Perfusable micro-vascularized 3D tissue array for high-throughput vascular phenotypic screening

Microfluidic organ-on-a-chip technologies have enabled construction of biomimetic physiologically and pathologically relevant models. This paper describes an injection molded microfluidic platform that utilizes a novel sequential edge-guided patterning method based on spontaneous capillary flow to realize three-dimensional co-culture models and form an array of micro-vascularized tissues (28 per 1 × 2-inch slide format). The MicroVascular Injection-Molded Plastic Array 3D Culture (MV-IMPACT) platform is fabricated by injection molding, resulting in devices that are reliable and easy to use. By patterning hydrogels containing human umbilical endothelial cells and fibroblasts in close proximity and allowing them to form vasculogenic networks, an array of perfusable vascularized micro-tissues can be formed in a highly efficient manner. The high-throughput generation of angiogenic sprouts was quantified and their uniformity was characterized. Due to its compact design (half the size of a 96-well microtiter plate), it requires small amount of reagents and cells per device. In addition, the device design is compatible with a high content imaging machine such as Yokogawa CQ-1. Furthermore, we demonstrated the potential of our platform for high-throughput phenotypic screening by testing the effect of DAPT, a chemical known to affect angiogenesis. The MV-IMPACT represent a significant improvement over our previous PDMS-based devices in terms of molding 3D co-culture conditions at much higher throughput with added reliability and robustness in obtaining vascular micro-tissues and will provide a platform for developing applications in drug screening and development.This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIT) (No. 2021R1A3B1077481). This study was also supported by a grant of the Korean Health Technol‑ ogy R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. HP20C0146010020), and by National Institutes of Health (R01HL141857 to YKH)

Desensitizing toothpastes for dentin sealing and tertiary dentin formation in vitro and in vivo: a comparative analysis

Background Dentin hypersensitivity is a painful response to external stimuli applied to exposed dentinal tubules. Various toothpastes with active desensitizing ingredients for the relief of dentin hypersensitivity are commercially available. However, data from several studies suggest that the effects of desensitizing toothpastes are unstable and brief. This study aimed to investigate the effect of toothpastes containing CPNE7-derived oligopeptide (CPNE7-DP) and other active desensitizing ingredients in the dentin microleakage, tubule occlusion and tertiary dentin formation. Methods Using scanning electron microscopy (SEM), we evaluated the patency of dentinal tubules on the surface of human dentin disks after brushing experiments with the various toothpastes. Dentin was histologically evaluated in a hypersensitivity model of canine teeth, after the exposed dentin area was brushed for 6 weeks. The toothpaste used in group 1 (control) did not contain any desensitizing ingredients; that used in group 2 contained CPNE7-DP; Colgate Sensitive was used in group 3; and Sensodyne Rapid Relief was used in group 4. Finally, we conducted microleakage analysis to investigate the dentin sealing effect. The microleakage analysis data were subjected to one-way ANOVA and post-hoc Tukey tests (alpha = 0.05). Results In the SEM images, all four groups of teeth exhibited partial occlusion of the dentinal tubules on the tooth surface. In the in vivo hypersensitivity model, group 2 exhibited a newly formed tertiary dentin, whereas no new hard tissue formation was observed in groups 1, 3, and 4. Microleakage analysis revealed that the volume of dentinal fluid flow was significantly smaller in group 2 than in group 1. Conclusions These results indicate that CPNE7-DP is a promising active ingredient with long-term dentin sealing effects.This study was supported by the Basic Science Research Program implemented by the Ministry of Science and ICT of South Korea and the National Research Foundation (Grant No. NRF‑ 2018R1A5A2024418) and a Korea Medical Device Development Fund grant (Project Number: 9991007198, KMDF_PR_20200901_0068‑2021‑02) funded by the Korean government (the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health & Welfare; and the Ministry of Food and Drug Safety)

Presenilin 2 N141I mutation induces hyperactive immune response through the epigenetic repression of REV-ERB alpha

Hyperimmunity is associated with Alzheimer disease. Here the authors show that the Presenilin 2 N141I mutation causes overproduction of clock-controlled cytokines and memory deficits through suppression of REV-ERB alpha gene by hypermethylation. Hyperimmunity drives the development of Alzheimer disease (AD). The immune system is under the circadian control, and circadian abnormalities aggravate AD progress. Here, we investigate how an AD-linked mutation deregulates expression of circadian genes and induces cognitive decline using the knock-in (KI) mice heterozygous for presenilin 2 N141I mutation. This mutation causes selective overproduction of clock gene-controlled cytokines through the DNA hypermethylation-mediated repression of REV-ERB alpha in innate immune cells. The KI/+ mice are vulnerable to otherwise innocuous, mild immune challenges. The antipsychotic chlorpromazine restores the REV-ERB alpha level by normalizing DNA methylation through the inhibition of PI3K/AKT1 pathway, and prevents the overexcitation of innate immune cells and cognitive decline in KI/+ mice. These results highlight a pathogenic link between this AD mutation and immune cell overactivation through the epigenetic suppression of REV-ERB alpha.TRU

Toward Sustaining Bioplastics: Add a Pinch of Seasoning

Modern society can no longer sustain accumulating plastic pollution without intervention; plastic waste has even found its way into the food that we consume. Unfortunately, biodegradable alternatives lack sound commercial and economic distinctiveness because mechanical strength and biodegradability are typically mutually exclusive. Inspired by fine cuisine, we introduce a novel synthetic method, referred to as "seasoning", which consists of adding a minimal amount of a biobased multifunctional monomer to pinch the amorphous domains of poly(butylene succinate). Seasoning with only 0.03 mol % of a biobased monomer led to a significantly improved oxygen barrier, high strength (86 MPa), and excellent elongation at break (654%). To the best of our knowledge, this "seasoning" approach with the significant property improvement provided is unique in the bioplastics research field. The proposed approach is highly scalable, relies on existing industrial production, and has the potential to expand current biodegradable plastic applications through its simplicity

Facile Microfluidic Fabrication of 3D hydrogel SERS Substrate with High Reusability and Reproducibility via Programmable Maskless Flow Microlithography

In the field of surface???enhanced Raman scattering (SERS), advances in nanotechnology and surface chemistry have contributed to fabricating the metal substrates with highly sophisticated architectures and strong binding affinity to target molecules which enhanced the sensitivity to target molecules. However, the elaborate yet complicated steps for the synthesis, patterning, and surface modification of metal substrates have often resulted in compromising the reliability, reproducibility, and reusability as SERS substrates. Here, a fully programmable and automated digital maskless flow microlithography process that spatiotemporally controls the fluid flow, UV irradiation, and the shape and location of SERS polymer matrix is provided to fabricate a reliable, reproducible, and reusable hydrogel???based 3D SERS substrate. The SERS substrates are located inside the microfluidic device in the form of disk???shaped hydrogels. By rationally designing the functional group chemistry of the hydrogel microposts, Ag nanoparticles are homogeneously synthesized in situ, a target molecule is amplified by 25???fold inside the microposts, and an enhancement factor as high as 2.4 ?? 108 is observed. Furthermore, a highly reusable multitarget sensing capability is demonstrated by a sequential analysis of multiple analytes without the trace of former analytes via the intermittent washing step

Dynamic multimodal holograms of conjugated organogels via dithering mask lithography

Polymeric materials have been used to realize optical systems that, through periodic variations of their structural or optical properties, interact with light-generating holographic signals. Complex holographic systems can also be dynamically controlled through exposure to external stimuli, yet they usually contain only a single type of holographic mode. Here, we report a conjugated organogel that reversibly displays three modes of holograms in a single architecture. Using dithering mask lithography, we realized two-dimensional patterns with varying cross-linking densities on a conjugated polydiacetylene. In protic solvents, the organogel contracts anisotropically to develop optical and structural heterogeneities along the third dimension, displaying holograms in the form of three-dimensional full parallax signals, both in fluorescence and bright-field microscopy imaging. In aprotic solvents, these heterogeneities diminish as organogels expand, recovering the two-dimensional periodicity to display a third hologram mode based on iridescent structural colours. Our study presents a next-generation hologram manufacturing method for multilevel encryption technologies. Periodic patterns with varying cross-linking densities are realized in conjugated polydiacetylene films, creating multiple holographic images-all dynamically responsive to exposure to various solvents-simultaneously in the same polymeric structures