Bioinspired micro- and nano-structured neural interfaces.

The development of a functional nervous system requires neurons to interact with and promptly respond to a wealth of biochemical, mechanical and topographical cues found in the neural extracellular matrix (ECM). Among these, ECM topographical cues have been found to strongly influence neuronal function and behavior. Here, we discuss how the blueprint of the architectural organization of the brain ECM has been tremendously useful as a source of inspiration to design biomimetic substrates to enhance neural interfaces and dictate neuronal behavior at the cell-material interface. In particular, we focus on different strategies to recapitulate cell-ECM and cell-cell interactions. In order to mimic cell-ECM interactions, we introduce roughness as a first approach to provide informative topographical biomimetic cues to neurons. We then examine 3D scaffolds and hydrogels, as softer 3D platforms for neural interfaces. Moreover, we will discuss how anisotropic features such as grooves and fibers, recapitulating both ECM fibrils and axonal tracts, may provide recognizable paths and tracks that neuron can follow as they develop and establish functional connections. Finally, we show how isotropic topographical cues, recapitulating shapes, and geometries of filopodia- and mushroom-like dendritic spines, have been instrumental to better reproduce neuron-neuron interactions for applications in bioelectronics and neural repair strategies. The high complexity of the brain architecture makes the quest for the fabrication of create more biologically relevant biomimetic architectures in continuous and fast development. Here, we discuss how recent advancements in two-photon polymerization and remotely reconfigurable dynamic interfaces are paving the way towards to a new class of smart biointerfaces forin vitroapplications spanning from neural tissue engineering as well as neural repair strategies.

Fundamentals of Skin Bioimpedances.

The bioimpedances of tissues beyond the stratum corneum, which is the outermost layer of skin, contain crucial clinical information. Nevertheless, bioimpedance measurements of both the viable skin and the adipose tissue are not widely used, mainly because of the complex multilayered skin structure and the electrically insulating nature of the stratum corneum. Here, a theoretical framework is established for analyzing the impedances of multilayered tissues and, in particular, of skin. Then, strategies are determined for the system-level design of electrodes and electronics, which minimize 4-wire (or tetrapolar) measurement errors even in the presence of a top insulating tissue, thus enabling non-invasive characterizations of tissues beyond the stratum corneum. As an example, non-invasive measurements of bioimpedances of living tissues are demonstrated in the presence of parasitic impedances which are much (e.g., up to 350 times) higher than the bioimpedances of the living tissues beyond the stratum corneum, independently on extreme variations of the barrier (tape stripping) or of the skin-electrode contact impedances (sweat). The results can advance the development of bioimpedance systems for the characterization of viable skin and adipose tissues in several applications, including transdermal drug delivery and the assessment of skin cancer, obesity, dehydration, type 2 diabetes mellitus, cardiovascular risk, and multipotent adult stem cells.

Azobenzene-based optoelectronic transistors for neurohybrid building blocks.

Exploiting the light-matter interplay to realize advanced light responsive multimodal platforms is an emerging strategy to engineer bioinspired systems such as optoelectronic synaptic devices. However, existing neuroinspired optoelectronic devices rely on complex processing of hybrid materials which often do not exhibit the required features for biological interfacing such as biocompatibility and low Young's modulus. Recently, organic photoelectrochemical transistors (OPECTs) have paved the way towards multimodal devices that can better couple to biological systems benefiting from the characteristics of conjugated polymers. Neurohybrid OPECTs can be designed to optimally interface neuronal systems while resembling typical plasticity-driven processes to create more sophisticated integrated architectures between neuron and neuromorphic ends. Here, an innovative photo-switchable PEDOT:PSS was synthesized and successfully integrated into an OPECT. The OPECT device uses an azobenzene-based organic neuro-hybrid building block to mimic the retina's structure exhibiting the capability to emulate visual pathways. Moreover, dually operating the device with opto- and electrical functions, a light-dependent conditioning and extinction processes were achieved faithful mimicking synaptic neural functions such as short- and long-term plasticity.

Twin-Wire Networks for Zero Interconnect, High-Density 4-Wire Electrical Characterizations of Materials.

Four-wire measurements have been introduced by Lord Kelvin in 1861 and have since become the standard technique for characterizing small resistances and impedances. However, high-density 4-wire measurements are generally complex, time-consuming, and inefficient because of constraints on interconnects, pads, external wires, and mechanical contacts, thus reducing reproducibility, statistical significance, and throughput. Here, we introduce, systematically design, analyze, and experimentally validate zero interconnect networks interfaced to external instrumentation by couples of twin wire. 3D-printed holders with magnets, interconnects, nonadhesive layers, and spacers can effortlessly establish excellent electrical connections with tunable or minimum contact forces and enable accurate measurements even for delicate devices, such as thin metals on soft polymers. As an example, we measured all the resistances of a twin-wire 29-resistor network made of silver-nanoparticle ink printed on polyimide, paper, or photo paper, including during sintering or temperature calibration, resulting in an unprecedentedly easy and accurate characterization of both resistivity and its temperature coefficient. The theoretical framework and experimental strategies reported here represent a breakthrough toward zero interconnect, simple, and efficient high-density 4-wire characterizations, can be generalized to other 4-wire measurements (impedances, sensors) and can open the way to more statistically meaningful and reproducible analyses of materials, high-throughput measurements, and minimally invasive characterizations of biomaterials.

Two-photon polymerization lithography enabling the fabrication of PEDOT:PSS 3D structures for bioelectronic applications.

Conductive 3D platforms have gained increasing attention in bioelectronics thanks to the improvement in the cell-chip coupling. PEDOT:PSS is nowadays widely employed in bioelectronic applications thanks to its electrical and mechanical properties. In this work, an innovative fabrication method for the realization of PEDOT:PSS-based conductive micropillars and 3D cage-like structures is presented, combining two-photon lithography and electrodeposition techniques.

Double-Framed Thin Elastomer Devices.

Elastomers and, in particular, polydimethylsiloxane (PDMS) are widely adopted as biocompatible mechanically compliant substrates for soft and flexible micro-nanosystems in medicine, biology, and engineering. However, several applications require such low thicknesses (e.g., <100 µm) that make peeling-off critical because very thin elastomers become delicate and tend to exhibit strong adhesion with carriers. Moreover, microfabrication techniques such as photolithography use solvents which swell PDMS, introducing complexity and possible contamination, thus limiting industrial scalability and preventing many biomedical applications. Here, we combine low-adhesion and rectangular carrier substrates, adhesive Kapton frames, micromilling-defined shadow masks, and adhesive-neutralizing paper frames for enabling fast, easy, green, contaminant-free, and scalable manufacturing of thin elastomer devices, with both simplified peeling and handling. The accurate alignment between the frame and shadow masks can be further facilitated by micromilled marking lines on the back side of the low-adhesion carrier. As a proof of concept, we show epidermal sensors on a 50 µm-thick PDMS substrate for measuring strain, the skin bioimpedance and the heart rate. The proposed approach paves the way to a straightforward, green, and scalable fabrication of contaminant-free thin devices on elastomers for a wide variety of applications.

Luminescent cis-Iridium(III) Complex Based on a Bis(6,7-dimethoxy-3,4-dihydroisoquinoline) Platform Featuring an Unusual cis Orientation of the C∧N Ligands: From a Theoretical Approach to a Deep Red LEEC Device.

By pursuing the strategy of manipulating natural compounds to obtain functional materials, in this work, we report on the synthesis and characterization of a luminescent cationic iridium complex (cis-1), designed starting from the catecholic neurotransmitter dopamine, exhibiting the unusual cis arrangement of the C∧N ligands. Through an integrated experimental and theoretical approach, it was possible to delineate the optoelectronic properties of cis-1. In detail, (a) a series of absorption maxima in the range 300-400 nm was assigned to metal-to-ligand charge transfer and weak and broad absorption maxima at longer wavelengths (400-500 nm) were ascribable to spin-forbidden transitions with a mixed character; (b) there was an intense red phosphorescence with emission set in the range 580-710 nm; and (c) a highest occupied molecular orbital was mainly localized on the metal and the 2-phenylpiridine ligand and a lowest unoccupied molecular orbital was localized on the N∧N ligand, with a ΔH-L set at 2.20 eV. This investigation allowed the design of light-emitting electrochemical cell (LEEC) devices endowed with good performance. The poor literature reporting on the use of cis-iridium(III) complexes in LEECs prompted us to investigate the role played by the selected cathode and the thickness of the emitting layer, as well as the doping effect exerted by ionic liquids on the performance of the devices. All the devices exhibited a deep red emission, in some cases, quite near the pure color (devices #1, #4, and #8), expanding the panorama of the iridium-based red-to-near-infrared LEEC devices. The characteristics of the devices, such as the brightness reaching values of 162 cd/m2 for device #7, suggested that the performances of cis-1 are comparable to those of trans isomers, opening new perspective toward designing a new set of luminescent materials for optoelectronic devices.

Melanin-Inspired Organic Electronics: Electroluminescence in Asymmetric Triazatruxenes.

The oxidative polymerization of 5,6-dihydroxyindoles and related hydroxyindoles at pH<3 is diverted from the usual eumelanin-forming pathway to produce mixtures of symmetric and asymmetric triazatruxenes (TATs), which could be separated and characterized for their opto-electronic properties with the aid of TD-DFT calculations. Data showed that the asymmetric isomers exhibit higher fluorescence quantum efficiencies, lower HOMO-LUMO gaps, better film homogeneity, and a more definite aggregation behavior than the symmetric counterparts, suggesting promising applications in organic electronics. The enhanced luminance exhibited by the OLED devices fabricated with blends of the synthesized TATs in poly-9-vinylcarbazole confirmed the potential of the asymmetric skeleton as new versatile platform for light-emitting materials.

Melanin-Inspired Organic Electronics: Electroluminescence in Asymmetric Triazatruxenes.

Invited for this month's cover is the group of Dr. Paola Manini from the University of Naples Federico II. The cover picture shows the concept underlying the design of a melanin-inspired electroluminescent material for OLED devices. This article is part of a well-structured research project aimed at imitating Nature's most enigmatic and fascinating functional pigments for the design and synthesis of innovative biomaterials for organic electronics applications. Read the full text of the article at 10.1002/cplu.201402444.