Publications

The transition from insulator to electro-responsive has been successfully achieved by earlier studies for some inorganic materials by applying external stimuli that modify their 3D and/or electronic structures. In the case of insulating polymers, this transition is frequently accomplished by mixing them with other electroactive materials, even though a few physical treatments that induce suitable chemical modifications have also been reported. In this work, a smart approach based on the application of an electro-thermal reorientation process followed by a charged gas activation treatment has been developed for transforming insulating 3D printed polymers into electro-responsive materials. First, the developed procedure has been exhaustively investigated for 3D printed poly(lactic acid) (PLA) and subsequently has been extended to 3D printed polypropylene (PP) and poly(ethylene terephthalate glycol) (PETG) specimens. FTIR and Raman spectroscopies, X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, and water contact angle measurements confirmed that, while the electro-thermal reorientation mainly promotes the crystallinity of the samples, the charged gas activation oxidizes the C-O bonds at the surface and consequently modifies the surface morphology and wettability. Furthermore, cyclic voltammetry assays demonstrated that treated PLA, PP, and PETG are electro-responsive, even though the electrochemical activity was much higher for oxygen-containing polymers (PLA and PETG) than for the oxygen-free one (PP). Finally, as a proof of concept, treated 3D printed PLA specimens have been used as electrochemical sensors to detect dopamine (DA), an important neurotransmitter, in a concentration interval ranging from 50 to 1000 mu M. The peak associated with the oxidation from DA to dopaminoquinone and the linearity of the calibration plot, which was constructed using the anodic peak current, proved that treated PLA is not only electro-responsive but also able to electrocatalyze the oxidation of DA.

JTD Keywords: 3d printin, Blends, Dopamine, Electrochemical detection, Electrochemical sensors, Electroresponsive polymers, Films, Hydrogels, Pl, Plasma treatment, Release, Thermoelectric treatment, Thermoplastic polymers

Electrochemical sensors are sophisticated devices capable of detecting a wide range of chemical compounds with exceptional sensitivity and efficiency. Their importance is particularly pronounced in biomedical applications, where the rapid and accurate detection of biomolecules such as dopamine (DA), glucose (G), and nicotinamide adenine dinucleotide (NADH) is crucial for early diagnosis and disease management. These biomarkers are key in monitoring and managing conditions like diabetes, Parkinson and Alzheimer diseases, and bacterial infections. This review provides a comprehensive overview of electrochemical biosensors, detailing the methodologies commonly used by researchers and the latest technological advancements that enable more efficient device development. In this regard, the focus is on the impact and trends of various materials utilized in the fabrication of electrochemical biosensors, including conducting polymers, ceramics, and carbon-based materials. By examining the state of the art, we explore how these materials contribute to enhanced performance and reliability. Furthermore, while the development of highly selective and sensitive nanocomposites has been a primary focus in the field, this review also highlights efforts toward creating cost-effective biosensors with rapid prototyping capabilities. Such innovations aim to maintain high efficacy in electrochemical detection while making advanced diagnostics more accessible. In conclusion, this study aims to inform researchers and professionals about the evolving materials landscape in electrochemical biosensing, offering insights into the future directions of this critical technology.

JTD Keywords: Biomolecules, Biosensor, Dopamine, Electroactive materials, Electrochemical sensors, Electrode, Glucose biosensor, Nanoparticles, Nanosheets, Oxidas, Sensor, Temperature, Transition-metal carbides, Uric-acid

Chimeric antigen receptor (CAR)-T cells have made significant advancements in the field of adoptive immune cell therapies and the treatment of hematological malignancies. However, there are several drawbacks associated with the production and administration of these therapies. As a result, there has been interest in using natural killer (NK) cells to develop allogeneic CAR-NK cell therapies instead. While viral transduction is powerful for engineering T cells, NK cells have shown limited efficacy and high toxicity with this method. Therefore, efforts are being made to optimize non-viral transfection technologies for engineering NK cells. One such emerging technology is photoporation, which has demonstrated high efficiency and versatility for transfecting different immune cells. In this study, we evaluated the potential of nanoparticle-sensitized photoporation for genetic engineering of NK cells. Our findings show that both FD500 and eGFP mRNA can be successfully delivered into NK-92MI cells with high efficiency and low toxicity. When compared to state-of-the-art electroporation, photoporation proved to be more efficient, gentle, and capable of preserving the phenotype of NK-92MI cells. Overall, our work highlights the promising prospects of photoporation for NK cell engineering.

JTD Keywords: Cancer immunotherapie, Car, Cell engineering, Deliver, Messenger-rna, Nanoparticles, Natural killer cells, Natural-killer-cells, Photoporation, Polydopamine nanoparticles, T-cells

Surgical sutures are long-established medical devices that play an important role closing and healing damaged tissues and organs postoperatively. However, current commercial sutures are not able to detect infections at the wound site, which are quite frequent after surgery. In this work, we present mechanically stable smart sutures for the real-time monitoring of bacterial growth and biofilm formation. For this purpose, a conducting polymer named poly(3,4-ethylenedioxythiophene) (PEDOT), which is able to detect bacteria metabolites, was implemented as a coating onto commercial biostable sutures. A protecting hydrogel layer with adhesive properties, which was made of polydopamine-polyacrylamide (PDA-PAM), was used to prevent the detachment of the sensing coating of PEDOT upon looping and knotting the suture. The protective hydrogel preserved not only the knot mechanical properties of the suture but also the electrochemical response of the PEDOT-coating and, therefore, its ability to detect NADH from bacteria respiration. Ex-vivo assays using sutured swine intestine samples demonstrated that the suture with the PDA-PAM hydrogel layer detects the growth of bacteria in real tissues. As a proof of concept, sutures coated with PEDOT and protected with PDA-PAM were used to inhibit the local growth of bacteria in sutured intestines by applying controlled electrostimuli. Results evidenced that smart electro-responsive sutures can be used as multi-task devices focused on fighting bacterial infections, meaning not only monitoring but also hampering bacteria growth.

JTD Keywords: 4-ethylenedioxythiophene), Bacteria growth detection, Bacteria growth inhibition, Multi-task biomedical devices, Nanoparticles, Pape, Poly(3, Polydopamine-polyacrylamide, Sensor, Smart suture

Polypropylene (PP), thermoplastic polyurethane (TPU), polyethylene terephthalate glycol (PETG) and polylactic acid (PLA) 3D printed specimens, which are intrinsically non-electroresponsive materials, have been converted into electroresponsive electrodes applying a low-pressure oxygen plasma treatment. After complete chemical, morphological and electrochemical characterization, plasma treated samples have been applied as integrated electrochemical sensors for detecting dopamine and serotonin by cyclic voltammetry and chronoamperometry. Results show differences in the sensing behavior, which have been explained on the basis of the chemical structure of the pristine materials. While plasma treated PLA exhibits the highest performance as electrochemical sensor in terms of sensitivity (lowest limits of detection and quantification) and selectivity (against uric acid and ascorbic acid as interfering substances), plasma treated PP displays the poorest behavior due to its low polarity compared to PLA 3D-printed electrodes. Instead, plasma treated TPU and PETG shows a very good response, much closer to PLA, as sensitive electrodes towards neurotransmitter molecules (dopamine and serotonin). Overall, results open a new door for the fabrication of electrochemical conductive sensors using intrinsically insulating materials, without the need of chemical functionalization processes.

JTD Keywords: 3d printing, Amines, Ascorbic acid, Chemical characterization, Cyclic voltammetry, Dopamine, Electrochemical characterizations, Electrochemical sensor s, Electrochemical sensors, Electrode materials, Electroresponsive materials, Low-pressure oxygen-plasma treatments, Morphological characterization, Multiwalled carbon nanotubes (mwcn), Neurophysiology, Oxygen, Oxygen plasmas, Plastic bottles, Polyethylene terephthalate glycol, Polyethylene terephthalate glycols, Polyethylene terephthalates, Polylact i c acid, Polylactic acid, Polylactic acid pla, Polyols, Polypropylene, Polypropylene oxides, Polypropylenes, Polyurethanes, Reinforced plastics, Supercapacitors, Thermoplast i c polyurethane, Thermoplastic polyurethane, Thermoplastic polyurethanes

Very recently, the controlled release of dopamine (DA), a neurotransmitter whose deficiency is associated with Parkinson's disease, has been postulated as a good alternative to the oral administration of levodopa (L-Dopa), a dopamine precursor, to combat the effects of said disease. However, this is still a very little explored field and there are very few carriers that are capable of releasing DA, a small and water-soluble molecule, in an efficient and controlled manner. In this work, we report a carrier based on a conductive hydrogel capable of loading DA and releasing it progressively and efficiently (100 % release) in a period of five days by applying small electrical stimuli (-0.4 V) daily for a short time (1 min). The hydrogel (CMC/PEDOT), which is electrically active, has been prepared from sodium carboxymethylcellulose and poly(3,4-ethylenedioxythiophene) microparticles, using citric acid as a cross-linking agent. Furthermore, the results have shown that when relatively hydrophobic small molecules, such as chloramphenicol, are loaded, the electrostimulated release is significantly less efficient, demonstrating the usefulness of CMC/PEDOT as a carrier for neurotransmitters.

JTD Keywords: Amines, Carboxymethyl cellulose, Carboxymethylcellulose, Conducting hydrogels, Conducting polymers, Controlled release, Crosslinking, Dopamine, Drug-delivery system, Electrostimulation, Hydrogels, Joining, Levodopa, Loading, Molecules, Neurophysiology, Neurotransmitter release, Neurotransmitters release, Oral administration, Parkinson's disease, Parkinsons-disease, Poly(3,4-ethylenedioxythiophene), Release, Sodium, Transport, Water-soluble molecule

Neurotrophic factors are essential not only for guiding the organization of the developing nervous system but also for supporting the survival and growth of neurons after traumatic injury. In the central nervous system (CNS), inhibitory factors and the formation of a glial scar after injury hinder the functional recovery of neurons, requiring exogenous therapies to promote regeneration. Netrin-1, a neurotrophic factor, can initiate axon guidance, outgrowth, and branching, as well as synaptogenesis, through activation of deleted in colorectal cancer (DCC) receptors. We report here the development of a nanofiber-shaped supramolecular mimetic of netrin-1 with monomers that incorporate a cyclic peptide sequence as the bioactive component. The mimetic structure was found to activate the DCC receptor in primary cortical neurons using low molar ratios of the bioactive comonomer. The supramolecular nanofibers enhanced neurite outgrowth and upregulated maturation as well as pre- and postsynaptic markers over time, resulting in differences in electrical activity similar to neurons treated with the recombinant netrin-1 protein. The results suggest the possibility of using the supramolecular structure as a therapeutic to promote regenerative bioactivity in CNS injuries.

JTD Keywords: axon growth, axon guidance, cell-migration, colorectal-cancer, dcc, dopaminergic-neurons, force-field, functional recovery, netrin-1, neurite outgrowth, neuronal maturation, neurotrophic factor, neurotrophicfactor mimetic, synapsis, Axon growth, Axons, Cells, cultured, Central nervous system, Coarse-grained model, Nanofibers, Netrin-1, Neurogenesis, Neuronal maturation, Neurons, Neurotrophic factor mimetic, Peptide amphiphile, Synapsis

JTD Keywords: biocompatibility, blends, design, dopamine detection, electrocatalytic oxidation, electrodes, polymers, sensor, Additive manufacturing, Surface

When danger is perceived, the human body responds to overcome obstacles and survive a stressful situation; however, sustained levels of stress are associated with health disorders and diminished life quality. Hence, stress biomarkers are monitored to control stress quantitatively. Herein, a porous sensor (4l-COP/p) composed of poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(3,4-ethylenedioxythiophene-co-N-methylpyrrole) (COP), which is prepared in a four-layered fashion to detect dopamine (DA) and serotonin (5-HT), is presented. Specifically, the detection is conducted in phosphate-buffered saline (PBS), as well as artificial urine and sweat, by applying cyclic voltammetry. The limit of detection values obtained are as low as 5.7 x 10(-6) and 1.4 x 10(-6) m for DA and 5-HT, respectively, when assessed individually in artificial urine. When mixed in PBS, 4l-COP/p detects both biomarkers with a resolution of 0.18 V and a sensitivity of 40 and 30 mu A mm(-1) for DA and 5-HT, respectively. Additionally, by theoretical calculations, the interaction pattern that each stress biomarker establishes with the PEDOT outer layer is elucidated. Whereas DA interacts with the pi-system of PEDOT, 5-HT forms specific hydrogen bonds with the conducting polymer chains. The resolution value obtained depends upon such interactions. Overall, 4l-COP/p electrodes display potential as stress sensing devices for healthcare technologies.

JTD Keywords: Artificial body fluids, Boron-doped diamond, Cortisol, Cyclic voltammetry, Dopamine, Multilayered films, Paper, Saliva, Selective detection, Sensor, Sensors, Serotonin, Serum

Electrochemical sensors for real-time detection of several bioanalytes have been prepared by additive manufacturing, shaping non-conductive poly(lactic acid) (PLA) filaments, and applying a physical treatment to create excited species. The latter process, which consists of the application of power discharge of 100 W during 2 min in a chamber at a low pressure of O-2, converts electrochemically inert PLA into an electrochemically responsive material. The electric discharge caused the oxidation of the PLA surface as evidenced by the increment in the quantity of oxygenated species detected by FTIR spectroscopy and X-ray photoelectron spectroscopy (XPS). Indeed, changes in the surface chemical composition became more pronounced with increasing O-2 pressure. After demonstrating the performance of the chemically modified material as individual dopamine and glucose sensors, multiplexed detection has been achieved by measuring simultaneously the two voltammetric signals. This has been performed by collecting the signals in two different regions, a naked chemically modified PLA for dopamine detection and a chemically modified PLA region functionalized with Glucose Oxidase. These outcomes led to define a new paradigm for manufacturing electrodes for electrochemical sensors based on 3D printing without using conducting materials at any stage of the process.

JTD Keywords: Additive manu f a c turing, Carbon, Conductivity, Degradation, Dopamine, Dopamine detection, Glucose detection, Glucose sensors, Immobilization, Multiplexed detect i o n, Oxidase, Plasma treatment

Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions, and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here, we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a timescale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illumination-dependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wild-type animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes.

JTD Keywords: azobenzene, behavior, brainwave, d-1, dopamine, gpcr, in vivo electrophysiology, inhibitors, optogenetics, optopharmacology, photochromism, photopharmacology, photoswitch, stimulation, zebrafish, Animals, Animals, wild, Azobenzene, Behavior, Brainwave, Dopamine, Gpcr, In vivo electrophysiology, Ligands, Mice, Optogenetics, Optopharmacology, Photochromism, Photopharmacology, Photoswitch, Receptors, Synaptic transmission, Zebrafish

Bacteria biohybrids employ the motility and power of swimming bacteria to carry and maneuver microscale particles. They have the potential to perform microdrug and cargo delivery in vivo, but have been limited by poor design, reduced swimming capabilities, and impeded functionality. To address these challenge, motile Escherichia coli are captured inside electropolymerized microtubes, exhibiting the first report of a bacteria microswimmer that does not utilize a spherical particle chassis. Single bacterium becomes partially trapped within the tube and becomes a bioengine to push the microtube though biological media. Microtubes are modified with "smart" material properties for motion control, including a bacteria-attractant polydopamine inner layer, addition of magnetic components for external guidance, and a biochemical kill trigger to cease bacterium swimming on demand. Swimming dynamics of the bacteria biohybrid are quantified by comparing "length of protrusion" of bacteria from the microtubes with respect to changes in angular autocorrelation and swimmer mean squared displacement. The multifunctional microtubular swimmers present a new generation of biocompatible micromotors toward future microbiorobots and minimally invasive medical applications.

JTD Keywords: Biohybrids, E. coli, Micromotors, Microswimmers, Polydopamine