Manufacturing Process of Polymeric Microneedle Sensors for Mass Production.

In this work, we present a fabrication process for microneedle sensors made of polylactic acid (PLA), which can be utilized for the electrochemical detection of various biomarkers in interstitial fluid. Microneedles were fabricated by the thermal compression molding of PLA into a laser machined polytetrafluoroethylene (PTFE) mold. Sensor fabrication was completed by forming working, counter, and reference electrodes on each sensor surface by Au sputtering through a stencil mask, followed by laser dicing to separate individual sensors from the substrate. The devised series of processes was designed to be suitable for mass production, where multiple microneedle sensors can be produced at once on a 4-inch wafer. The operational stability of the fabricated sensors was confirmed by linear sweep voltammetry and cyclic voltammetry at the range of working potentials of various biochemical molecules in interstitial fluid.

Paper-Based Ionic Thermocouples for Inexpensive and High-Precision Measurement of Temperature.

Accurate and yet cost-effective temperature measurements are required in various sectors of academia and industry. Thermocouples (TCs) are most widely used for temperature measurements; however, their low temperature sensitivity and high thermal conductivity should be improved to ensure the reliable measurement of output voltage for small temperature differences. To address this, a paper-based ionic thermocouple (P-iTC) presented here utilizes a pair of paper strips soaked with the electrolytes of potassium ferri-/ferrocyanide and iron (II/III) chloride redox couples, which are used as p- and n-type elements, respectively. The fabricated P-iTC provides 70× higher temperature sensitivity (α, 2.8 mV/K) and 30× lower thermal conductivity (k, 0.8 W/m K) than those of commercial K-type TCs, thereby yielding a remarkably high α/k ratio of 3.5 mV m/W. Reliable sensing performance is measured during three weeks of operation, which indicates that the P-iTC should be stable in long-term operation. To demonstrate the practicality of the P-iTC, a 3 × 3 planar array of P-iTCs is fabricated to monitor the temperature profile of a surface in contact with heat sources. Using pencil-drawn graphite electrodes on paper, a highly cost-effective P-iTC with the material cost of ∼0.5 cents per device is also fabricated, which is successfully used to monitor cold chain temperatures while retaining its excellent temperature-sensing performance.

Thermocells for Hybrid Photovoltaic/Thermal Systems.

The photovoltaic conversion efficiency of solar cells is highly temperature dependent and decreases with increasing temperature. Therefore, the thermal management of solar cells is crucial for the efficient utilization of solar energy. We fabricate a hybrid photovoltaic/thermocell (PV/T) module by integrating a thermocell directly into the back of a solar panel and explore the feasibility of the module for its practical implementation. The proposed PV/T hybrid not only performs the cooling of the solar cells but also produces an additional power output by converting the heat stored in the solar cell into useful electric energy through the thermocell. Under illumination with an air mass of 1.5 G, the conversion efficiency of the solar cell can improve from 13.2% to 15% by cooling the solar cell from 61 °C to 34 °C and simultaneously obtaining an additional power of 3.53 µW/cm2 from the thermocell. The advantages of the PV/T module presented in this work, such as the additional power generation from the thermocell as well as the simultaneous cooling of the solar cells and its convenient installation, can lead to the module's importance in practical and large-scale deployment.

A cell-free extract from human adipose stem cells protects mice against epilepsy.

PURPOSE: Stem cell-based therapies are being considered for various neurologic diseases, such as epilepsy. Recent studies have suggested that some effects of transplanted stem cells are due to bystander effects that modulate the host environment, rather than direct effects of cell replacement. The extract from human adipose stem cells (ASCs) that secrete multiple growth factors including cytokines and chemokines may be a potential source of bystander effects for the treatment of epilepsy, in which inflammation is thought to play an important role. Here, we investigated the effects of a cytosolic extract of human ASCs (ASCs-E) in a mouse model of epilepsy. METHODS: Human ASCs-E, boiled ASCs-E, or fibroblast-extract (fibroblast-E) was intraperitoneally administrated to C57BL/6 mice 15 min before pilocarpine-induced status epilepticus (SE) or during chronic epileptic stage. Blood-brain barrier (BBB) leakage was evaluated by measuring Evans blue dye extravasation. Spontaneous recurrent seizure (SRS) was investigated by long-term video-electroencephalography (EEG) monitoring. The mice performed elevated plus maze, open-field, light/dark transition, and novel object recognition tasks. KEY FINDINGS: Acute application of human ASCs-E before SE led to earlier attenuation of seizure spike activities after treatment with diazepam, reduction of BBB leakage, and inhibition of the development of epilepsy. Human ASCs-E treatment (for 7 days) during the chronic epileptic stage suppressed SRS and reduced abnormal epileptic behavioral phenotypes. However, neither boiled ASCs-E nor fibroblast-E had any effects in the experimental epilepsy model. SIGNIFICANCE: Our results demonstrate that human ASCs-E prevents or inhibits epileptogenesis and SRS in mice. They also suggest a stem cell-based, noninvasive therapy for the treatment of epilepsy.

Cholinergic anti-inflammatory pathway in intracerebral hemorrhage.

Stimulated vagus nerve excretes acetylcholine into the peripheral immune organs such as the spleen, reducing innate inflammation. Here, we investigated whether activation of this "cholinergic anti-inflammatory pathway" can be used to reduce cerebral inflammation in a model of hemorrhagic stroke. Experimental intracerebral hemorrhage (ICH) was induced by stereotaxic collagenase injection in rats. Muscarine, an activator of the vagus nerve, or phosphate-buffered saline (control) was injected into the lateral ventricle after induction of ICH. Intraventricular muscarine injection increased heart rate variability in the ICH model, suggesting increased vagus nerve output. Muscarine-injected ICH rats showed improved neurologic outcomes, reduced brain water content, and decreased levels of inflammatory mediators in both brain and spleen. Central muscarine injection was ineffective at reducing cerebral edema without spleen, suggesting that the effect of muscarine is mediated through the vagus nerve-spleen pathway rather than through a direct interaction with the brain. Our results suggest that the brain possesses a cholinergic anti-inflammatory pathway that counteracts the inflammatory responses after ICH, thereby limiting damage to the brain itself.

Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke.

Neural stem cell (NSC) transplantation has been investigated as a means to reconstitute the damaged brain after stroke. In this study, however, we investigated the effect on acute cerebral and peripheral inflammation after intracerebral haemorrhage (ICH). NSCs (H1 clone) from fetal human brain were injected intravenously (NSCs-iv, 5 million cells) or intracerebrally (NSCs-ic, 1 million cells) at 2 or 24 h after collagenase-induced ICH in a rat model. Only NSCs-iv-2 h resulted in fewer initial neurologic deteriorations and reduced brain oedema formation, inflammatory infiltrations (OX-42, myeloperoxidase) and apoptosis (activated caspase-3, TUNEL) compared to the vehicle-injected control animals. Rat neurosphere-iv-2 h, but not human fibroblast-iv-2 h, also reduced the brain oedema and the initial neurologic deficits. Human NSCs-iv-2 h also attenuated both cerebral and splenic activations of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-kappaB). However, we observed only a few stem cells in brain sections of the NSCs-iv-2 h group; in the main, they were detected in marginal zone of spleens. To investigate whether NSCs interact with spleen to reduce cerebral inflammation, we performed a splenectomy prior to ICH induction, which eliminated the effect of NSCs-iv-2 h transplantation on brain water content and inflammatory infiltrations. NSCs also inhibited in vitro macrophage activations after lipopolysaccharide stimulation in a cell-to-cell contact dependent manner. In summary, early intravenous NSC injection displayed anti-inflammatory functionality that promoted neuroprotection, mainly by interrupting splenic inflammatory responses after ICH.

Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhagic stroke model.

Adipose-derived stem cells (ASCs) are readily accessible multipotent mesenchymal stem cells and are known to secrete multiple growth factors, and thereby to have cytoprotective effects in various injury models. In the present study, the authors investigated the neuroprotective effect of ASCs in an intracerebral hemorrhage (ICH) model. ICH was induced via the stereotaxic infusion of collagenase, and human ASCs (three million cells per animal) isolated from human fresh fat tissue, were intravenously administered at 24 h post-ICH induction. Acute brain inflammation markers, namely, cell numbers positively stained for terminal transferase dUTP nick end labeling (TUNEL), myeloperoxidase (MPO), or OX-42, and brain water content were checked at 3 days post-ICH. In addition, the authors quantified brain degeneration by measuring hemispheric atrophy and perihematomal glial thickness at 6 weeks post-ICH, and determined modified limb placing behavioral scores weekly over 5 weeks post-ICH. The results showed that brain water content, TUNEL+, and MPO+ cell numbers were significantly reduced in the ASC-transplanted rats. ASC transplantation attenuated neurological deficits from 4 to 5 weeks post-ICH, and reduced both the brain atrophy and the glial proliferation at 6 weeks. Transplanted ASCs were found to densely populate perihematomal areas at 6 weeks, and to express endothelial markers (von Willebrand factor and endothelial barrier antigen), but not neuronal or glial markers. In summary, ASCs transplantation in the ICH model reduced both acute cerebral inflammation and chronic brain degeneration, and promoted long-term functional recovery.

Pharmacological induction of heat shock protein exerts neuroprotective effects in experimental intracerebral hemorrhage.

Heat shock proteins (HSPs) are reported to reduce inflammation and apoptosis in a variety of brain insults. Geranylgeranylacetone (GGA), developed as an antiulcer in Japan, has been known to induce HSP70 and to exert cytoprotective effects. In this study, we investigated whether GGA, as a specific HSP inducer, exerts therapeutic effects in experimentally induced intracerebral hemorrhage (ICH). ICH was induced with male Sprague-Dawley rats via the collagenase infusion. GGA (800 mg/kg) was administered via oral tube according to various schedules of treatment. The treatment with GGA, beginning before the induction of ICH and continuing until day 3, showed the reduction of brain water content and the increased level of HSP70 protein, as compared to the treatment with vehicle, although GGA started after the induction of ICH or administered as a single dose before ICH failed to up-regulate HSP70 and to reduce brain edema. The rats treated with GGA exhibited better functional recovery than those treated with vehicle. In the pre- and post- treatment group, inflammatory cells and cell death in the perihematomal regions were found to have been decreased. The treatment of GGA inhibited the mRNA expression of MMP-9, uPA, IL-6 and MIP-1, with concomitant increment of eNOS and phosphorylated STAT3 and Akt after ICH. We demonstrated that GGA induced a reduction in the brain edema along with marked inhibitory effects on inflammation and cell death after ICH.