Wearable Pressure/Touch Sensors Based on Hybrid Dielectric Composites of Zinc Oxide Nanowires/Poly(dimethylsiloxane) and Flexible Electrodes of Immobilized Carbon Nanotube Random Networks

Capacitive-type physical sensors based on hybrid dielectric composites of zinc oxide nanowires/poly­(dimethylsiloxane) (ZnO NWs@PDMS) and flexible electrodes of immobilized carbon nanotube (CNT) random networks, which are highly sensitive to pressure and touch stimuli, are demonstrated. Immobilized CNT random networks densely entangled in a Nafion matrix improve the electrical stability of wearable pressure sensors against mechanical stress with a bending radius of 5 mm. The effect of ZnO NW incorporation into PDMS on the sensing performance of pressure sensors is investigated, which results in a significantly enhanced sensitivity of 8.77 × 10–4 Pa–1 in low-pressure regions, compared to pristine PDMS (1.32 × 10–4 Pa–1). This improvement is attributed to the increase in the effective dielectric constant (εr) of the hybrid dielectric composites with their piezoelectric properties. In addition, wearable pressure/touch sensor arrays capable of detecting ultralow pressures (down to 20 Pa) and the real-time identification of touch and pressure stimuli via different sensing mechanisms are demonstrated. We believe that the multifunctionality introduced by the proposed sensors can extend the potential of physical sensor applications, while they are suitable for integration with wearable electronics based on hybrid nanocomposites and interfaces

Spontaneously sp²‑Carbonized Fluorescent Polyamides as a Probe Material for Bioimaging

Spontaneously sp2-carbonized polyamides (PA1, PA2) were prepared via Knoevenagel-type side reactions of malonyl moieties under mild conditions in the polycondensation of dicarbonyl chloride and diamine. Both polymers were soluble in water and emissive in the visible region, and the fluorescence (FL) intensity and the maximum wavelength were highly dependent on the excitation wavelength and the pH. Their chemical structures and FL origin were clarified by performing various spectroscopic analyses. π*−π transition was assumed to be allowed in an enol form based on the conjugated structure formed by the side reaction; this was responsible for its pH dependency and high FL quantum efficiency. In particular, PA2, which comprises the tertiary amide linkage, showed quick endocytosis, low cytotoxicity, excellent biocompatibility, and exclusively stained lysosomes with the lowest intracellular pH. These results will help in understanding the origin of the FL emission of carbonized nanomaterials and exploring more advanced functions in the field of bioimaging

Quinoline Compound KM11073 Enhances BMP-2-Dependent Osteogenic Differentiation of C2C12 Cells via Activation of p38 Signaling and Exhibits <i>In Vivo</i> Bone Forming Activity

<div><p>Recombinant human bone morphogenetic protein (rhBMP)-2 has been approved by the FDA for clinical application, but its use is limited due to high cost and a supra-physiological dose for therapeutic efficacy. Therefore, recent studies have focused on the generation of new therapeutic small molecules to induce bone formation or potentiate the osteogenic activity of BMP-2. Here, we show that [4-(7-chloroquinolin-4-yl) piperazino][1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]methanone (KM11073) strongly enhances the BMP-2-stimulated induction of alkaline phosphatase (ALP), an early phase biomarker of osteoblast differentiation, in bi-potential mesenchymal progenitor C2C12 cells. The KM11073-mediated ALP induction was inhibited by the BMP antagonist noggin, suggesting that its osteogenic activity occurs via BMP signaling. In addition, a pharmacological inhibition study suggested the involvement of p38 activation in the osteogenic action of KM11073 accompanied by enhanced expression of BMP-2, -6, and -7 mRNA. Furthermore, the <i>in vivo</i> osteogenic activity of KM11073 was confirmed in zebrafish and mouse calvarial bone formation models, suggesting the possibility of its single use for bone formation. In conclusion, the combination of rhBMP-2 with osteogenic small molecules could reduce the use of expensive rhBMP-2, mitigating the undesirable side effects of its supra-physiological dose for therapeutic efficacy. Moreover, due to their inherent physical properties, small molecules could represent the next generation of regenerative medicine.</p></div

Effect of KM11073 on the activation of p38.

<p>Cells (1 × 10⁵ cells/well) were cultured in a 6-well plate for 1 day and then incubated with DMEM containing 5% FBS in the presence or absence of BMP-2 and/or KM11073 (<i>A</i>). Inhibitory effects of p38 inhibitors (1, SB202190; 2, PD169316; 3, SB203580) on the activation of p38 by BMP-2 and KM11073. Western blot analysis was performed with protein samples prepared with cells treated with each inhibitor for 30 min and then incubated with BMP-2 and KM11073 for 30 min (<i>B</i>). The relative, normalized ratio between phosphorylated protein and the protein itself was presented.</p

Osteogenesis-related gene expression in zebrafish.

<p>At 5.0 dpf, larvae were treated with KM11073 (1 μM), and after 1 day the mRNA levels were evaluated by quantitative real-time PCR. Fold changes relative to each gene level in the control are presented as mean ± standard deviation.</p><p>* <i>p</i> < 0.05</p><p>** <i>p</i> < 0.01 (compared to the control).</p><p>Osteogenesis-related gene expression in zebrafish.</p

KM11073 enhanced BMP-2-induced osteoblast differentiation in C2C12 cells.

<p>Cell viability was assayed 1 and 3 days after treatment with KM11073 (<i>A</i>). Effect of KM11073 on BMP-2-stimulated ALP induction. Cells (4 × 10³ cells/well) were cultured in a 96-well plate for 1 day and then the medium replaced with DMEM containing 5% FBS and KM11073 in the presence or absence of rhBMP-2 (100 ng/ml). The medium was changed every 3 days. On differentiation day 6, ALP staining and its activity were assayed <i>(B)</i>. Effect of noggin on KM11073-mediated enhancement of BMP-2-stimulated ALP induction. Osteogenesis was enhanced by KM11073 in the presence of BMP-2 on differentiation days 0 and 2, and then noggin was treated on differentiation day 4. On differentiation day 6, ALP staining and its activity were assayed (<i>C</i>). *** <i>p</i> < 0.001 compared to the BMP-2-treated group; ^##<i>p</i> < 0.01, ^###<i>p</i> < 0.001 compared to the group treated with BMP-2 and KM11073.</p

Involvement of p38 inhibitors in the KM11073-mediated enhancement of BMP-2-stimulated induction of osteogenic genes.

<p>Cells were treated with each inhibitor for 2 h and then incubated with BMP-2 (100 ng/ml) and KM11073 (10 μM) for 3 days. The mRNA expression levels were evaluated by quantitative real-time PCR. Fold changes relative to each gene level in the control are presented as mean ± standard deviation</p><p>* <i>p</i> < 0.05</p><p>** <i>p</i> < 0.01 (compared to the control)</p><p>^#<i>p</i> < 0.05</p><p>^##<i>p</i> < 0.01 (compared to the group treated with BMP-2)</p><p>^†<i>p</i> < 0.05</p><p>^††<i>p</i> < 0.01 (compared to the group treated with BMP-2 + KM11073).</p><p>Involvement of p38 inhibitors in the KM11073-mediated enhancement of BMP-2-stimulated induction of osteogenic genes.</p

Involvement of p38 in the KM11073-mediated enhancement of BMP-2-stimulated ALP induction.

<p>In a 96-well plate, cells (4 × 10³ cells/well) were treated with each inhibitor for 2 h and then treated with BMP-2 and KM11073. After 3 days, the cells were treated with each inhibitor. On differentiation day 6, ALP staining (A) and its activity (B) were assayed. ^###<i>p</i> < 0.001 compared to the BMP-2-treated group; * <i>p</i> < 0.05, ** <i>p</i> < 0.01, *** <i>p</i> < 0.001 compared to the group treated with BMP-2 and KM11073.</p

Evaluation of the <i>in vivo</i> osteogenic activity of KM11073 in zebrafish and mouse calvariae.

<p>Five days after fertilization, zebrafish were treated with KM11073 (1 μM) for 2 days and then fixed and stained with alizarin red S. The parasphenoid (ps), notochord (n), ceratobranchial 5 (cb5), otolith (ot), and vertebrae (vb) are indicated with arrows (<i>A</i>). Collagen sponges soaked in 5 μl of 2.5 or 5 mM KM11073 were placed onto mouse calvarial bones. After 3-week implantation, the mice were sacrificed. Calvarial bones were removed, fixed, decalcified, embedded in paraffin, and sectioned. Sections were stained with H&E and photographed at 200 × magnification. Arrows indicate the thickness of newly formed woven bones (<i>B</i>). The thickness of newly formed woven bones was quantified compared to the scale bar.</p

Chemical structure of KM11073.

<p>Chemical structure of KM11073.</p