Biology subjects

Guix, M.

Publications and source records attributed to Guix, M..

6 recordsLinked to original sources

bioRxiv2024

Bioengineering Fascicle-like Skeletal Muscle Bioactuators via Pluronic-Assisted Co-axial 3D Bioprinting

Advances in 3D bioprinting have opened new possibilities in the development of bioengineered muscle models that mimic the structure and functionality of native tissues. The combination of skeletal muscle tissue and artificial elements promotes diverse innovative solutions of interest in both the biomedical field and the development of biohybrid actuators. However, current bioengineering approaches do not fully recreate the complex fascicle-like hierarchical organization of skeletal muscle, impacting on the muscle maturation process due to a lack of oxygen and nutrients supply in the scaffold inner regions. Here we explored co-axial 3D bioprinting as a strategy towards overcoming this challenge, creating individual/non-fused filaments with controlled thickness that present a fascicle-like organization. Compared to conventional 3D-bioprinting, where cell-laden bioink is disposed by a single syringe, our Pluronic-assisted co-axial 3D-bioprinting system (PACA-3D) creates a physical confinement of the bioink during the extrusion process, effectively obtaining thin and independent printed fibers with controlled shape. Fabrication of skeletal muscle-based actuators with PACA-3D resulted in improved cell differentiation, obtaining stronger bioactuators with increased force output when compared to bioactuators fabricated by conventional 3D bioprinting. The versatility of our technology has been demonstrated using different biomaterials, showing its potential to develop more complex biohybrid tissue-based architectures with improved functionality.

bioengineering↗

bioRxiv2022

Improved performance of biohybrid muscle-based bio-bots doped with piezoelectric boron nitride nanotubes

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, we integrate boron nitride nanotubes (BNNTs), with piezoelectric properties, in muscle-based bio-bots and demonstrate an improvement in their force output and motion speed. We provide a full characterization of the BNNTs, and we confirm their piezoelectric behavior with piezometer and dynamometer measurements. We hypothesize that the improved performance is a result of an electric field generated by the nanocomposites due to stresses produced by the cells during differentiation, which in turns improves their maturation. We back this hypothesis with finite element simulations supporting that this stress can generate a non-zero electric field within the matrix. With this work, we show that the integration of nanocomposite into muscle-based bio-bots can improve their performance, paving the way towards stronger and faster bio-hybrid robots.

bioengineering↗

bioRxiv2021

Chemotherapy induces a YAP1-dependent fetal conversion to human Colorectal Cancer cells that is predictive of poor patient outcome

Current therapy against colorectal cancer is based on DNA-damaging agents that eradicate highly proliferative malignant cells. Whether sublethal chemotherapy affects tumor cell behavior and impacts on patient outcome is primarily unstudied. We now show that sublethal chemotherapy imposes a quiescent-like state to p53 wildtype human colorectal cancer (CRC) cells that is linked to the acquisition of a fetal phenotype downstream of YAP1, similar to that observed after intestinal damage. CRC cells displaying this fetal phenotype exhibit tumor- initiating activity comparable to untreated cells but superior metastatic capacity. Notably, nuclear YAP1 accumulation, or detection of the fetal signature in tumors predict poor prognosis in CRC patients carrying p53 wildtype tumors. Collectively, our results uncover a potential adverse response of tumor cells to suboptimal chemotherapy, and identify nuclear YAP1 and fetal conversion of colorectal tumors as biomarkers for prognosis and therapy prescription. Statement of significanceChemotherapy induces a quiescent-like phenotype to colorectal cancer cells that is linked to the acquisition of a YAP1-dependent fetal signature. Notably, this signature is predictive of patient outcome in different cohorts of human colorectal cancer.

cancer biology↗

bioRxiv2020

Bio-hybrid soft robots with self-stimulating skeletons

Bioinspired hybrid soft robots combining living actuation and synthetic components are an emerging field in the development of advanced actuators and other robotic platforms (i.e. swimmers, crawlers, walkers). The integration of biological components offers unique properties (e.g. adaptability, response to external stimuli) that artificial materials cannot replicate with accuracy, being skeletal and cardiac muscle cells the preferred candidates for providing contractile actuation. Here, we present a skeletal-muscle-based swimming biobot with a 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 novel 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: i) directional swimming when the biobot is at the liquid-air interface and ii) 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 Hz (800 micrometer second-1, 3 body length second-1). This skeletal muscle-based bio-hybrid swimmer attains speeds comparable to cardiac-based bio-hybrid 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.

bioengineering↗

bioRxiv2020

Monitoring the collective behavior of enzymatic nanomotors in vitro and in vivo by PET-CT

Enzyme powered nanomotors hold great potential for biomedical applications, as they show improved diffusion and navigation within biological environments using endogenous fuels. Yet, understanding their collective behavior and tracking them in vivo is paramount for their clinical translation. Here, we report on the in vitro and in vivo study of swarms of self-propelled enzyme-nanomotors and the effect of collective behavior on the nanomotors distribution within the bladder. For that purpose, mesoporous silica nanomotors were functionalized with urease enzymes and gold nanoparticles. Two radiolabeling strategies, i.e. absorption of 124I on gold nanoparticles and covalent attachment of an 18F-labeled prosthetic group to urease, were assayed. In vitro experiments using optical microscopy and positron emission tomography (PET) showed enhanced fluid mixing and collective migration of nanomotors in phantoms containing complex paths. Biodistribution studies after intravenous administration in mice confirmed the biocompatibility of the nanomotors at the administered dose, the suitability of PET to quantitatively track nanomotors in vivo, and the convenience of the 18F-labeling strategy. Furthermore, intravesical instillation of nanomotors within the bladder in the presence of urea resulted in a homogenous distribution after the entrance of fresh urine. Control experiments using BSA-coated nanoparticles or nanomotors in water resulted in sustained phase separation inside the bladder, demonstrating that the catalytic decomposition of urea can provide urease-nanomotors with active motion, convection and mixing capabilities in living reservoirs. This active collective dynamics, together with the medical imaging tracking, constitutes a key milestone and a step forward in the field of biomedical nanorobotics, paving the way towards their use in theranostic applications.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

bioRxiv2020

3D-printed drug testing platform based on a 3D model of aged human skeletal muscle

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 modelling, the bioengineered muscle is treated with tumor necrosis factor to mimic the conditions of aging, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline(R) 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.

bioengineering↗