Microfluidic Platforms for Evaluation of Nanobiomaterials: a Review

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Microfluidic Platforms for Evaluation of Nanobiomaterials: A Review

Biomaterials, especially those based on nanomaterials, have emerged as critical tools in biomedical applications. The applications encompass a wide range such as implantable devices, tissue regeneration, drug delivery, diagnostic systems, and molecular printing. The type of materials used also covers a wide range: metals (permanent and degradable), polymers (permanent and degradable), carbon nanotubes, and lipid nanoparticles. This paper explores the use of microfluidic platforms as a high-throughput research tool for the evaluation of nanobiomaterials. Typical screening of such materials involves cell/tissue cultures to determine attributes such as cell adhesion, proliferation, differentiation, as well as biocompatibility. In addition to this, other areas such as drug delivery and toxicity can also be evaluated via microfluidics. Traditional approach for screening of such materials is very time-consuming, and a lot of animals should be sacrificed since it involves one material and a single composition or concentration for a single test. The microfluidics approach has the advantage of using multiple types of drugs and their concentration gradients to simultaneously study the effect on the nanobiomaterial and its interaction with cell/tissue. In addition to this, microfluidics provides a unique environment to study the effect of cell-to-extracellular interaction and cell-to-cell communication in the presence of the nanobiomaterials

The Effects of Primary Oxy-Salts on Anodizing Magnesium Alloy AZ91D

Anodization is known to be an effective way to slow down the initial corrosion rate of magnesium (Mg) and its alloys. Here, we investigated the specific use of oxy-salts to improve the corrosion resistance of anodizing coatings. Oxy-salts of silicate, phosphate, and carbonate were added separately to a sodium hydroxide alkaline electrolyte used to anodize Mg alloy AZ91D. The process was investigated in terms of anodizing behavior, the surface properties, and the corrosion behavior of AZ91D. Anodizing AZ91D using the silicate- containing electrolyte generated sparks, and produced a thicker and more corrosion-resistant layer than the other oxy-salts. In the process, MgO and SiO2 formed Mg2SiO4 at high temperatures. Coatings from the phosphate- and carbonate- containing electrolyte anodizations did not contain phosphorus or carbon. We also studied the effects of silicate concentration on the corrosion resistance and properties of the surface

An evaluation of the sonoporation potential of low-boiling point phase-change ultrasound contrast agents in vitro

Abstract Background Phase-change ultrasound contrast agents (PCCAs) offer a solution to the inherent limitations associated with using microbubbles for sonoporation; they are characterized by prolonged circulation lifetimes, and their nanometer-scale sizes may allow for passive accumulation in solid tumors. As a first step towards the goal of extravascular cell permeabilization, we aim to characterize the sonoporation potential of a low-boiling point formulation of PCCAs in vitro. Methods Parameters to induce acoustic droplet vaporization and subsequent microbubble cavitation were optimized in vitro using high-speed optical microscopy. Sonoporation of pancreatic cancer cells in suspension was then characterized at a range of pressures (125–600 kPa) and pulse lengths (5–50 cycles) using propidium iodide as an indicator molecule. Results We achieved sonoporation efficiencies ranging from 8 ± 1% to 36 ± 4% (percent of viable cells), as evidenced by flow cytometry. Increasing sonoporation efficiency trended with increasing pulse length and peak negative pressure. Conclusions We conclude that PCCAs can be used to induce the sonoporation of cells in vitro, and our results warrant further investigation into the use of PCCAs as extravascular sonoporation agents in vivo

Studying the Inflammatory Responses to Amyloid Beta Oligomers in Brain-Specific Pericyte and Endothelial Co-Culture From Human Stem Cells

Background: Recently, the in vitro blood–brain barrier (BBB) models derived from human pluripotent stem cells have been given extensive attention in therapeutics due to the implications they have with the health of the central nervous system. It is essential to create an accurate BBB model in vitro in order to better understand the properties of the BBB, and how it can respond to inflammatory stimulation and be passed by targeted or non-targeted cell therapeutics, more specifically extracellular vesicles.Methods: Brain-specific pericytes (iPCs) were differentiated from iPSK3 cells using dual SMAD signaling inhibitors and Wnt activation plus fibroblast growth factor 2 (FGF-2). The derived cells were characterized by immunostaining, flow cytometry, and RT-PCR. In parallel, blood vessels organoids were derived using Wnt activation, BMP4, FGF2, VEGF, and SB431542. The organoids were replated and treated with retinoic acid to enhance the blood–brain barrier (BBB) features in the differentiated brain endothelial cells (iECs). Co-culture was performed for iPCs and iECs in the transwell system and 3D microfluidics channels.Results: The derived iPCs expressed common markers PDGFRb and NG2, and brain-specific genes FOXF2, ABCC9, KCNJ8, and ZIC1. The derived iECs expressed common endothelial cell markers CD31, VE-cadherin, and BBB-associated genes BRCP, GLUT-1, PGP, ABCC1, OCLN, and SLC2A1. The co-culture of the two cell types responded to the stimulation of amyloid β42 oligomers by the upregulation of the expression of TNFa, IL6, NFKB, Casp3, SOD2, and TP53. The co-culture also showed the property of trans-endothelial electrical resistance. The proof of concept vascularization strategy was demonstrated in a 3D microfluidics-based device.Conclusion: The derived iPCs and iECs have brain-specific properties, and the co-culture of iPCs and iECs provides an in vitro BBB model that show inflammatory response. This study has significance in establishing micro-physiological systems for neurological disease modeling and drug screening

Carbon Nanotube Paper-Based Electroanalytical Devices

Here, we report on carbon nanotube paper-based electroanalytical devices. A highly aligned-carbon nanotube (HA-CNT) array, grown using chemical vapor deposition (CVD), was processed to form bi-layered paper with an integrated cellulose-based Origami-chip as the electroanalytical device. We used an inverse-ordered fabrication method from a thick carbon nanotube (CNT) sheet to a thin CNT sheet. A 200-layered HA-CNT sheet and a 100-layered HA-CNT sheet are explored as a working electrode. The device was fabricated using the following methods: (1) cellulose-based paper was patterned using a wax printer, (2) electrical connection was made using a silver ink-based circuit printer, and (3) three electrodes were stacked on a 2D Origami cell. Electrochemical behavior was evaluated using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). We believe that this platform could attract a great deal of interest for use in various chemical and biomedical applications

A Smartphone-Based Automatic Measurement Method for Colorimetric pH Detection Using a Color Adaptation Algorithm

This paper proposes a smartphone-based colorimetric pH detection method using a color adaptation algorithm for point-of-care applications. Although a smartphone camera can be utilized to measure the color information of colorimetric sensors, ambient light changes and unknown built-in automatic image correction operations make it difficult to obtain stable color information. This paper utilizes a 3D printed mini light box and performs a calibration procedure with a paper-printed comparison chart and a reference image which overcomes the drawbacks of smartphone cameras and the difficulty in preparing for the calibration procedure. The color adaptation is performed in the CIE 1976 u’v’ color space by using the reference paper in order to stabilize the color variations. Non-rigid u’v’ curve interpolation is used to produce the high-resolution pH estimate. The final pH value is estimated by using the best-matching method to handle the nonlinear curve properties of multiple color patches. The experimental results obtained using a pH indicator paper show that the proposed algorithm provides reasonably good estimation of pH detection. With paper-printed accurate color comparison charts and smart color adaptation techniques, superior estimation is achieved in the smartphone-based colorimetric pH detection system for point-of-care application

Mechanically Tunable Extracellular Matrix of Genipin Crosslinked Collagen and Its Effect on Endothelial Function

Mechanical rigidity of a matrix, to which cells adhere, plays a significant role in regulating phenotypic cellular behaviors such as spreading and junction formation because vascular cells sense and respond to changes in their mechanical environment. Controlling mechanical properties of extracellular matrix by using a crosslinker is important for cell and tissue mechanobiology. In this paper, we explored genipin, a natural plant extract, to crosslink collagen-I in order to enhance mechanical properties with low cytotoxicity. We characterized the effects of genipin concentration on the mechanical properties, color change, degradation, structure, cell viability, and endothelial function such as transendothelial electrical resistance (TEER). Through the analysis of both material properties and endothelial response, it was found that genipin-based glycation caused an increase in viscoelastic moduli in collagen hydrogels, as well as increased fiber density in their structural morphology. Endothelial cells were found to form better barriers, express higher levels of tight junction proteins, and exhibit better adhesion on stiffer matrices