Multifunctional Injectable Hydrogel for In Vivo Diagnostic and Therapeutic Applications.

Injectable hydrogels show high potential for in vivo biomedical applications owing to their distinctive mode of administration into the human body. In this study, we propose a material design strategy for developing a multifunctional injectable hydrogel with good adhesiveness, stretchability, and bioresorbability. Its multifunctionality, whereupon multiple reactions occur simultaneously during its injection into the body without requiring energy stimuli and/or additives, was realized through meticulous engineering of bioresorbable precursors based on hydrogel chemistry. The multifunctional injectable hydrogel can be administered through a minimally invasive procedure, form a conformal adhesive interface with the target tissue, dynamically stretch along with the organ motions with minimal mechanical constraints, and be resorbed in vivo after a specific period. Further, the incorporation of functional nanomaterials into the hydrogel allows for various in vivo diagnostic and therapeutic applications, without compromising the original multifunctionality of the hydrogel. These features are verified through theranostic case studies on representative organs, including the skin, liver, heart, and bladder.

Soft Bioelectronics Based on Nanomaterials.

Recent advances in nanostructured materials and unconventional device designs have transformed the bioelectronics from a rigid and bulky form into a soft and ultrathin form and brought enormous advantages to the bioelectronics. For example, mechanical deformability of the soft bioelectronics and thus its conformal contact onto soft curved organs such as brain, heart, and skin have allowed researchers to measure high-quality biosignals, deliver real-time feedback treatments, and lower long-term side-effects in vivo. Here, we review various materials, fabrication methods, and device strategies for flexible and stretchable electronics, especially focusing on soft biointegrated electronics using nanomaterials and their composites. First, we summarize top-down material processing and bottom-up synthesis methods of various nanomaterials. Next, we discuss state-of-the-art technologies for intrinsically stretchable nanocomposites composed of nanostructured materials incorporated in elastomers or hydrogels. We also briefly discuss unconventional device design strategies for soft bioelectronics. Then individual device components for soft bioelectronics, such as biosensing, data storage, display, therapeutic stimulation, and power supply devices, are introduced. Afterward, representative application examples of the soft bioelectronics are described. A brief summary with a discussion on remaining challenges concludes the review.

Highly conductive and elastic nanomembrane for skin electronics.

Skin electronics require stretchable conductors that satisfy metallike conductivity, high stretchability, ultrathin thickness, and facile patternability, but achieving these characteristics simultaneously is challenging. We present a float assembly method to fabricate a nanomembrane that meets all these requirements. The method enables a compact assembly of nanomaterials at the water-oil interface and their partial embedment in an ultrathin elastomer membrane, which can distribute the applied strain in the elastomer membrane and thus lead to a high elasticity even with the high loading of the nanomaterials. Furthermore, the structure allows cold welding and bilayer stacking, resulting in high conductivity. These properties are preserved even after high-resolution patterning by using photolithography. A multifunctional epidermal sensor array can be fabricated with the patterned nanomembranes.

A Biodegradable Secondary Battery and its Biodegradation Mechanism for Eco-Friendly Energy-Storage Systems.

The production of rechargeable batteries is rapidly expanding, and there are going to be new challenges in the near future about how the potential environmental impact caused by the disposal of the large volume of the used batteries can be minimized. Herein, a novel strategy is proposed to address these concerns by applying biodegradable device technology. An eco-friendly and biodegradable sodium-ion secondary battery (SIB) is developed through extensive material screening followed by the synthesis of biodegradable electrodes and their seamless assembly with an unconventional biodegradable separator, electrolyte, and package. Each battery component decomposes in nature into non-toxic compounds or elements via hydrolysis and/or fungal degradation, with all of the biodegradation products naturally abundant and eco-friendly. Detailed biodegradation mechanisms and toxicity influence of each component on living organisms are determined. In addition, this new SIB delivers performance comparable to that of conventional non-degradable SIBs. The strategy and findings suggest a novel eco-friendly biodegradable paradigm for large-scale rechargeable battery systems.

The chemical constituents of ethanolic extract from Stauntonia hexaphylla leaves and their anti-inflammatory effects.

Stauntonia hexaphylla (Lardizabalaceae) is an important medicinal plant in Korea, Japan, and China. Its leaves are used to treat many diseases because of their analgesic, sedative, and diuretic effects; however, there are few reports on their chemical constituents and biological activities. This study divided an ethanol extract into dichloromethane (DCM), ethyl acetate (EtOAc), and water fractions. Bioassay-guided fractionation of the ethanol extracts led to the isolation of seven compounds (1-7). To our knowledge, this is the first report of 1-7 from S. hexaphylla. The anti-inflammatory effects were investigated by suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in Western blots. The ethanol extract (20 µg/mL), DCM fraction (20 µg/mL), and compound 1 (10 µM) decreased COX-2 and iNOS expression significantly in LPS-induced RAW264.7 cells. These results suggest that S. hexaphylla leaves and compound 1 are useful candidates for treating inflammatory and other diseases.

Curved neuromorphic image sensor array using a MoS2-organic heterostructure inspired by the human visual recognition system.

Conventional imaging and recognition systems require an extensive amount of data storage, pre-processing, and chip-to-chip communications as well as aberration-proof light focusing with multiple lenses for recognizing an object from massive optical inputs. This is because separate chips (i.e., flat image sensor array, memory device, and CPU) in conjunction with complicated optics should capture, store, and process massive image information independently. In contrast, human vision employs a highly efficient imaging and recognition process. Here, inspired by the human visual recognition system, we present a novel imaging device for efficient image acquisition and data pre-processing by conferring the neuromorphic data processing function on a curved image sensor array. The curved neuromorphic image sensor array is based on a heterostructure of MoS2 and poly(1,3,5-trimethyl-1,3,5-trivinyl cyclotrisiloxane). The curved neuromorphic image sensor array features photon-triggered synaptic plasticity owing to its quasi-linear time-dependent photocurrent generation and prolonged photocurrent decay, originated from charge trapping in the MoS2-organic vertical stack. The curved neuromorphic image sensor array integrated with a plano-convex lens derives a pre-processed image from a set of noisy optical inputs without redundant data storage, processing, and communications as well as without complex optics. The proposed imaging device can substantially improve efficiency of the image acquisition and recognition process, a step forward to the next generation machine vision.

Sensors in heart-on-a-chip: A review on recent progress.

Drug-induced cardiotoxicity is a major problem in drug discovery. Many approaches to efficient drug screening have been developed, including animal testing in vivo and cell testing in vitro. However, due to intrinsic difference between species, animal-based toxicity testing cannot comprehensively determine the potential side effects in subsequent human clinical trials. Furthermore, conventional in vitro assays are costly and labour-intensive, and require numerous tests. Therefore, it would be necessary to develop heart-on-a-chips made with advanced materials and soft bioelectronic fabrication techniques that offer fast, efficient, and accurate sensing of cardiac cells' behaviors in vitro. In this review, we introduce two key sensing methods in heart-on-a-chip for physical and electrical measurements. First, optical (e.g., direct and calcium imaging, and fluorescent, laser-based, and colorimetric sensing) and electrical (e.g., impedance, strain, and crack sensing) sensors that record the contractility of cardiomyocytes are reviewed. Subsequently, various sensors composed of rigid planar/three-dimensional electrodes, soft/flexible electronics, and nanomaterial-based transistors to monitor extracellular and intracellular electrophysiological potentials are discussed. A brief overview of future technology and comments on the current challenges conclude the review.

Facilitated Transdermal Drug Delivery Using Nanocarriers-Embedded Electroconductive Hydrogel Coupled with Reverse Electrodialysis-Driven Iontophoresis.

We herein developed an iontophoretic transdermal drug delivery system for the effective delivery of electrically mobile drug nanocarriers (DNs). Our system consists of a portable and disposable reverse electrodialysis (RED) battery that generates electric power for iontophoresis through the ionic exchange. In addition, in order to provide a drug reservoir to the RED-driven iontophoretic system, an electroconductive hydrogel composed of polypyrrole-incorporated poly(vinyl alcohol) (PYP) was used. The PYP hydrogel facilitated electron transfer from the RED battery and accelerated the mobility of electrically mobile DNs released from the PYP hydrogel. In this study, we showed that fluconazole- or rosiglitazone-loaded DNs could be functionalized with charge-inducing agents, and DNs with charge modification resulted in facilitated transdermal transport via repulsive RED-driven iontophoresis. In addition, topical application and RED-driven iontophoresis of rosiglitazone-loaded DNs resulted in an effective antiobese condition displaying decreased bodyweight, reduced glucose level, and increased conversion of white adipose tissues to brown adipose tissues in vivo. Consequently, we highlight that this transdermal drug delivery platform would be extensively utilized for delivering diverse therapeutic agents in a noninvasive way.

Interaction Between Smoking Cigarettes and Alcohol Consumption on Sexual Experience in High School Students.

OBJECTIVES: This study aimed to analyze nationwide representative data from the 11th Korean Youth Health Risk Behavior Web-Based Survey to determine whether factors including socio-demographics, smoking and alcohol consumption, were factors related to high school students that had experienced sexual intercourse. METHODS: A total of 33,744 students (17,346 boys and 16,398 girls) in 1st, 2nd, and 3rd grade at high school were analyzed. SPSS complex samples methods were used for analyses. Socio-demographic and health risk behaviors (type of region of residence, family structure, and economic status, student academic achievement, gender, high school grade, pocket money, student smoking, alcohol consumption, and having engaged in sexual intercourse) were considered as independent variables. RESULTS: There were 3.6% of girls and 9.9% of boys in high school that were sexually active. This behavior and the average number of cigarettes smoked daily, and alcohol consumed weekly, represented a dose-response relationship, after considering confounding factors. Compared with students that did not smoke or consume alcohol, smoking 1-9 cigarettes per day and consuming 1-6 cups of alcohol and group "smoking more than 10 cigarettes per day and consuming more than 7 cups of alcohol, had a 5.94 and 22.25 higher risk of having had sexual intercourse, respectively. CONCLUSION: Cigarette smoking and alcohol consumption were associated with an increased likelihood of high school students engaging in sexual intercourse.

Large scale and integrated platform for digital mass culture of anchorage dependent cells.

Industrial applications of anchorage-dependent cells require large-scale cell culture with multifunctional monitoring of culture conditions and control of cell behaviour. Here, we introduce a large-scale, integrated, and smart cell-culture platform (LISCCP) that facilitates digital mass culture of anchorage-dependent cells. LISCCP is devised through large-scale integration of ultrathin sensors and stimulator arrays in multiple layers. LISCCP provides real-time, 3D, and multimodal monitoring and localized control of the cultured cells, which thereby allows minimizing operation labour and maximizing cell culture performance. Wireless integration of multiple LISCCPs across multiple incubators further amplifies the culture scale and enables digital monitoring and local control of numerous culture layers, making the large-scale culture more efficient. Thus, LISCCP can transform conventional labour-intensive and high-cost cell cultures into efficient digital mass cell cultures. This platform could be useful for industrial applications of cell cultures such as in vitro toxicity testing of drugs and cosmetics and clinical scale production of cells for cell therapy.

Analysis of Women's Health Online News Articles Using Topic Modeling.

OBJECTIVES: This research aimed to understand the popularity of topics in the field of women's health through analysis of online news articles which were chronologically classified and examined to determine how women's health and diseases had changed over time. METHODS: Women's health and disease news articles were collated from a popular news website between 1993 to 2015 and preprocessed using gynecological medical terminology, Korean words and nouns (excluding general nouns not related to women's healthcare topics). The resultant articles (N = 7,710) were analyzed using the Latent Dirichlet Allocation algorithm and major topics were extracted. Topic trends were analyzed by year and period for women's health. RESULTS: It was observed that most of the women's health articles were focused on "Healthcare", and 9 other topics were identified that represented a relatively small proportion in 1993-2000. In 2001-2005, most of the articles were focused on "Medical Services" and "Dietary Supplements" with some specific topics that peaked people's interest, as compared to those focused on "Healthcare" in the 1990s. It was also observed that differences in the proportion of each topic was small after 2011. CONCLUSION: Changes in topics related to women's disease were not clearly distinguished in the 1990s but this changed from 2001where articles related to "women disease" appeared as articles on the topics of various diseases.

Wearable and Implantable Soft Bioelectronics Using Two-Dimensional Materials.

Soft bioelectronics intended for application to wearable and implantable biomedical devices have attracted great attention from material scientists, device engineers, and clinicians because of their extremely soft mechanical properties that match with a variety of human organs and tissues, including the brain, heart, skin, eye, muscles, and neurons, as well as their wide diversity in device designs and biomedical functions that can be finely tuned for each specific case of applications. These unique features of the soft bioelectronics have allowed minimal mechanical and biological damage to organs and tissues integrated with bioelectronic devices and reduced side effects including inflammation, skin irritation, and immune responses even after long-term biointegration. These favorable properties for biointegration have enabled long-term monitoring of key biomedical indicators with high signal-to-noise ratio, reliable diagnosis of the patient's health status, and in situ feedback therapy with high treatment efficacy optimized for the requirements of each specific disease model. These advantageous device functions and performances could be maximized by adopting novel high-quality soft nanomaterials, particularly ultrathin two-dimensional (2D) materials, for soft bioelectronics. Two-dimensional materials are emerging material candidates for the channels and electrodes in electronic devices (semiconductors and conductors, respectively). They can also be applied to various biosensors and therapeutic actuators in soft bioelectronics. The ultrathin vertically layered nanostructure, whose layer number can be controlled in the synthesis step, and the horizontally continuous planar molecular structure, which can be found over a large area, have conferred unique mechanical, electrical, and optical properties upon the 2D materials. The atomically thin nanostructure allows mechanical softness and flexibility and high optical transparency of the device, while the large-area continuous thin film structure allows efficient carrier transport within the 2D plane. In addition, the quantum confinement effect in the atomically thin 2D layers introduces interesting optoelectronic properties and superb photodetecting capabilities. When fabricated as soft bioelectronic devices, these interesting and useful material features of the 2D materials enable unconventional device functions in biological and optical sensing, as well as superb performance in electrical and biochemical therapeutic actuations. In this Account, we first summarize the distinctive characteristics of the 2D materials in terms of the mechanical, optical, chemical, electrical, and biomedical aspects and then present application examples of the 2D materials to soft bioelectronic devices based on each aforementioned unique material properties. Among various kinds of 2D materials, we particularly focus on graphene and MoS2. The advantageous material features of graphene and MoS2 include ultrathin thickness, facile functionalization, large surface-to-volume ratio, biocompatibility, superior photoabsorption, and high transparency, which allow the development of high-performance multifunctional soft bioelectronics, such as a wearable glucose patch, a highly sensitive humidity sensor, an ultrathin tactile sensor, a soft neural probe, a soft retinal prosthesis, a smart endoscope, and a cell culture platform. A brief comparison of their characteristics and performances is also provided. Finally, this Account concludes with a future outlook on next-generation soft bioelectronics based on 2D materials.

Human eye-inspired soft optoelectronic device using high-density MoS2-graphene curved image sensor array.

Soft bioelectronic devices provide new opportunities for next-generation implantable devices owing to their soft mechanical nature that leads to minimal tissue damages and immune responses. However, a soft form of the implantable optoelectronic device for optical sensing and retinal stimulation has not been developed yet because of the bulkiness and rigidity of conventional imaging modules and their composing materials. Here, we describe a high-density and hemispherically curved image sensor array that leverages the atomically thin MoS2-graphene heterostructure and strain-releasing device designs. The hemispherically curved image sensor array exhibits infrared blindness and successfully acquires pixelated optical signals. We corroborate the validity of the proposed soft materials and ultrathin device designs through theoretical modeling and finite element analysis. Then, we propose the ultrathin hemispherically curved image sensor array as a promising imaging element in the soft retinal implant. The CurvIS array is applied as a human eye-inspired soft implantable optoelectronic device that can detect optical signals and apply programmed electrical stimulation to optic nerves with minimum mechanical side effects to the retina.

Application of Queueing Theory to the Analysis of Changes in Outpatients' Waiting Times in Hospitals Introducing EMR.

OBJECTIVES: This research used queueing theory to analyze changes in outpatients' waiting times before and after the introduction of Electronic Medical Record (EMR) systems. METHODS: We focused on the exact drawing of two fundamental parameters for queueing analysis, arrival rate (λ) and service rate (µ), from digital data to apply queueing theory to the analysis of outpatients' waiting times. We used outpatients' reception times and consultation finish times to calculate the arrival and service rates, respectively. RESULTS: Using queueing theory, we could calculate waiting time excluding distorted values from the digital data and distortion factors, such as arrival before the hospital open time, which occurs frequently in the initial stage of a queueing system. We analyzed changes in outpatients' waiting times before and after the introduction of EMR using the methodology proposed in this paper, and found that the outpatients' waiting time decreases after the introduction of EMR. More specifically, the outpatients' waiting times in the target public hospitals have decreased by rates in the range between 44% and 78%. CONCLUSIONS: It is possible to analyze waiting times while minimizing input errors and limitations influencing consultation procedures if we use digital data and apply the queueing theory. Our results verify that the introduction of EMR contributes to the improvement of patient services by decreasing outpatients' waiting time, or by increasing efficiency. It is also expected that our methodology or its expansion could contribute to the improvement of hospital service by assisting the identification and resolution of bottlenecks in the outpatient consultation process.

Effects of Anti-Smoking Public Service Announcements on the Attitudes of Korean College Students toward Smoking.

OBJECTIVES: This study aimed to identify the effects of anti-smoking public service announcements on the attitudes of Korean college students toward smoking. METHODS: This study involved students via convenience sampling from seven universities who were randomly assigned to four groups. All groups completed a preliminary questionnaire, before being shown a public service announcement twice, and then completed a post viewing questionnaire. RESULTS: For announcements with positive messages, the proportion of changes in beliefs and attitudes were 39.1% and 19.8%, respectively, whereas those with negative messages showed a greater proportion of changes in the beliefs (59.7%) and attitudes (40.3%). After adjusting for sex and change in belief, the message types and smoking status were identified as factors affecting the change in the participants attitudes. A negative message resulted in a greater change in attitudes (odds ratio [OR], 3.047; 95% confidence interval [CI], 1.847-5.053). Ever-smokers including current smokers showed a greater positive change in attitude than never-smokers (OR, 6.965; 95% CI, 4.107-11.812). CONCLUSION: This study found that positive anti-smoking public service announcements were more effective on attitude change than negative messages. Additionally these announcements were more effective among viewers who were current smokers or had a prior smoking experience.

Diffusion of Electronic Medical Record Based Public Hospital Information Systems.

OBJECTIVES: This study was conducted to evaluate the adoption behavior of a newly developed Electronic Medical Record (EMR)-based information system (IS) at three public hospitals in Korea with a focus on doctors and nurses. METHODS: User satisfaction scores from four performance layers were analyzed before and two times after the newly develop system was introduced to evaluate the adoption process of the IS with Rogers' diffusion theory. RESULTS: The 'intention to use' scores, the most important indicator for determining whether or not to adopt the IS in Rogers' confirmation stage for doctors, were very high in the third survey (4.21). In addition, the scores for 'reduced medication errors', which is the key indicator for evaluating the success of the IS, increased in the third survey for both doctors and nurses. The factors influencing 'intention to use' with a high odds ratio (>1.5) were the 'frequency of attendance of user training sessions', 'mandatory use of system', 'reduced medication errors', and 'reduced medical record documentation time' for both doctors and nurses. CONCLUSIONS: These findings show that the new EMR-based IS was well accepted by doctors. Both doctors and nurses also positively considered the effects of the new IS on their clinical environments.

A contrasting function for miR-137 in embryonic mammogenesis and adult breast carcinogenesis.

MicroRNAs are differentially expressed in breast cancer cells and have been implicated in cancer formation, tumour invasion and metastasis. We investigated the miRNA expression profiles in the developing mammary gland. MiR-137 was expressed prominently in the developing mammary gland. When the miR-137 was over-expressed in the embryo, the mammary epithelium became thickened. Moreover, genes associated with mammary gland formation such as Tbx3 and Lef1 were not expressed. This suggests that miR-137 induces gland formation and invasion. When miR-137 was over-expressed in MDA-MB-231 cells, their ability to form tumours in adult mice was significantly reduced. These data support miR-137 decides epithelial cell behavior in the human breast cancer. It also suggests that miR-137 is a potential therapeutic target for amelioration of breast cancer progression.

Multifunctional cell-culture platform for aligned cell sheet monitoring, transfer printing, and therapy.

While several functional platforms for cell culturing have been proposed for cell sheet engineering, a soft integrated system enabling in vitro physiological monitoring of aligned cells prior to their in vivo applications in tissue regeneration has not been reported. Here, we present a multifunctional, soft cell-culture platform equipped with ultrathin stretchable nanomembrane sensors and graphene-nanoribbon cell aligners, whose system modulus is matched with target tissues. This multifunctional platform is capable of aligning plated cells and in situ monitoring of cellular physiological characteristics during proliferation and differentiation. In addition, it is successfully applied as an in vitro muscle-on-a-chip testing platform. Finally, a simple but high-yield transfer printing mechanism is proposed to deliver cell sheets for scaffold-free, localized cell therapy in vivo. The muscle-mimicking stiffness of the platform allows the high-yield transfer printing of multiple cell sheets and results in successful therapies in diseased animal models. Expansion of current results to stem cells will provide unique opportunities for emerging classes of tissue engineering and cell therapy technologies.