparticles. The binding of these functional particles with regard to various serum albumins (bovine serum albumin, human serum albumin, porcine serum albumin and sheep serum albumin) has been studied by variable temperature fluorescence spectroscopy. The quenching of the fluorescence of the proteins was shown to vary as a function of the anionic calixarene capping molecule and also as a function of the origin of the serum albumin. It is thus possible to discriminate between the different species.

Prolonged monitoring by cardiac electrocardiogram (ECG) sensors is useful for patients with emergency heart conditions. However, implant monitoring systems are limited by lack of tissue biocompatibility. Here, we developed an implantable ECG sensor for real-time monitoring of ventricular fibrillation and evaluated its biocompatibility using an animal model. The implantable sensor comprised transplant sensors with two electrodes, a wireless power transmission system, and a monitoring system. The sensor was inserted into the subcutaneous tissue of the abdominal area and operated for 1 h/day for 5 days using a wireless power system. Importantly, the sensor was encapsulated by subcutaneous tissue and induced angiogenesis, inflammation, and phagocytosis. In addition, we observed that the levels of inflammation-related markers increased with wireless-powered transmission via the ECG sensor; in particular, levels of the Th-1 cytokine interleukin-12 were significantly increased. The results showed that induced tissue damage was associated with the use of wireless-powered sensors. We also investigated research strategies for the prevention of adverse effects caused by lack of tissue biocompatibility of a wireless-powered ECG monitoring system and provided information on the clinical applications of inflammatory reactions in implant treatment using the wireless-powered transmission system.

Alpha-melanocyte stimulating hormone (α-MSH) is a highly conserved 13-aa neuropeptide derived from pro-opiomelanocortin by post-translational processing, which has been reported to exhibit potent anti-inflammatory activity and a wide range of immunosuppressive activities in the skin. However, the regulatory effect of α-MSH is not completely clear in cutaneous innate immunity. In this study, we investigate the functional regulation of α-MSH in TLR2-mediated inflammatory responses in normal human keratinocytes (HKs). α-MSH pretreatment down-regulated the Staphylococcus aureus LTA-induced expression of both TLR2 and IL-8 as well as NF-κB nuclear translocation in HK cells. The inhibitory effect of α-MSH was blocked by agouti signaling protein (ASP), an α-MSH receptor-1 antagonist. To investigate the mechanism of this response in more detail, siRNA of IRAK-M, a negative regulator of TLR signaling, was utilized in these studies. The α-MSH suppressive effect on IL-8 production and NF-κB transactivation was inhibited by IRAK-M siRNA transfection in HK cells. These results indicate that α-MSH is capable of suppressing keratinocyte TLR2-mediated inflammatory responses induced by S. aureus-LTA, thus demonstrating another novel immunomodulatory activity of α-MSH in normal human keratinocytes.

A series of six anionic calix[4]arenes, having sulphonate, carboxylate, or phosphonate functions at either the para-aromatic position or the phenolic face were used to cap silver nanoparticles. Their molecular recognition properties were studied with regard to three active pharmaceutical ingredients, chlorhexidine, chloramphenicol, and. gentamycin sulfate. Of these APIs chlorhexidine is known to form cocrystals with the anionic calix[4]arenes, gentamicin sulfate is an aminoglycosidic antibiotic, and chloramphenicol is a neutral antibiotic. As expected the former two APIs show clear complexation behavior as demonstrated by shifts in the visible spectra whereas the last shows no modification in the wavelength of the plasmon resonance of the silver nanoparticles.