Outer retinal degeneration in a non-human primate model using temporary intravitreal tamponade with N-methyl-N-nitrosourea in cynomolgus monkeys.

Objective:The main objective of this study was to induce and evaluate drug-dose-dependent outer retinal degeneration in cynomolgus monkeys by application of N-methyl-N-nitrosourea (MNU).Approach:Intravitreal temporary tamponade induced outer retinal degeneration with MNU solutions (2-3 mg ml-1) after vitrectomy in five cynomolgus monkeys. Optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ffERG), and visual evoked potentials (VEP) were performed at baseline and weeks 2, 6, and 12 postoperatively. At week 12, OCT angiography, histology, and immunohistochemistry were performed.Main results:Outer retinal degeneration was observed in four monkeys, especially in the peripheral retina. Anatomical and functional changes occurred at week 2 and persisted until week 12. FAF images showed hypoautofluorescence dots, similar to AF patterns seen in human retinitis pigmentosa. Hyperautofluorescent lesions in the pericentral area were also observed, which corresponded to the loss of the ellipsoid zone on OCT images. OCT revealed thinning of the outer retinal layer adding to the loss of the ellipsoid zone outside the vascular arcade. Histological findings confirmed that the abovementioned changes resulted from a gradual loss of photoreceptors from the perifovea to the peripheral retina. In contrast, the inner retina, including ganglion cell layers, was preserved. Functionally, a decrease or extinction of scotopic ffERGs was observed, which indicated rod-dominant loss. Nevertheless, VEPs were relatively preserved.Significance:Therefore, we can conclude that temporary exposure to intravitreal MNU tamponade after vitrectomy induces rod-dominant outer retinal degeneration in cynomolgus monkeys, especially in the peripheral retina.

Analysis of Microvasculature in Nonhuman Primate Macula With Acute Elevated Intraocular Pressure Using Optical Coherence Tomography Angiography.

Purpose: To investigate responses of macular capillary vessel area density (VAD) of superficial and deep retinal vascular plexuses to elevations in intraocular pressure (IOP) in cynomolgus macaque monkeys using optical coherence tomography angiography (OCTA). Methods: In five general anesthetized male cynomolgus monkeys, the IOP was increased incrementally by 10 mmHg from baseline (10 mmHg) to 70 mmHg and then decreased back to 10 mmHg (recovery state). Structural OCT (30° × 30°) and OCTA (20° × 15°) centered on the macula were obtained at each IOP and 3, 15, and 30 minutes after recovery. En face images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were extracted, and VAD (%) compared with that at baseline was calculated. Results: The VADs in the SVC and DVC at baseline and at 30 mmHg IOP were 34.96%, 34.15%, 35.38%, and 30.12%, respectively. The VAD plateaued until 30 mmHg; however, the VAD was affected more in the DVC than in the SVC (P = 0.008) at 30 mmHg. It showed a significant reduction at 40 mmHg (16.52% SVC, P = 0.006; 18.59% DVC, P = 0.012). In the recovery state, the SVC showed full retention of baseline VAD, but the DVC maintained VAD approximately 70% of that at baseline. Structural OCT showed hyperreflectivity in the nuclear layer, retinal swelling, and an undifferentiated ellipsoid zone from 50 mmHg. Conclusions: Despite physiological autoregulation, perifoveal microcirculation was affected at high IOP ≥ 40 mmHg, especially in the DVC, which explains the pathological mechanism of macular vulnerability in ischemic diseases.

Normative Data of Ocular Biometry, Optical Coherence Tomography, and Electrophysiology Conducted for Cynomolgus Macaque Monkeys.

Purpose: To present normative data of optical coherence tomography (OCT) parameters, electrophysiological tests, and optical biometry conducted for cynomolgus monkeys. Methods: Multimodal examinations were performed for 11 adult cynomolgus monkeys (Macaca fascicularis, weighing 2.6-7.5 kg, aged 45-99 months). A-scan biometry was performed to measure ocular biometry. OCT images were obtained at 30° and 55°. After the pupils were fully dilated, electroretinogram (ERG) and visual evoked potentials (VEP) were recorded with a commercial system using a contact lens electrode. Results: All cynomolgus monkeys were males. The mean axial length was 17.92 ± 0.34 mm. The central total retinal layer (TRL) and subfoveal choroidal thicknesses were 286.27 ± 18.43 and 234.73 ± 53.93 µm, respectively. The TRL and nerve fiber layer thickness was greater in the nasal than in other quadrants in the Early Treatment Diabetic Retinopathy Study circle in the macula. Peripheral TRL and ganglion cell complex thickness on the temporal outside the vascular arcades were lower than on the other sides. The peak latency of a-wave and b-wave in scotopic and photopic 3.0 ERG was 14.78 ± 1.00 and 32.89 ± 1.81 ms, and 12.91 ± 1.03 and 31.79 ± 2.16 ms, respectively. The n2 wave peak latency of VEP was 15.21 ± 8.07 ms. The a-wave peak latency of ERG and the n2 wave peak latency of VEP negatively correlated with age. Conclusions: The normative ocular biometric, electrophysiological test, and OCT parametric data of cynomolgus monkeys could serve as reference values for further preclinical studies. Translational Relevance: We present normative data of cynomolgus monkeys' eyes, an adequate animal model for preclinical studies.

Effect of Viscosity on the Formation of Porous Polydimethylsiloxane for Wearable Device Applications.

Medical devices, which enhance the quality of life, have experienced a gradual increase in demand. Various research groups have attempted to incorporate soft materials such as skin into wearable devices. We developed a stretchable substrate with high elasticity by forming a porous structure on polydimethylsiloxane (PDMS). To optimize the porous structure, we propose a manufacturing process that utilizes a high-pressure steam with different viscosities (400, 800, 2100, and 3000 cP) of an uncured PDMS solution. The proposed method simplifies the manufacturing of porous structures and is cost-effective compared to other technologies. Porous structures of various viscosities were formed, and their electrical and mechanical properties evaluated. Porous PDMS (3000 cP) was formed in a sponge-like three-dimensional porous structure, compared to PDMS formed by other viscosities. The elongation of porous PDMS (3000 cP) was increased by up to 30%, and the relative resistance changed to less than 1000 times with the maximum strain test. The relative resistance increased the initial resistance (R0) by approximately 10 times during the 1500-times repeated cycling tests with 30% strain. As a result, patch-type wearable devices based on soft materials can provide an innovative platform that can connect with the human skin for robotics applications and for continuous health monitoring.

Highly Stretchable Dry Electrode Composited with Carbon Nanofiber (CNF) for Wearable Device.

In this work, we present a highly stretchable dry electrode composited with carbon nanofiber (CNF) for wearable device by simple method. The fabricated electrodes were assembled with snap connector for connect with electric circuit and sticky polymer for improving adhesion strength on the skin. We evaluated the electrical and mechanical properties depending on the weight % (wt%) and thickness of CNF/elastomer composited stretchable electrode. From the results, the electrical characteristic was improved as increasing concentrations of CNF and their dropping volume. And we evaluated a stretchability and electromechanical property using with cycling test. Through these tests, we have demonstrated that fabricated dry electrode has outstanding stretchability and durability under stretching condition. Finally, electrocardiogram (ECG) was measured with these electrodes. The results of ECG measurement showed similar or larger signal that of commercial wet electrode. Consequently, these results are expected to apply as a wearable device such as a bio-signal measurement and strain sensors.

Serpentine-pattern effects on the biaxial stretching of percolative graphene nanoflake films.

Stretchable strain sensors based on percolative arrangements of conducting nanoparticles are essential tools in stretchable electronics and have achieved outstanding performance. Introducing serpentine patterns for strain-sensing materials is a very effective method for enhancing stretchability with a quantified structural resistance through a simple, reliable, and facile approach. Here, we investigate serpentine-pattern effects in the electrical responses to biaxial stretching for percolative graphene-nanoparticle films. Graphene nanoplatelet films are applied to a stretchable substrate using a facile spray-coating technique, for a variety of serpentine pattern shapes, aspect ratios, pattern frequencies, and number of coatings. The electrical responses after applying biaxial stretching (x-axis and y-axis) are measured and analyzed for comparison. The serpentine patterns that would be suitable for stretchable electrodes, sensitive sensors, and highly stretchable sensors are then identified. This work demonstrates the advantage of using serpentine patterns for stretchable strain sensors and offers guidelines for selecting suitable pattern types for strain sensors in stretchable-electronics applications.

Water-Resistant and Skin-Adhesive Wearable Electronics Using Graphene Fabric Sensor with Octopus-Inspired Microsuckers.

Wearable and skin-attachable electronics with portable/wearable and stretchable smart sensors are essential for health-care monitoring devices or systems. The property of adhesion to the skin in both dry and wet environments is strongly required for efficient monitoring of various human activities. We report here a facile, low-cost, scalable fabrication method for skin-adhesive graphene-coated fabric (GCF) sensors that are sensitive and respond fast to applied pressure and strain. With octopus-like patterns formed on the side of the GCF that touches the skin, the GCF adheres strongly to the skin in both dry and wet environments. Using these characteristics, we demonstrate efficient monitoring of a full range of human activities, including human physiological signals such as wrist pulse and electrocardiography (ECG), as well as body motions and speech vibrations. In particular, both measurements of ECG and wrist-bending motions were demonstrated even in wet conditions. Our approach has opened up a new possibility for wearable and skin-adherent electronic fabric sensors working even in wet environments for health-care monitoring and medical applications in vitro and in vivo.

Highly twisted supercoils for superelastic multi-functional fibres.

Highly deformable and electrically conductive fibres with multiple functionalities may be useful for diverse applications. Here we report on a supercoil structure (i.e. coiling of a coil) of fibres fabricated by inserting a giant twist into spandex-core fibres wrapped in a carbon nanotube sheath. The resulting supercoiled fibres show a highly ordered and compact structure along the fibre direction, which can sustain up to 1,500% elastic deformation. The supercoiled fibre exhibits an increase in resistance of 4.2% for stretching of 1,000% when overcoated by a passivation layer. Moreover, by incorporating pseudocapacitive-active materials, we demonstrate the existence of superelastic supercapacitors with high linear and areal capacitance values of 21.7 mF cm-1 and 92.1 mF cm-2, respectively, that can be reversibly stretched by 1,000% without significant capacitance loss. The supercoiled fibre can also function as an electrothermal artificial muscle, contracting 4.2% (percentage of loaded fibre length) when 0.45 V mm-1 is applied.

CNT/PDMS composite flexible dry electrodes for long-term ECG monitoring.

We fabricated a carbon nanotube (CNT)/ polydimethylsiloxane (PDMS) composite-based dry ECG electrode that can be readily connected to conventional ECG devices, and showed its long-term wearable monitoring capability and robustness to motion and sweat. While the dispersion of CNTs in PDMS is challenging, we optimized the process to disperse untreated CNTs within PDMS by mechanical force only. The electrical and mechanical characteristics of the CNT/PDMS electrode were tested according to the concentration of CNTs and its thickness. The performances of ECG electrodes were evaluated by using 36 types of electrodes which were fabricated with different concentrations of CNTs, and with a differing diameter and thickness. The ECG signals were obtained by using electrodes of diverse sizes to observe the effects of motion and sweat, and the proposed electrode was shown to be robust to both factors. The CNT concentration and diameter of the electrodes were critical parameters in obtaining high-quality ECG signals. The electrode was shown to be biocompatible from the cytotoxicity test. A seven-day continuous wearability test showed that the quality of the ECG signal did not degrade over time, and skin reactions such as itching or erythema were not observed. This electrode could be used for the long-term measurement of other electrical biosignals for ubiquitous health monitoring including EMG, EEG, and ERG.

A method for stable electrical connection of a multi-channeled polyimide electrode with PCB.

We propose a novel packaging method of a thin polyimide multichannel microelectrode. For the simple electrical connection of polyimide (PI) electrodes, we made a via-hole at the interconnection pads of thin PI electrodes, and constructed a Ni ring by electroplating through the via-hole for the stable soldering and strong adhesion of the electrode to PCB. For the construction of a well-organized Ni ring, the electroplating condition was optimized, and the electrical property of the packaged electrode was evaluated. A 40 channel thin PI electrode was fabricated and packaged by the proposed method, and we performed the animal experiment with this packaged electrode for the high-resolution recording of neural signals from the skull of a rat.