Publications

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

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

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

Polymeric membranes exhibit unique and modulate transport properties when they are properly functionalised, which make them ideal for ions transport, molecules separation and molecules interactions. The present work proposes the design and fabrication of nanostructured membranes, composed by biodegradable poly(lactic acid) (PLA) and poly(ethylene glycol) (PEG), incorporating a lipophilic molecule (cholesterol) covalently bonded, were especially designed to provide even more application opportunities in sensors field. Electrochemical studies, by means of electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave voltammetry (SWV), revealed important differences regarding the functionalised and non-functionalised PLA systems. PEGcholesterol building block units showed a clear affinity with ascorbic acid (vitamin C) and Trolox (R) (a watersoluble analogue of vitamin E), both hydrophilic in nature, with a limit of detection capacity of 8.12 mu M for AA and 3.53 mu M for AA and Trolox, respectively, in aqueous salt solution. The bioinspired polymer may be used to incorporate antioxidant property that allow the design of anti-stress biosensors, electrodes for the detection of vitamin C or vitamin E in biomedical nutrition programs, among other applications.

JTD Keywords: Antioxidant molecules, Antioxidants, Application programs, Ascorbic acid, Biomimetics, C (programming language), Capacity, Chemical detection, Cholesterol, Cyclic voltammetry, Electrochemical detection, Electrochemical impedance spectroscopy, Functional polymers, Functionalized, Lactic acid, Molecules, Nanomembranes, Poly ethylene glycols, Poly lactic acid, Poly(ethylene glycol), Poly(ethyleneglycol), Poly(lactic acid), Polyethylene glycols, Vitamin-e

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

Mimicking bone extracellular matrix (ECM) is paramount to develop novel biomaterials for bone tissue engineering. In this regard, the combination of integrin-binding ligands together with osteogenic peptides represents a powerful approach to recapitulate the healing microenvironment of bone. In the present work, we designed polyethylene glycol (PEG)-based hydrogels functionalized with cell instructive multifunctional biomimetic peptides (either with cyclic RGD-DWIVA or cyclic RGD-cyclic DWIVA) and cross-linked with matrix metalloproteinases (MMPs)-degradable sequences to enable dynamic enzymatic biodegradation and cell spreading and differentiation. The analysis of the intrinsic properties of the hydrogel revealed relevant mechanical properties, porosity, swelling and degradability to engineer hydrogels for bone tissue engineering. Moreover, the engineered hydrogels were able to promote human mesenchymal stem cells (MSCs) spreading and significantly improve their osteogenic differentiation. Thus, these novel hydrogels could be a promising candidate for applications in bone tissue engineering, such as acellular systems to be implanted and regenerate bone or in stem cells therapy.Copyright © 2023 Oliver-Cervelló, Martin-Gómez, Gonzalez-Garcia, Salmeron-Sanchez, Ginebra and Mas-Moruno.

JTD Keywords: biomaterials, cross-linking, dwiva, functionalization, hydrogel, integrin, kinetics, marrow stromal cells, matrices, multifunctionality, myogenic differentiation, osteogenic differentiation, regeneration, stem-cells, Biomimetic peptides, Dwiva, Functionalization, Hydrogel, Multifunctionality, Osteogenic differentiation, Poly(ethylene glycol) hydrogels

Virtually, all implantable medical devices are susceptible to infection. As the main healthcare issue concerning implantable devices is the elevated risk of infection, different strategies based on the coating or functionalization of biomedical devices with antiseptic agents or antibiotics are proposed. In this work, an alternative approach is presented, which consists of the functionalization of implantable medical devices with sensors capable of detecting infection at very early stages through continuous monitoring of the bacteria metabolism. This approach, which is implemented in surgical sutures as a representative case of implantable devices susceptible to bacteria colonization, is expected to minimize the risk of worsening the patient's clinical condition. More specifically, non-absorbable polypropylene/polyethylene (PP/PE) surgical sutures are functionalized with conducting polymers using a combination of low-pressure oxygen plasma, chemical oxidative polymerization, and anodic polymerization, to detect metabolites coming from bacteria respiration. Functionalized suture yarns are used for real-time monitoring of bacteria growth, demonstrating the potential of this strategy to fight against infections.© 2023 Wiley-VCH GmbH.

JTD Keywords: adhesion, biofilm, conducting polymers, contamination, derivatives, detections, functionalized sutures, nadh, poly(3,4-ethylenedioxythiophene), Bacteria growth, Conducting polymers, Detections, Functionalized sutures, Monofilament, Nadh

JTD Keywords: 4-ethylenedioxythiophene), carbon nanoparticles, conductive hydrogel, manganese oxide poly(3, sensors, supercapacitor, supercapacitors, temperature sensor, Alginate, Carbon nanotubes

In addition of a key catecholamine neurotransmitter, dopamine is is the metabolite predominantly produced by specific types of tumors (e.g. paragangliomas and neuroblastomas), which cannot be diagnosed using conven-tional sensitive tests. Within this context, development of flexible electrochemical sensors to monitor dopamine levels in physiological fluids for the early diagnosis and control of diseases related to abnormal levels of such compound, is necessary. In this work, a flexible self-supported membrane, which acts directly as electrode, has been developed to detect dopamine. The membrane consists of three nanoperforated polylactic acid (PLA) layers, which provide flexibility and mechanical integrity, separated by two layers of an electroactive copolymer, which are obtained by electrochemical copolymerization of 3,4-ethylenedioxythiophene and aniline. The sensitivity and detection limit provided by the electroactive copolymer, which is accessible to dopamine molecules through the nanoperforations of the PLA outer layers, is 1.846 mu A/(cm2.mu M) and 1.7 mu M, respectively, in a urea-rich environments that mimics urine. These values allow us to propose the self-standing flexible electrodes devel-oped in this study for the detection of dopamine in patients affected by paragangliomas and neuroblastomas tumors, which typically present dopamine concentrations between 2 and 7 mu M.

JTD Keywords: 4-ethylenedioxythiophene), Conducting polymer, Electrochemical sensor, Electrodes, Hydrogels, Poly(3, Polyaniline, Polylactic acid, Selective detection, Sensors, Supercapacitors

Innovative insulin delivery systems contemplate combining multi-pharmacokinetic profiles for glycemic control. Two device configurations have been designed for the controlled release of insulin using the same chemical compounds. The first insulin delivery system, which displays a rapid release response that, in addition, is enhanced on a short time scale by electrical stimulation, consists on an insulin layer sandwiched between a conducting poly(3,4-ethylenedioxythiophene) (PEDOT) film and a poly-gamma-glutamic acid (gamma-PGA) hydrogel. The second system is constituted by gamma-PGA hydrogel loaded with insulin and PEDOT nanoparticles by in situ gelation. In this case, the insulin release, which only starts after the degradation of the hydrogel over time (i.e. on a long time scale), is slow and sustained. The combination of an on-demand and fast release profile with a sustained and slow profile, which act on different time scales, would result in a very efficient regulation of diabetes therapy in comparison to current systems, allowing to control both fast and sustained glycemic events. Considering that the two systems developed in this work are based on the same chemical components, future work will be focused on the combination of the two kinetic profiles by re-engineering a unique insulin release device using gamma-PGA, PEDOT and insulin.

JTD Keywords: Conducting polymer, Constant, Diabetes, Diabetes-mellitus, Drug-delivery, Electrodes, Electrostimulation, Glucose-responsive hydrogels, Hydrogel, Molecular dynamics, Molecular-dynamics, Nanogels, Nanoparticles, Poly(3,4-ethylenedioxythiophene), Risk

JTD Keywords: anti-fxiia antibody, artificial surfaces, blood compatibility, complement activation, factor xii, fibrinolytic system, hemocompatible coatings, interactive hemocompatibility, poly(2-methacryloyloxyethyl phosphorylcholine), polyethylene oxide, polymer brushes, radical polymerization, sequential coimmobilization, Antifouling polymer brushes, Protein adsorption

A hydrogel/nanoparticle-loaded system for the controlled delivery of small hydrophobic drugs has been prepared using poly(gamma-glutamic acid) (PGGA), a naturally occurring biopolymer made of glutamic acid units connected by amide linkages between alpha-amino and gamma-carboxylic acid groups, and poly(3,4-ethylenedioxythiophene) (PEDOT), a very stable conducting polymer with excellent electrochemical response. Specifically, curcumin (CUR)-loaded PEDOT nanoparticles (PEDOT/CUR) were incorporated to the PGGA hydrogel during the crosslinking reaction. After chemical, morphological and electrochemical characterization, the release profiles of PEDOT/CUR and PGGA/PEDOT/CUR system have been compared in absence and presence of electrical stimuli, which consisted on the application of a voltage of -0.5 V for 15 min every 24 h. Results show that the release is higher for electrically stimulated systems by more than twice, even though due to its hydrophobicity and poor solubility in water the release was relatively slow in both cases. This feature could be advantageous when the therapeutic treatment requires slow, controlled and sustained CUR release.

JTD Keywords: 4-ethylenedioxythiophene), Acid, Controlled-release, Curcumi n, Curcumin, Electrostimulated release, Nanocarriers, Pedotpss, Poly( ?-glutamic acid), Poly(3

Tuning of the crosslink density (CLD) in the rubber compounds is very crucial for optimizing the physical and mechanical properties of the ultimate rubber products. Conventionally, CLD can be measured via rheological methods such as moving die rheometer (MDR), via mechanical tests such as temperature scanning stress relaxation analysis (TSSR), or via direct swelling experiments using Flory–Rehner approach. In the current study, two novel techniques, focused ion beam - scanning electron microscopy (FIB-SEM) processing, with simultaneous energy dispersive X-ray spectrometry (EDS) mapping analysis and scanning acoustic microscopy (SAM) were combined and correlated to conventional methods on a model recipe of ethylene propylene diene monomer (EPDM) compound having different sulphur contents. Depending on the applied technique, the increase in the crosslink density with sulphur content was found to be 1.7 fold for the Flory–Rehner approach and 1.2 fold for both TSSR and MDR. It is directly monitored from the FIB-SEM-EDS analysis that the sulphur distribution and agglomeration behavior increased in line with ZnO content, which is an indirect indication of the rise in crosslink density. The impedance maps of the crosslinked samples obtained through SAM analysis revealed that the impedance of the samples increased with the increasing sulphur content, which can be attributed to higher level of crosslink density. A quantified correlation was obtained between SAM images and the crosslink density of the samples. It was shown that SAM is a promising tool for practical and non-destructive analysis for determining the formation of crosslink density of the rubbers. © The Author(s) 2022.

JTD Keywords: blends, compressibility, crosslink density, cure characteristics, ethylene propylene diene monomer, focused ion beam, mechanical-properties, morphology, natural-rubber, particles, scanning acoustic microscopy, scanning electron microscopy, sulfur, thermal-stability, vulcanization, Composite soft materials, Cross-link densities, Crosslink density, Crosslinking, Density (specific gravity), Ethylene, Ethylene propylene diene monomer, Flory-rehner, Focused ion beam - scanning electron microscopy, Focused ion beam-scanning electron microscopies, Ii-vi semiconductors, Monomers, Moving die rheometers, Physical and mechanical properties, Propylene, Relaxation analysis, Rubber, Scanning acoustic microscopy, Scanning electron microscopy, Stress relaxation, Sulfur contents, Temperature scanning stress relaxations, Zinc oxide

Polypeptide-based nanoparticles offer unique advantages from a nanomedicine perspective such as biocompatibility, biodegradability, and stimuli-responsive properties to (patho)physiological conditions. Conventionally, self-assembled polypeptide nanostructures are prepared by first synthesizing their constituent amphiphilic polypeptides followed by postpolymerization self-assembly. Herein, we describe the one-pot synthesis of oxidation-sensitive supramolecular micelles and vesicles. This was achieved by polymerization-induced self-assembly (PISA) of the N-carboxyanhydride (NCA) precursor of methionine using poly(ethylene oxide) as a stabilizing and hydrophilic block in dimethyl sulfoxide (DMSO). By adjusting the hydrophobic block length and concentration, we obtained a range of morphologies from spherical to wormlike micelles, to vesicles. Remarkably, the secondary structure of polypeptides greatly influenced the final morphology of the assemblies. Surprisingly, wormlike micellar morphologies were obtained for a wide range of methionine block lengths and solid contents, with spherical micelles restricted to very short hydrophobic lengths. Wormlike micelles further assembled into oxidation-sensitive, self-standing gels in the reaction pot. Both vesicles and wormlike micelles obtained using this method demonstrated to degrade under controlled oxidant conditions, which would expand their biomedical applications such as in sustained drug release or as cellular scaffolds in tissue engineering.

JTD Keywords: alpha-amino-acid, hydrogels, leuchs anhydrides, platform, polypeptides, transformation, triggered cargo release, Amino acids, Amphiphilics, Biocompatibility, Biodegradability, Block lengths, Controlled drug delivery, Dimethyl sulfoxide, Ethylene, Gels, Hydrophobicity, Medical nanotechnology, Methionine, Micelles, Morphology, One-pot synthesis, Organic solvents, Oxidation, Physiological condition, Polyethylene oxides, Post-polymerization, Ring-opening polymerization, Scaffolds (biology), Self assembly, Stimuli-responsive properties, Supramolecular chemistry, Supramolecular gels, Supramolecular micelles, Wormlike micelle

The importance of PEG architecture on nanoparticle (NP) functionality is known but still difficult to investigate, especially at a single particle level. Here, we apply DNA Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT), a super-resolution microscopy (SRM) technique, to study the surface functionality in poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) NPs with different PEG structures. We demonstrated how the length of the PEG spacer can influence the accessibility of surface chemical functionality, highlighting the importance of SRM techniques to support the rational design of functionalized NPs.

JTD Keywords: chain-length, density, plga, surface, systems, Chain-length, Density, Dna, Microscopy technique, Nanoparticles, Nanoscale topography, Paint, Peg spacers, Plga, Poly lactide-co-glycolide, Poly-lactide-co-glycolide, Polyethylene glycols, Polylactide-co-glycolide, Single-particle, Super-resolution microscopy, Superresolution microscopy, Surface, Surface chemicals, Surface functionalities, Systems

Rapid detection of bacterial presence on implantable medical devices is essential to prevent biofilm formation, which consists of densely packed bacteria colonies able to withstand antibiotic-mediated killing. In this work, a smart approach is presented to integrate electrochemical sensors for detecting bacterial infections in biomedical implants made of isotactic polypropylene (i-PP) using chemical assembly. The electrochemical detection is based on the capacity of conducting polymers (CPs) to detect extracellular nicotinamide adenine dinucleotide (NADH) released from cellular respiration of bacteria, which allows distinguishing prokaryotic from eukaryotic cells. Oxygen plasma-functionalized free-standing i-PP, coated with a layer (≈1.1 µm in thickness) of CP nanoparticles obtained by oxidative polymerization, is used as working electrode for the anodic polymerization of a second CP layer (≈8.2 µm in thickness), which provides very high electrochemical activity and stability. The resulting layered material, i-PP /CP , detects the electro-oxidation of NADH in physiological media with a sensitivity 417 µA cm and a detection limit up to 0.14 × 10 m, which is below the concentration of extracellular NADH found for bacterial cultures of biofilm-positive and biofilm-negative strains. f 2 −2 −3

JTD Keywords: bacteria respiration, bacteria sensors, biomedical implants, flexible sensors, poly(3,4-ethylenedioxythiophene), Bacteria respiration, Bacteria sensors, Biomedical implants, Flexible sensors, Poly(3,4-ethylenedioxythiophene)

A new methodology for the pH-triggered degradation of polymers or for the release of drugs under visible light irradiation based on the cyclization of ortho-hydroxy-cinnamates (oHC) to coumarins is described. The key oHC structural motif can be readily incorporated into the rational design of novel photocleavable polymers via click chemistry. This main-chain moiety undergoes a fast photocleavage when irradiated with 455 nm light provided that a suitable base is added. A series of polyethylene glycol-alt-ortho-hydroxy cinnamate (polyethylene glycol (PEG)(n)-alt-oHC)-based polymers are synthesized and the time-dependent visible-light initiated cleavage of the photoactive monomer and polymer is investigated in solution by a variety of spectroscopic and chromatographic techniques. The photo-degradation behavior of the water-soluble poly(PEG(2000)-alt-oHC) is investigated within a broad pH range (pH = 2.1-11.8), demonstrating fast degradation at pH 11.8, while the stability of the polymer is greatly enhanced at pH 2.1. Moreover, the neat polymer shows long-term stability under daylight conditions, thus allowing its storage without special precautions. In addition, two water-soluble PEG-based drug-carrier molecules (mPEG(2000)-oHC-benzhydrol/phenol) are synthesized and used for drug delivery studies, monitoring the process by UV-vis spectroscopy in an ON/OFF intermittent manner.

JTD Keywords: coumarins, drug delivery, e/z-double bond isomerization, o-hydroxy cinnamates, polymer degradation, Aliphatic compounds, Antioxidant activity, Antitumor, Chromatographic techniques, Chromatography, Cis/trans isomerization, Controlled drug delivery, Coumarin derivatives, Coumarins, Drug delivery, Drug delivery system, E/z-double bond isomerization, Films, Hydrogels, Image enhancement, Light, Long term stability, O-hydroxy cinnamates, Particles, Photoactive monomers, Photodegradation, Polyethylene glycols, Polyethylenes, Polymer degradation, Responsive polymers, Salts, Structural motifs, Synthesis (chemical), Targeted drug delivery, Visible light photocatalysis, Visible-light irradiation

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

© 2020 Elsevier B.V. Semi-interpenetrated nanogels (NGs) able to release and sense diclofenac (DIC) have been designed to act as photothermal agents with the possibility to ablate cancer cells using mild-temperatures (<45 °C). Combining mild heat treatments with simultaneous chemotherapy appears as a very promising therapeutic strategy to avoid heat resistance or damaging the surrounding tissues. Particularly, NGs consisted on a poly(N-isopropylacrylamide) (PNIPAM) and dendritic polyglycerol (dPG) mesh containing a semi-interpenetrating network (SIPN) of poly(hydroxymethyl 3,4-ethylenedioxythiophene) (PHMeEDOT). The PHMeEDOT acted as photothermal and conducting agent, while PNIPAM-dPG NG provided thermoresponsivity and acted as stabilizer. We studied how semi-interpenetration modified the physicochemical characteristics of the thermoresponsive SIPN NGs and selected the best condition to generate a multifunctional photothermal agent. The thermoswitchable conductiveness of the multifunctional NGs and the redox activity of DIC could be utilized for its electrochemical detection. Besides, as proof of the therapeutic concept, we investigated the combinatorial effect of photothermal therapy (PTT) and DIC treatment using the HeLa cancer cell line in vitro. Within 15 min NIR irradiation without surpassing 45 °C we were able to kill 95% of the cells, demonstrating the potential of SIPN NGs as drug carriers, sensors and agents for mild PTT.

JTD Keywords: cells, cellulose, conducting polymers, controlled delivery, diclofenac, efficiency, electrochemical oxidation, electrochemical sensors, nanogels, nanoparticles, photothermal therapy, pnipam, poly(3,4-ethylenedioxythiophene), Conducting polymers, Electrochemical sensors, Nanogels, Photothermal therapy

Strategies to inhibit initial bacterial adhesion are extremely important to prevent infection on biomaterial surfaces. However, the simultaneous attraction of desired eukaryotic cells remains a challenge for successful biomaterial-host tissue integration. Here we describe a method for the development of a trifunctional coating that repels contaminating bacteria, kills those that adhere, and promotes osteoblast adhesion. To this end, titanium surfaces were functionalized by electrodeposition of an antifouling polyethylene glycol (PEG) layer and subsequent binding of a peptidic platform with cell-adhesive and bactericidal properties. The physicochemical characterization of the samples via SEM, contact angle, FTIR and XPS analysis verified the successful binding of the PEG layer and the biomolecules, without altering the morphology and topography of the samples. PEG coatings inhibited protein adsorption and osteoblast-like (SaOS-2) attachment; however, the presence of cell adhesive domains rescued osteoblast adhesion, yielding higher values of cell attachment and spreading compared to controls (p < 0.05). Finally, the antibacterial potential of the coating was measured by live/dead assays and SEM using S. sanguinis as a model of early colonizer in oral biofilms. The presence of PEG layers significantly reduced bacterial attachment on the surfaces (p < 0.05). This antibacterial potential was further increased by the bactericidal peptide, yielding values of bacterial adhesion below 0.2% (p < 0.05). The balance between the risk of infection and the optimal osteointegration of a biomaterial is often described as “the race for the surface”, in which contaminating bacteria and host tissue cells compete to colonize the implant. In the present work, we have developed a multifunctional coating for a titanium surface that promotes the attachment and spreading of osteoblasts, while very efficiently inhibits bacterial colonization, thus holding promise for application in bone replacing applications.

JTD Keywords: Polyethylene glycol, Antibacterial, Osteointegration, Multifunctionality, Peptides, Titanium

In this paper, we fabricate a flexible and location traceable micromotor, called organo-motor, assisted by microfluidic devices and with high throughput. The organo-motors are composed of organic hydrogel material, poly (ethylene glycol) diacrylate (PEGDA), which can provide the flexibility of their structure. For spatial and temporal traceability of the organo-motors under magnetic resonance imaging (MRI), superparamagnetic iron oxide nanoparticles (SPION; Fe3O4) were incorporated into the PEGDA microhydrogels. Furthermore, a thin layer of platinum (Pt) was deposited onto one side of the SPION-PEGDA microhydrogels providing geometrical asymmetry and catalytic propulsion in aqueous fluids containing hydrogen peroxide solution, H2O2. Furthermore, the motion of the organo-motor was controlled by a small external magnet enabled by the presence of SPION in the motor architecture.

JTD Keywords: Flexible, Hydrogel, Magnetic resonance imaging, Microfluidics, Micromotor, Microparticle, Organo-motor, Poly (ethylene glycol) diacrylate, Self-propulsion, Superparamagnetic iron oxide nanoparticles

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

Rapid and inexpensive development of electrochemical sensors with good exploitation potential may be produced using a polymer as a substrate material. However, fabrication of polymer-based sensors is challenging. Using photolithography and etching of gold-coated poly(ethylene-2,6-naphthalate) (PEN), we have succeeded in fabricating disk-shaped and interdigitated microelectrodes (uEs). The electrodes have an excellent adhesion to the polymer and are encapsulated using a novel room-temperature process, applicable for low-cost, high-throughput fabrication. The PEN surface has been characterized in respect of wettability, surface energy and surface roughness. Finally, the electrodes give stable and reproducible electrochemical impedance spectroscopy and cyclic voltammetry responses, using the redox couple ferrocyanide and ruthenium hexamine. The results demonstrate the robustness and functionality of the polymer-based sensor platform with minimum feature sizes of 6 um.

JTD Keywords: Poly(ethylene naphthalate), Photolithography, Microelectrodes, Interdigitated electrodes, Electrochemical characterization, Electrochemical sensor

In this study, polylactic acid (PLA) and polyethylene glycol (PEG) were combined with soluble CaP glass particles and processed by rapid prototyping to obtain fully biodegradable structures for Tissue Engineering applications. The obtained 3D biodegradable structures were characterized in terms of their architecture and mechanical properties. The scaffold morphology, internal micro-architecture and mechanical properties were evaluated using Scanning Electron Microscopy (SEM), micro-computed tomography (micro-CT) and mechanical testing, respectively. Well defined structures with pore size of 350-400μm (in the axial view), struts width of approximately 70-80μm, and a porosity ranging between 60-65% were obtained. The combination RP and PLA/PEG/CaP glass turned into promising fully degradable, mechanically stable, bioactive and biocompatible composite scaffolds for TE.

JTD Keywords: Axial view, Biodegradable composites, Composite scaffolds, Glass particles, Mechanically stable, Micro architectures, Micro computed tomography (micro-CT), Poly lactic acid, Scaffold morphology, Tissue engineering applications, Well-defined structures, Bioactive glass, Mechanical properties, Mechanical testing, Polyethylene glycols, Polymer blends, Rapid prototyping, Scaffolds (biology), Scanning electron microscopy, Computerized tomography

This article describes a simple method for the construction of a universal surface chemical gradient platform based on the biotin streptavidin model. In this approach, surface chemical gradients were prepared in poly(methyl methacrylate) (PM MA), a biocompatible polymer, by a controlled hydrolysis procedure. The physicochemical properties of the resulting modified surfaces were extensively characterized. Chemical analysis carried out via time-of-flight secondary ion mass spectrometry (ToRSIMS) and X-ray photoelectron spectroscopy (XPS) showed the formation of a smooth, highly controllable carboxylic acid gradient of increasing concentration along the sample surface. Atomic force microscopy (AFM) and contact angle (CA) results indicate that, in contrast with most of the chemical gradient methods published in the literature, the chemical modification of the polymer surface barely affects its physical properties. The introduction of carboxylic acid functionality along the surface was then used for biomolecule anchoring. For this purpose, the surface was activated and derivatized first with biotin and finally with streptavidin (SA V) in a directed orientation fashion. The SAV gradient was qualitatively assessed by fluorescence microscopy analysis and quantified by surface plasmon resonance (SPR) in order to establish a quantitative relationship between SAV surface densities and the surface location. The usefulness of the fabrication method described for biological applications was tested by immobilizing biotinylated bradykinin onto the SAV gradient. This proof-of-concept application shows the effectiveness of the concentration range of the gradient because the effects of bradykinin on cell morphology were observed to increase gradually with increasing drug concentrations. The intrinsic characteristics of the fabricated gradient platform (absence of physicochemical modifications other than those due to the biomolecules included) allow us to attribute cell behavior unequivocally to the biomolecule surface density changes.

JTD Keywords: Wettability gradient, Polyethylene surface, Combinatorial, Immobilization, Biomaterials, Fabrication, Deposition, Bradykinin, Monolayers, Discharge

Adhesion of tissue cells is a prerequisite for their growth and differentiation but prevents also apoptosis. Here the layer-by-layer technique (LbL) was used to design multilayer structures of poly(ethylene imine) (PEI) and heparin (HEP) on glass as model biomaterial to control the adhesion of primary human dermal fibroblasts. Distinct surface features like wettability, charge and lateral structures were controlled by changing the pH value of the HEP solution during multilayer assembly to acidic neutral or alkaline, values. While plain terminal layers were rather cytophobic, the pre-adsorption of serum or fibronectin (FN) caused a distinct change in cell morphology in dependence on the pH setup. The effect of serum was more prominent on PEI layers probably due to their positive surface charge, whereas the effect of FN was more pronounced on HEP terminated multilayers possibly due to its ability to bind FN specifically. Those layers which hampered cell adhesion also inhibited growth of human fibroblasts under serum conditions. Conversely, on layers where cell adhesion was increased also an elevated growth and, thus, metabolic activity was observed.

JTD Keywords: Surface modification, Layer-by-layer, Poly(ethylene imine), Heparin, Serum, Fibronectin

In today's store-houses the ripening of fruit is controlled by managing the ethylene concentration in the ambient atmosphere. Precise and continuous ethylene monitoring is very advantageous since low ethylene concentrations are produced by the fruit itself and are indicative of its ripeness, and on other occasions, ethylene is externally added when ripeness or degreening of the product must be promoted. In this work, a multichannel mid-infrared spectrometer for ethylene measurement is built and characterized. The instrument contains additional channels to reject potential cross-interferences like ammonia and ethanol. Additionally, these channels are useful for monitoring a potential malfunction of the cooling system and possible fouling of the fruit, respectively. The complete spectrometer contains a silicon-based macroporous infrared (IR) emitter, a miniaturized long path cell (white cell), a four-channel detector module, low-noise analog amplification and filtering, and a microcontroller-based lock-in amplifier. The new inner architecture of the detector module features a fourfold thermopile array with narrow band optical filters attached by flip-chip technology, and a Fresnel lens array attached on the lid of the package. Laboratory tests show that the system is able to distinguish between ammonia and ethylene, featuring a detection limit of 30 ppm and 160 ppm (95% confidence) for ethylene and ammonia, respectively. Field tests show that the spectrometer is suitable as an ethylene alarm to detect fruit ripening and prevent fruit to decline into senescence. Simulation results show that system selectivity could be improved by setting ammonia channel to another absorption wavelength.

JTD Keywords: IR spectrometer, Ethylene, Fruit storage, Fresnel lens, White cell, Lock-in amplifier

A fundamental aspect of the rapidly expanding medical care sector, bone repair continues to benefit from emerging technological developments. This text provides researchers and students with a comprehensive review of the materials science and engineering principles behind these developments. The first part reviews the fundamentals of bone repair and regeneration. Further chapters discuss the science and properties of biomaterials used in bone repair, including both metals and biocomposites. Final chapters analyze device considerations such as implant lifetime and failure, and discuss potential applications, as well as the ethical issues that continually confront researchers and clinicians.

JTD Keywords: Ultra high molecular weight polyethylene (UHMWPE), Acrylic polymers as bone cement, Biodegradable polymers