Publications

Gold nanoparticles (GNP) are highly valuable in nanotechnology due to their biocompatibility and unique physicochemical properties, which make them attractive as nanocarriers for targeted drug delivery. In the context of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), GNP hold promise for reducing the toxicity of Amyloid-beta peptide (A beta) aggregates. However, a major challenge in developing new therapies for NDDs lies in the limited reliance on animal models and the difficulty of crossing the blood-brain barrier (BBB). This study investigates the effects of GNP on A beta toxicity using a human-based BBB-organ-on-a-chip model (BBBoC), mimicking the 3D cellular architecture of the BBB under both normal and pathological conditions. We rationally designed a novel nanosystem functionalized with the peptide D3, which functions both as a selective A beta toxicity inhibitor and a BBB-targeting agent. The results show that GNP can cross the BBB, reduce the A beta- induced cytotoxicity, and promote the maintenance of the BBB integrity. Moreover, controlling the shape of GNP further enhanced their protective effect. Overall, this work highlights the feasibility of rationally designed GNP as a promising therapeutic strategy for AD, evaluated through a more reliable and predictive human-relevant model.

JTD Keywords: Alzheimer's disease, Amyloid-beta peptide, Arginine-rich, Blood-brain barrier, Elegans, Endothelial-cells, Gold nanoparticles, Hypothesis, Impact, Integrity, Microfluidic, Nanorods, Oligomers, Organ-on-a-chip, Permeability, Toxicity

© 2021 Elsevier B.V. The blood-brain barrier (BBB) is a dynamic cellular barrier that regulates brain nutrient supply, waste efflux, and paracellular diffusion through specialized junctional complexes. Finding a system to mimic and monitor BBB integrity (i.e., to be able to assess the effect of certain compounds on opening or closing the barrier) is of vital importance in several pathologies. This work aims to overcome some limitations of current barrier integrity measuring techniques thanks to a multi-layer microfluidic platform with integrated electrodes and Multi-frequency Trans-Endothelial Electrical Resistance (MTEER) in synergy with machine learning algorithms. MTEER measurements are performed across the barrier in a range of frequencies up to 10 MHz highlighting the presence of information on different frequency ranges. Results show that the proposed platform can detect barrier formation, opening, and regeneration afterwards, correlating with the results obtained from immunostaining of junctional complexes. This model presents novel techniques for a future biological barrier in-vitro studies that could potentially help on elucidating barrier opening or sealing on treatments with different drugs.

JTD Keywords: blood-brain barrier, cellular barrier integrity monitoring, impedance sensors, machine learning, microelectrodes, mteer, rapid prototyping, Blood-brain barrier, Cellular barrier integrity monitoring, Electrical impedance spectroscopy, Impedance sensors, Machine learning, Microelectrodes, Mteer, Rapid prototyping

Bioinspired hybrid soft robots that combine living and synthetic components are an emerging field in the development of advanced actuators and other robotic platforms (i.e., swimmers, crawlers, and walkers). The integration of biological components offers unique characteristics that artificial materials cannot precisely replicate, such as adaptability and response to external stimuli. Here, we present a skeletal muscle–based swimming biobot with a three-dimensional (3D)–printed serpentine spring skeleton that provides mechanical integrity and self-stimulation during the cell maturation process. The restoring force inherent to the spring system allows a dynamic skeleton compliance upon spontaneous muscle contraction, leading to a cyclic mechanical stimulation process that improves the muscle force output without external stimuli. Optimization of the 3D-printed skeletons is carried out by studying the geometrical stiffnesses of different designs via finite element analysis. Upon electrical actuation of the muscle tissue, two types of motion mechanisms are experimentally observed: directional swimming when the biobot is at the liquid-air interface and coasting motion when it is near the bottom surface. The integrated compliant skeleton provides both the mechanical self-stimulation and the required asymmetry for directional motion, displaying its maximum velocity at 5 hertz (800 micrometers per second, 3 body lengths per second). This skeletal muscle–based biohybrid swimmer attains speeds comparable with those of cardiac-based biohybrid robots and outperforms other muscle-based swimmers. The integration of serpentine-like structures in hybrid robotic systems allows self-stimulation processes that could lead to higher force outputs in current and future biomimetic robotic platforms. Copyright © 2021 The Authors, some rights reserved;

JTD Keywords: actuators, design, fabrication, mechanics, mems, myotubes, platform, tissue, 3d printers, Agricultural robots, Animals, Artificial organs, Biological components, Biomimetic materials, Biomimetic processes, Biomimetics, Cell line, Electrical actuation, Equipment design, Finite element analysis, Geometrical stiffness, Intelligent robots, Liquefied gases, Liquid-air interface, Mechanical integrity, Mechanical phenomena, Mechanical stimulation, Mice, Motion, Muscle, Muscle contractions, Muscle, skeletal, Phase interfaces, Printing, three-dimensional, Robotics, Serpentine, Smart materials, Springs (components), Swimming, Threedimensional (3-d), Tissue scaffolds