Staff member publications
Lai, Stefano, Fuentes, Judith, Guix, Maria, Casula, Giulia, Cosseddu, Piero, Sanchez, Samuel, (2024). Real-Time Force Monitoring of Electrically Stimulated 3D-Bioengineered Muscle Bioactuators Using Organic Sensors with Tunable Sensitivity Advanced Intelligent Systems , 2400407
The contractile nature of skeletal muscle tissue makes it especially attractive for powering biohybrid actuators. Significant efforts have been dedicated to the improvement and control of contraction force, going one step forward toward the automation of these biohybrid platforms. Herein, 3D-bioengineered skeletal muscle tissues are integrated with organic transistor-based sensors to define a soft bioactuator with real-time force monitoring capabilities. The muscle tissue is electrically stimulated while the organic sensor ensures transduction of the exerted force into an electrical signal that allows direct monitoring of the bioactuator performance. Sensor calibration is carried out to define its sensitivity at different biasing conditions: as opposed to standard, two-terminal piezoresistive devices, transistor-based strain sensors show tunable sensitivity by acting on the voltage applied to a third terminal-the gate. A complete evaluation of sensing performances is provided, demonstrating that real-time monitoring is effective under different conditions, including stimulation signal frequency and chemical modulation of the bioactuator contraction, demonstrating its potential use as a drug testing platform. In the reported results, the way is paved for a complete exploitation of organic devices in soft robotic applications and to the development of novel biohybrid machines in bioengineering and biomedicine. The integration of sensing elements in bioengineered actuators is key to obtain real-time information about their performance and further control/automation. By coupling flexible organic field-effect transistor to a skeletal muscle actuator we demonstrate the feasibility to record in real-time its contractile behavior when stimulated by electrical pulses, showing both high sensitivity absence of cross talk between stimulation and readout.image (c) 2024 WILEY-VCH GmbH
JTD Keywords: Bioengineerings, Flexible electronics, Muscle-based actuators, Organic field-effect transistors, Soft robotic
Molina, Brenda G, Fuentes, Judith, Aleman, Carlos, Sanchez, Samuel, (2024). Merging BioActuation and BioCapacitive properties: A 3D bioprinted devices to self-stimulate using self-stored energy Biosensors & Bioelectronics 251, 116117
Biofabrication of three-dimensional (3D) cultures through the 3D Bioprinting technique opens new perspectives and applications of cell-laden hydrogels. However, to continue with the progress, new BioInks with specific properties must be carefully designed. In this study, we report the synthesis and 3D Bioprinting of an electroconductive BioInk made of gelatin/fibrinogen hydrogel, C2C12 mouse myoblast and 5% w/w of conductive poly (3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs). The influence of PEDOT NPs, incorporated in the cellladen BioInk, not only showed a positive effect in cells viability, differentiation and myotube functionalities, also allowed the printed constructs to behaved as BioCapacitors. Such devices were able to electrochemically store a significant amount of energy (0.5 mF/cm2), enough to self-stimulate as BioActuator, with typical contractions ranging from 27 to 38 mu N, during nearly 50 min. The biofabrication of 3D constructs with the proposed electroconductive BioInk could lead to new devices for tissue engineering, biohybrid robotics or bioelectronics.
JTD Keywords: 3d bioprinting, Animal, Animals, Bioactuator, Bioactuators, Biocapacitor, Biofabrication, Bioprinting, Biosensing techniques, C2c12 myoblasts, Cells, Chemistry, Electric conductivity, Electroconductive, Electroconductive bioink, Ethylenedioxythiophenes, Genetic procedures, Hydrogel, Hydrogels, Mice, Mouse, Pedot nps, Pedot nps,3d bioprinting,electroconductive bioink,bioactuator,biocapacito, Poly (3,4-ethylenedioxythiophene) nanoparticle, Printing, three-dimensional, Procedures, Skeletal-muscle,cytotoxicity,polymer, Synthesis (chemical), Three dimensional printing, Tissue engineering, Tissue scaffolds
Mestre, R, Fuentes, J, Lefaix, L, Wang, JJ, Guix, M, Murillo, G, Bashir, R, Sanchez, S, (2023). Improved Performance of Biohybrid Muscle-Based Bio-Bots Doped with Piezoelectric Boron Nitride Nanotubes Advanced Materials Technologies 8,
Biohybrid robots, or bio-bots, integrate living and synthetic materials following a synergistic strategy to acquire some of the unique properties of biological organisms, like adaptability or bio-sensing, which are difficult to obtain exclusively using artificial materials. Skeletal muscle is one of the preferred candidates to power bio-bots, enabling a wide variety of movements from walking to swimming. Conductive nanocomposites, like gold nanoparticles or graphene, can provide benefits to muscle cells by improving the scaffolds' mechanical and conductive properties. Here, boron nitride nanotubes (BNNTs), with piezoelectric properties, are integrated in muscle-based bio-bots and an improvement in their force output and motion speed is demonstrated. A full characterization of the BNNTs is provided, and their piezoelectric behavior with piezometer and dynamometer measurements is confirmed. It is hypothesized that the improved performance is a result of an electric field generated by the nanocomposites due to stresses produced by the cells during differentiation. This hypothesis is backed with finite element simulations supporting that this stress can generate a non-zero electric field within the matrix. With this work, it is shown that the integration of nanocomposite into muscle-based bio-bots can improve their performance, paving the way toward stronger and faster bio-hybrid robots.
JTD Keywords: Bio-bots, Biohybrid robots, Biomaterials, Boron nitride nanotubes, Cells, Cytotoxicity, Differentiation, Myoblasts, Skeletal muscle tissue, Skeletal-muscle, Stimulation
Mestre, R, García, N, Patiño, T, Guix, M, Fuentes, J, Valerio-Santiago, M, Almiñana, N, Sánchez, S, (2021). 3D-bioengineered model of human skeletal muscle tissue with phenotypic features of aging for drug testing purposes Biofabrication 13, 45011
Three-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modeling, the bioengineered muscle is treated with tumor necrosis factor α to mimic the conditions of aging, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline® Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.
JTD Keywords: 3d bioprinting, bio-actuator, drug testing, human skeletal muscle, muscle ageing, platform, tnf-alpha, 3d bioprinting, Bio-actuator, Drug testing, Human skeletal muscle, Muscle ageing, Necrosis-factor-alpha
Veronika Magdanz, Arnau Llobera, Judith Fuentes, Dalia Mahdy, Islam S. M. Khalil, Maria Guix, Samuel Sanchez, (2021). 3D printed magnet robots for cell delivery with tuned flexibility 25th International Conference On Miniaturized Systems For Chemistry And Life Sciences, µTas 2021 ,
Magnetically actuated microrobots have the potential to make medical operations less invasive, more precise and remotely controlled. Therefore, they are promising for many applications such as targeted therapy or minimally invasive surgeries. Current challenges in the field of magnetic microrobotics include efficient propulsion and biocompatibility. This article addresses both of these aspects and aims to optimize the flexibility of a soft magnetic swimmer by tuning its material properties, define different magnetic segments and investigate its biocompatibility and potential as cell delivery machine.
JTD Keywords: 3d printing, Elastómeros, Sensores remotos
Guix, M, Mestre, R, Patiño, T, De Corato, M, Fuentes, J, Zarpellon, G, Sánchez, S, (2021). Biohybrid soft robots with self-stimulating skeletons Science Robotics 6, eabe7577
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, Biological components, Biomimetic processes, Electrical actuation, Geometrical stiffness, Intelligent robots, Liquefied gases, Liquid-air interface, Mechanical integrity, Mechanical stimulation, Muscle, Muscle contractions, Phase interfaces, Robotics, Serpentine, Springs (components), Threedimensional (3-d)