Publications

Micro/nanomotors (MNMs) have evolved from single self-propelled entities to versatile systems capable of performing one or multiple biomedical tasks. When single MNMs self-assemble into coordinated swarms, either under external control or triggered by chemical reactions, they offer advantages that individual MNMs cannot achieve. These benefits include intelligent multitasking and adaptability to changes in the surrounding environment. Here, we provide our perspective on the evolution of MNMs, beginning with the development of enzymatic MNMs since the first theoretical model was proposed in 2005. These enzymatic MNMs hold immense promise in biomedicine due to their advantages in biocompatibility and fuel availability. Subsequently, we introduce the design and application of single motors in biomedicine, followed by the control of MNM swarms and their biomedical applications. In the end, we propose viable solutions for advancing the development of MNM swarms and anticipate valuable insights into the creation of more intelligent and controllable MNM swarms for biomedical applications.; Micro/nanomotor swarms propelled by diverse mechanisms.

JTD Keywords: Active particles, Actuation, Behaviors, Biocompatibility, Biomedical applications, Coordination reactions, Design and application, Diffusion, External control, Medical applications, Micromotors, Motion, Nanomotors, Powered nanomotors, Propulsion, Self-assemble, Surrounding environment, Theoretical modeling, Versatile system, Viable solutions

Applications of sodium alginate (Alg) and polyacrylic acid (PAA) hydrogels in biomedicine are well-known. These are predefined by the strength and weakness of their properties, which in turn depend on the chemical structure and the architecture of their crosslinks. In this work, Alg biopolymer has been grafted to synthetic PAA that has been chemically crosslinked using N,N '-methylene-bisacrylamide (MBA) to produce a pH responsive hydrogel with adhesive property. The double crosslinking network, which combines MBA-mediated covalent crosslinks and ionic crosslinks in Alg domains, results in an elastic modulus that resembles that of highly anisotropic and viscoelastic human skin. After addressing the influence of the dual network onto the Alg-g-PAA hydrogel properties, a prospection of its potential as an adhesive has been made considering different surfaces (rubber, paper steel, porcine skin, etc). The bonding energy onto porcine skin, 32.6 +/- 4.6 J/m2, revealed that the Alg-g-PAA hydrogel can be proposed in the biomedical field as tissue adhesive for wound healing applications. Finally, the hydrogel has been semi-interpenetrated with poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-MeOH) chains through a chemical oxidative polymerization process. The resulting hydrogel, Alg-g- PAA/PEDOT-MeOH, which is even more porous than Alg-g-PAA, in addition to being electro-responsive, maintains adhesive properties.

JTD Keywords: Adhesion properties, Adhesion properties,biomedical applications,bonding energy,dual network,conducting hydrogel, Adhesive properties, Adhesives, Biomedical applications, Biopolymers, Bonding energies, Bonding energy, Chemical bonds, Conducting hydrogels, Crosslinking, Dual network, Hydrogels, Medical applications, Methylenebisacrylamide, Poly(acrylic acid), Porcine skin, Property, Rational design,film, Sodium alginate

The performance of single-chain polymeric nanoparticles (SCPNs) in biomedical applications highly depends on their conformational stability in cellular environments. Until now, such stability studies are limited to 2D cell culture models, which do not recapitulate the 3D tumor microenvironment well. Here, a microfluidic tumor-on-a-chip model is introduced that recreates the tumor milieu and allows in-depth insights into the diffusion, cellular uptake, and stability of SCPNs. The chip contains Matrigel/collagen-hyaluronic acid as extracellular matrix (ECM) models and is seeded with cancer cell MCF7 spheroids. With this 3D platform, it is assessed how the polymer's microstructure affects the SCPN's behavior when crossing the ECM, and evaluates SCPN internalization in 3D cancer cells. A library of SCPNs varying in microstructure is prepared. All SCPNs show efficient ECM penetration but their cellular uptake/stability behavior depends on the microstructure. Glucose-based nanoparticles display the highest spheroid uptake, followed by charged nanoparticles. Charged nanoparticles possess an open conformation while nanoparticles stabilized by internal hydrogen bonding retain a folded structure inside the tumor spheroids. The 3D microfluidic tumor-on-a-chip platform is an efficient tool to elucidate the interplay between polymer microstructure and SCPN's stability, a key factor for the rational design of nanoparticles for targeted biological applications.© 2024 The Authors. Small Methods published by Wiley-VCH GmbH.

JTD Keywords: 3d cancer cell uptake, Cancer cells, Cell culture, Cell uptake, Cellular uptake, Diseases, Ecm penetration, Extracellular matrices, Extracellular matrix penetration, Functional polymers, Hydrogen bonds, Medical applications, Microfluidics, Microstructure, Nanoparticles, Polymeric nanoparticles, Scpns, Single chains, Single-chain polymeric nanoparticle, Stability, Tumor-on-a-chip, Tumors

Remarkable progress in bioengineering over the past two decades has enabled the formulation of fundamental design principles for a variety of medical and non-medical applications. These advancements have laid the foundation for building multicellular engineered living systems (M-CELS) from biological parts, forming functional modules integrated into living machines. These cognizant design principles for living systems encompass novel genetic circuit manipulation, self-assembly, cell–cell/matrix communication, and artificial tissues/organs enabled through systems biology, bioinformatics, computational biology, genetic engineering, and microfluidics. Here, we introduce design principles and a blueprint for forward production of robust and standardized M-CELS, which may undergo variable reiterations through the classic design-build-test-debug cycle. This Review provides practical and theoretical frameworks to forward-design, control, and optimize novel M-CELS. Potential applications include biopharmaceuticals, bioreactor factories, biofuels, environmental bioremediation, cellular computing, biohybrid digital technology, and experimental investigations into mechanisms of multicellular organisms normally hidden inside the “black box” of living cells.

JTD Keywords: cell-fate specification, endothelial-cells, escherichia-coli, extracellular-matrix, gene-expression noise, nuclear hormone-receptors, pluripotent stem-cells, primitive endoderm, transcription factors, Artificial tissues, Assembly cells, Biological parts, Biological systems, Bioremediation, Blood-brain-barrier, Cell engineering, Cell/matrix communication, Design principles, Environmental technology, Functional modules, Fundamental design, Genetic circuits, Genetic engineering, Living machines, Living systems, Medical applications, Molecular biology, Synthetic biology

JTD Keywords: amino-acids, catalysis, dopant-free hydroxyapatite, electrical properties, electrophotosynthesis, nitrogen, thermally-stimulated polarization, Advanced materials, Biocompatibility, Biomedical applications, Brushite, Doped hydroxyapatites, Electric voltage, Electrical characterization, Electrochemical impedance spectroscopy, Equivalent circuits, Future perspectives, Highest temperature, Hydroxyapatite, Interfaces (materials), Material interfaces, Medical applications, Polarization, Polarization conditions, Surface-charges, Technological applications

Flexible electrochemical sensors based on electroactive materials have emerged as powerful analytical tools for biomedical applications requiring bioanalytes detection. Within this context, 3D printing is a remarkable technology for developing electrochemical devices, due to no design constraints, waste minimization, and batch manufacturing with high reproducibility. However, the fabrication of 3D printed electrodes is still limited by the in-house fabrication of conductive filaments, which requires the mixture of the electroactive material with melted of thermoplastic polymer (e.g., polylactic acid, PLA). Herein, a simple approach is presented for preparing electrochemical dopamine (DA) biosensors. Specifically, the surface of 3D-printed PLA specimens, which exhibit an elastic modulus and a tensile strength of 3.7 +/- 0.3 GPa and 47 +/- 1 MPa, respectively, is activated applying a 0.5 m NaOH solution for 30 min and, subsequently, poly(3,4-ethylenedioxythiophene) is polymerized in situ using aqueous solvent. The detection of DA with the produced sensors has been demonstrated by cyclic voltammetry, differential pulse voltammetry, and chronoamperometry. In summary, the obtained results reflect that low-cost electrochemical sensors, which are widely used in medicine and biotechnology, can be rapidly fabricated using the proposed approach that, although based on additive manufacturing, does not require the preparation of conductive filaments.

JTD Keywords: 3d printers, Additive manufacturing, Amines, Batch manufacturing, Biomedical applications, Chronoamperometry, Conducting polymer, Conducting polymers, Conductive filaments, Conservation, Cyclic voltammetry, Differential pulse voltammetry, Electroactive material, Electrochemical biosensor, Electrochemical devices, Electrochemical sensors, Electrodes, Electron emission, Flexible electrode, High reproducibility, Medical applications, Neurophysiology, Poly-3 ,4-ethylenedioxythiophene, Polyesters, Polylactic aci, Sodium hydroxide, Tensile strength, Thermoplastic polymer

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on-demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms. A considerable research effort has gone into demonstrating that MNMs possess the potential of biomedical cargo loading, transportation, and targeted release to achieve therapeutic functions. Herein, the recent advances of self-propelled MNMs for on-demand biomedical cargo transportation, including their self-propulsion mechanisms, guidance strategies, as well as proof-of-concept studies for biological applications are presented. In addition, some of the major challenges and possible opportunities of MNMs are identified for future biomedical applications in the hope that it may inspire future research.

JTD Keywords: Biomedical applications, Cargo transportation, Guidance strategies, Micro/nanomotors, Self-propulsion

Emerging nanobiotechnologies can offer solutions to the current and future challenges in medicine. By covering topics from regenerative medicine, tissue engineering, drug delivery, bionanofabrication, and molecular biorecognition, this Special Issue aims to provide an update on the trends in nanomedicine and drug delivery using biomimetic approaches, and the development of novel biologically inspired devices for the safe and effective diagnosis, prevention, and treatment of disease.

JTD Keywords: Bioinspired nanotechnologies, Bionanofabrication, Bio-nano measurement and microscopy, Nanomaterials for biological and medical applications, Nanoassemblies, Nanostructured surfaces, Drug delivery, Nanobioelectronics, Integrated systems/nanobiosensors, Nanotoxicology, Graphene-based applications

Poly(vinylchloride) (PVC) is the most common polymer matrix used in the fabrication of ion-selective electrodes (ISEs). However, the surfaces of PVC-based sensors have been reported to show membrane instability. In an attempt to overcome this limitation, here we developed two alternative methods for the preparation of highly stable and robust ion-selective sensors. These platforms are based on the selective electropolymerization of poly(3,4-ethylenedioxythiophene) (PEDOT), where the sulfur atoms contained in the polymer covalently interact with the gold electrode, also permitting controlled selective attachment on a miniaturized electrode in an array format. This platform sensor was improved with the crosslinking of the membrane compounds with poly(ethyleneglycol) diglycidyl ether (PEG), thus also increasing the biocompatibility of the sensor. The resulting ISE membranes showed faster signal stabilization of the sensor response compared with that of the PVC matrix and also better reproducibility and stability, thus making these platforms highly suitable candidates for the manufacture of robust implantable sensors.

JTD Keywords: Biomedicine, Electrochemistry, Endoscope, Implantable device, Ion-selective electrode (ISE) sensor, Ischemia, pH detection, Biocompatibility, Chemical sensors, Electrochemistry, Electrodes, Electropolymerization, Endoscopy, Functional polymers, Implants (surgical), Ion selective electrodes, Medical applications, Polyvinyl chlorides, Stabilization, Biomedical applications, Biomedicine, Implantable devices, Ion selective sensors, Ischemia, Membrane instability, pH detection, Poly(3 ,4 ethylenedioxythiophene) (PEDOT), Ion selective membranes

This paper reviews commonly used methods of analyzing and interpreting friction, adhesion and nanoindentation with an AFM tip test data, with a particular emphasis of the testing of single crystals, metals, ceramics and ceramic coatings. Experimental results are reported on the friction, mechanical and adhesion properties of these materials. The popularity of AFM testing is evidenced by the large quantity of papers that report such measurements in the last decade. Unfortunately, a lot of information about these topics is scare in the literature. The present paper is aimed to present the basic physical modelling employed and also some examples using each technique.

JTD Keywords: Mechanical properties, Plasticity, Biomedical applications, Engine components

Continuous advances on diagnostic techniques based on medical images, as well as the incorporation of new techniques in surgical instruments are progressively changing the new surgical procedures. Also, new minimally invasive techniques, which are currently highly consolidated, have produced significant advances, both from the technological and from the surgical treatment perspectives. The limitations that the manual realization of surgical interventions implies, in what refers to precision and accessibility, can be tackled with the help of robotics. In the same way, sensor based robot control techniques are opening new possibilities for the introduction of more improvements in these procedures, either relying on teleoperation, in which the surgeon and the robot establish their best synergy to get the optimal results, or by means of the automation of some specific actions or tasks. In this article the effect of robotics in the evolution of surgical techniques is described. Starting with a review of the robotics application fields, the article continues analyzing the methods and technologies involved in the process of robotizing surgical procedures, as well as the surgeon-robot interaction systems.

JTD Keywords: Robotics, Medical Applications, Teleoperation, Biomedical Systems, Computer Aided Surgery, Human-Machine Interaction

Polymers with high glass transition temperatures, fluorinated ethylene propylene copolymer (FEP) and poly(ethylene naphthalate) (PEN), have been used in imprint lithography as a protective support layer and as a secondary mould, to imprint superficial structures into a polymer with a lower glass transition temperature, namely poly(methyl methacrylate) (PMMA). As a support layer, FEP replaces fragile silicon based supports for the production of freestanding, structured sheets of PMMA, useful, for example, in biomedical applications where transmittance optical microscopy is required. Secondary PEN moulds, produced by imprinting using silicon-based primary moulds, have been used to transfer sub-micrometer tall structures to a freestanding PMMA sheet. Similarly, hole structures, with different dimensions, have been embossed in both sides of a PMMA sheet simultaneously.

JTD Keywords: Polymer engineering, Embossing, Nanoimprint lithography, Biomedical applications