Advanced in situ hydrogel assembly for guiding molecular release

Since the emergence of hydrogels as carriers for cells, bioactive molecules, and even metallic nanoparticles, there were extensive efforts to control the rate and direction of embedded molecular release, largely by additional chemical modification of gel-forming polymers. However, these approaches often encountered several challenges including the instability of molecular cargos, the extensive labor of synthesis and purification, and the uncontrollability of the molecular release direction. In contrast, many biological systems use their geometry to guide the release of their molecules or signals. Inspired by nature, this study presents unique approaches with advanced in situ formation techniques, which can overcome the problems and control the release direction and rate of the diverse embedded materials in a hydrogel. First, I demonstrated a self-folding, multi-walled poly(ethylene glycol) diacrylate (PEGDA) hydrogel tube. This tubular structure was obtained by in situ self-folding of a bi-layered PEGDA hydrogel patch constructed with gels of significantly different rigidity and expansion ratio. The radiuses of the resulting gel tubes were estimated with bilayer curvature equations and agreed with experimental data. Second, the resulting hydrogel was used to control the release rate and direction of embedded molecules by localizing the molecules in a center of the tube. A finite element method (FEM) based simulation was performed to explain the geometrical effect on controlling the molecular release. Additionally, the bilayered PEGDA hydrogel encapsulating VEGF was implanted on a chicken chorioallantoic membrane (CAM) to evaluate the neovascularization. Due to the spatiotemporal release of VEGF, the gel tubes significantly increased the density and diameters of blood vessels, compared to unfolded hydrogel patches and other ring-shaped hydrogels. Third, I presented a bio patch delivery system with minimal invasive manner by using the self-folding and unfolding technique. I assembled the hydrogel patch with a sacrificial layer that can dissolve in media after a controlled time. This hydrogel patch self-folded into a compact tube shape and delivered via a catheter to a targeted area followed by unfolding to a patch after a particular time. Lastly, I reported an in situ synthesis of metal nanoparticle-hydrogel composite that can sustainably reduce the release rate of embedded metal nanoparticles. The resulting gel composite with antimicrobial property of embedded metallic nanoparticles could control bacterial cell growth in an aqueous media and also inhibit biofilm formation on a polymeric and metallic substrates coated with the gel composite. Overall, this study was conducted for enhancing the efficacy of molecular compounds used for various agricultural products, food additives, sensor devices, and clinical treatments

Packaging and Antenna-Assembled Hybrid Stacked PCB with Novel Vertical Transition for 39 GHz 5G Base Stations

This paper proposes a novel packaging and large-scale antenna-assembled structure for a printed circuit board (PCB) that reinforces productivity, facilitates cost reduction, and maintains reliability. This was achieved by splitting the antenna from the main board and packaging it into a radio-frequency integrated circuit. In addition, two innovative solutions—an externally attachable flexible PCB antenna and a PCB-embedded coaxial line—are introduced to overcome the degradation in antenna performance and vertical RF transition loss in the proposed low-cost hybrid PCB. First, the proposed externally attachable flexible PCB antenna and a parasitic air-coupled antenna, which were easily assembled on the PCB, achieved an antenna efficiency of 95% and an impedance bandwidth of 7 GHz. Second, the fabricated coaxial line exhibited enhanced impedance matching over a wide frequency range of 30–40 GHz and improved insertion loss of approximately 1.4 dB. Furthermore, the packaged antenna, composed of 256 dual-polarized antenna elements per stream, incorporated a 39 GHz CMOS-based 16-channel phased-array transceiver IC. The set-level beam-forming measurements were verified considering an effective isotropic radiated power of 55 dBm at boresight and a steering range >±60°. In addition to being suitable for mass production in terms of cost and reliability, the proposed structures and solutions met the required antenna and beam-forming performance for commercial 39 GHz base stations without sacrificing performance

Circularly polarized antenna with folded ground and parasitic branch for 60GHz WLAN

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Matrix Rigidity-Modulated Cardiovascular Organoid Formation from Embryoid Bodies

<div><p>Stem cell clusters, such as embryoid bodies (EBs) derived from embryonic stem cells, are extensively studied for creation of multicellular clusters and complex functional tissues. It is common to control phenotypes of ES cells with varying molecular compounds; however, there is still a need to improve the controllability of cell differentiation, and thus, the quality of created tissue. This study demonstrates a simple but effective strategy to promote formation of vascularized cardiac muscle - like tissue in EBs and form contracting cardiovascular organoids by modulating the stiffness of a cell adherent hydrogel. Using collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we discovered that cellular organization in a form of vascularized cardiac muscle sheet was maximal on the gel with the stiffness similar to cardiac muscle. We envisage that the results of this study will greatly contribute to better understanding of emergent behavior of stem cells in developmental and regeneration process and will also expedite translation of EB studies to drug-screening device assembly and clinical treatments.</p></div

Analysis of stiffness-modulated contraction in EBs.

<p>(A) Percentage of contracting EBs. The difference of the values between EBs cultured on the gel with <i>E</i> of 6 kPa and other three conditions is statistically significant (*p<0.05). Values and error bars represent the mean and the standard error of at least 100 EBs, respectively. (B) Frequency of EB contractions. Values and error bars represent the mean and the standard deviation of at least 5 EBs, respectively. (C) Effects of <i>E</i> of the hydrogel on the sarcomeric α-actinin (Actn2) mRNA expression. (D) Effects of <i>E</i> of the hydrogel on cardiac troponin T type 2 (Tnnt2) mRNA expression. Values and error bars represent the mean and the standard error. In (C) and (D), * indicate statistical significance of difference between conditions (*p<0.05).</p

Cell cycle analysis of cardiomyoblasts using EdU incorporation.

<p>(A) Fluorescent images of sarcomeric α-actinin positive cells (red) incorporating EdU (green). Blue color represents cell nuclei stained by Hoechst 33342. Images represent EBs cultured in suspended state (A-1 and A-5) and on hydrogels with <i>E</i> of 0.2 (A-2 and A-5), 6 (A-3 and A-5), and 40 kPa (A-4 and A-5). Scale bar represents 20 µm. Images on the first row were taken on Day 15, and those on the second row were taken on Day 23. (B) Quantified percentage of cardiomyoblasts incorporating EdU on Day 15 (B-1) and 23 (B-2). In (B-1), the difference of values between EBs cultured on the gel with <i>E</i> of 6 kPa and 40 kPa was statistically significant (*p<0.05). In (B-2), the difference of values between EBs cultured on the gel with <i>E</i> of 6 kPa and EBs on the gels with <i>E</i> of 0.2 and 40 kPa was statistically significant (**p<0.05). Symbols ‡, ◊, †, •, *, ** and brackets indicate statistically significant groups (p<0.05). (C) The degree of decrease in the percentage of cardiomyoblasts incorporating EdU between Day 15 and Day 23.</p

Immunohistochemical analysis of cardiomyogenic and endothelial differentiation within EBs.

<p>(A) Fluorescent images of EBs stained for sarcomeric α-actinin (red) and CD31 (green). (A-1, 5, & 9) EBs cultured in suspended state for 23 days. (A-2, 6 & 10) EBs cultured on the pure collagen gel with <i>E</i> of 0.2 kPa. (A-3, 7, & 11) EBs cultured on the CCP gel with <i>E</i> of 6 kPa. (A-4 & 8) EBs cultured on the CCP gel with <i>E</i> of 40 kPa. Scale bar represents 200 µm. Images on the second row are magnified views of those on the first row. Images on the third row are three-dimensional confocal images of EBs. (B) Percentage of the EB area positively stained by antibodies to sarcomeric α-actinin. The difference of the values between EBs cultured on the gel with <i>E</i> of 6 kPa and other three conditions is statistically significant (*p<0.05). (C) Percentage of EB area positively stained with an antibody to CD31. The difference of the values between EBs cultured on the gel with <i>E</i> of 6 and 40 kPa is statistically not significant (*p>0.1). Values and error bars represent the mean and the standard error of at least 20 EBs, respectively.</p

Size analysis of EBs cultured in suspended state or on hydrogels with controlled elastic moduli.

<p>(A) Bright field images of EBs. (A-1 and A-6) EBs formed by culturing ES cells in suspended state for 8 days. (A-2 and A-7) EBs cultured in suspended state for additional 15 days. (A-3 and A-8) EBs cultured on the pure collagen gel with <i>E</i> of 0.2 kPa, (A-4 and A-9) EBs cultured on the CCP gel with <i>E</i> of 6 kPa, and (A-5 and A-10) EBs cultured on the CCP gel with <i>E</i> of 40 kPa. Images in the first and second rows represent EBs cultured in medium supplemented with 10% FBS and that without FBS, respectively. Arrows in A-1 to A-3 indicate cystic EBs. The scale bar represents 1 mm. (B) The quantified analysis of average diameters of EBs cultured in suspended state or on collagen-based hydrogels of controlled <i>E</i>. Black bars represent average diameter of EBs cultured in the medium supplemented with 10% FBS, and grey bars represent EBs cultured without FBS. Values and error bars represent the mean and the standard error of at least 50 EBs, respectively. No statistical significance was found between conditions.</p

mmWave phased-array with hemispheric coverage for 5th generation cellular handsets

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Histological analysis of EBs cultured in suspended state or on hydrogels with controlled elastic moduli.

<p>Cross-sections of EBs were stained with Hematoxylin & Eosin. (A) (A-1 and A-6) EBs formed by culturing ES cells in suspended state for 8 days. (A-2 and A-7) EBs cultured in suspended state for additional 15 days. (A-3 and A-8) EBs cultured on the pure collagen gel with <i>E</i> of 0.2 kPa, (A-4 and A-9) EBs cultured on the CCP gel with <i>E</i> of 6 kPa, and (A-5 and A-10) EBs cultured on the CCP gel with <i>E</i> of 40 kPa. Images on the first and second rows represent EBs cultured in medium supplemented with 10% FBS and that without FBS, respectively. Thin arrows in A-2, 3, and 4 indicate cystic EBs. The thick arrow in A-4 indicates columnar epithelium, and the arrowhead in A-8 indicates a neuroectodermal rosette. Scale bar represents 250 µm. (B) Quantified necrotic area percentage of EBs cultured in suspension and on hydrogels with <i>E</i> of 0.2, 6, and 40 kPa. Black bars represent average diameter of EBs cultured in media supplemented with 10% FBS and grey bars do those cultured without FBS. The difference of values for EBs cultured in the medium supplemented with 10% FBS (black bar) and free of FBS (grey bar) is statistically significant for all four different conditions (*p<0.05). Values and error bars represent the mean and the standard deviation of at least 10 EBs, respectively.</p