On-Site Formation of Functional Dopaminergic Presynaptic Terminals on Neuroligin-2-Modified Gold-Coated Microspheres.

Advancements in neural interface technologies have enabled the direct connection of neurons and electronics, facilitating chemical communication between neural systems and external devices. One promising approach is a synaptogenesis-involving method, which offers an opportunity for synaptic signaling between these systems. Janus synapses, one type of synaptic interface utilizing synaptic cell adhesion molecules for interface construction, possess unique features that enable the determination of location, direction of signal flow, and types of neurotransmitters involved, promoting directional and multifaceted communication. This study presents the first successful establishment of a Janus synapse between dopaminergic (DA) neurons and abiotic substrates by using a neuroligin-2 (NLG2)-mediated synapse-inducing method. NLG2 immobilized on gold-coated microspheres can induce synaptogenesis upon contact with spatially isolated DA axons. The induced DA Janus synapses exhibit stable synaptic activities comparable to that of native synapses over time, suggesting their suitability for application in neural interfaces. By calling for DA presynaptic organizations, the NLG2-immobilized abiotic substrate is a promising tool for the on-site detection of synaptic dopamine release.

Neuroligin-1-Modified Electrodes for Specific Coupling with a Presynaptic Neuronal Membrane.

Coordination of synapses onto electrodes with high specificity and maintaining a stable and long-lasting interface have importance in the field of neural interfaces. One potential approach is to present ligands on the surface of electrodes that would be bound through a protein-protein interaction to specific areas of neuronal cells. Here, we functionalize electrode surfaces with genetically engineered neuroligin-1 protein and demonstrate the formation of a nascent presynaptic bouton upon binding to neurexin-1 ß on the presynaptic membrane of neurons. The resulting synaptically connected electrode shows an assembly of presynaptic proteins and comparable exocytosis kinetics to that of native synapses. Importantly, a neuroligin-1-induced synapse-electrode interface exhibits type specificity and structural robustness. We envision that the use of synaptic adhesion proteins in modified neural electrodes may lead to new approaches in the interfacing of neural circuity and electronics.

Robust Induced Presynapse on Artificial Substrates as a Neural Interfacing Method.

Over the recent years, the development of neural interface systems has stuck to using electrical cues to stimulate neurons and read out neural signals, although neurons relay signals via chemical release and recognition at synapses. In addition, conventional neural interfaces are vulnerable to cell migration and glial encapsulation due to the absence of connection anchoring the neuron into the device unlike synapses, which are firmly sustained by protein bonding. To close this discrepancy, we conducted an intensive investigation into the induced synapse interface by employing engineered synaptic proteins from a neural interface perspective. The strong potential of induced synaptic differentiation as an emerging neural interfacing technique is demonstrated by exploring its structural features, chemical release kinetics, robustness, and scalability to the brain tissue. We show that the exocytosis kinetics of induced synapses is similar to that of endogenous synapses. Moreover, induced synapses show remarkable stability, despite cell migration and growth. The synapse-inducing technique has broad applications to cultured hippocampal and cortex tissues and suggests a promising method to integrate neural circuits with digital elements.

Anti-inflammatory and Antibacterial Effects of Covalently Attached Biomembrane-Mimic Polymer Grafts on Gore-Tex Implants.

Expanded polytetrafluoroethylene (ePTFE), also known as Gore-Tex, is widely used as an implantable biomaterial in biomedical applications because of its favorable mechanical properties and biochemical inertness. However, infection and inflammation are two major complications with ePTFE implantations, because pathogenic bacteria can inhabit the microsized pores, without clearance by host immune cells, and the limited biocompatibility can induce foreign body reactions. To minimize these complications, we covalently grafted a biomembrane-mimic polymer, poly(2-methacryloyloxylethyl phosphorylcholine) (PMPC), by partial defluorination followed by UV-induced polymerization with cross-linkers on the ePTFE surface. PMPC grafting greatly reduced serum protein adsorption as well as fibroblast adhesion on the ePTFE surface. Moreover, the PMPC-grafted ePTFE surface exhibited a dramatic inhibition of the adhesion and growth of Staphylococcus aureus, a typical pathogenic bacterium in ePTFE implants, in the porous network. On the basis of an analysis of immune cells and inflammation-related factors, i.e., transforming growth factor-ß (TGF-ß) and myeloperoxidase (MPO), we confirmed that inflammation was efficiently alleviated in tissues around PMPC-grafted ePTFE plates implanted in the backs of rats. Covalent PMPC may be an effective strategy for promoting anti-inflammatory and antibacterial functions in ePTFE implants and to reduce side effects in biomedical applications of ePTFE.

Development of anti-biofouling interface on hydroxyapatite surface by coating zwitterionic MPC polymer containing calcium-binding moieties to prevent oral bacterial adhesion.

UNLABELLED: The purpose of the present study is to synthesize a 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer capable of being immobilized on the tooth surface to prevent oral bacterial adhesion. The strategy is to develop an MPC-based polymer with Ca(2+)-binding moieties, i.e., phosphomonoester groups, for stronger binding with hydroxyapatite (HA) of the tooth surface. To this end, a 2-methacryloyloxyethyl phosphate (MOEP) monomer was synthesized and copolymerized with MPC by free radical polymerization. The coating efficiency of the synthesized polymer, MPC-ran-MOEP (abbreviated as PMP) with varied composition, onto a HA surface was estimated by means of contact angle measurement and X-ray photoelectron spectroscopy. The anti-biofouling nature of PMP-coated HA surfaces was estimated by analyzing protein adsorption, cell adhesion, and Streptococcus mutans adhesion. As a result, HA surface coated with a copolymer containing around 50% MPC (PMP50) showed the best performance in preventing protein adsorption and the downstream cell and bacterial adhesion. STATEMENT OF SIGNIFICANCE: Preparation of anti-biofouling surface on the tooth enamel is the key technique to prevent dental and periodontal diseases, which are closely related with the biofilm formation that induced by the adsorption of salivary proteins and the adhesion of oral bacteria on the tooth surface. In this research, a PMP copolymer with an optimized ratio of zwitterionic and Ca(2+)-binding moieties could form a highly effective and robust anti-biofouling surface on HA surfaces by a simple coating method. The PMP-coated surface with high stability can provide a new strategy for an anti-adsorptive and anti-bacterial platform in dentistry and related fields.

One-dimensional semiconductor nanostructure based thin-film partial composite formed by transfer implantation for high-performance flexible and printable electronics at low temperature.

Having high bending stability and effective gate coupling, the one-dimensional semiconductor nanostructures (ODSNs)-based thin-film partial composite was demonstrated, and its feasibility was confirmed through fabricating the Si NW thin-film partial composite on the poly(4-vinylphenol) (PVP) layer, obtaining uniform and high-performance flexible field-effect transistors (FETs). With the thin-film partial composite optimized by controlling the key steps consisting of the two-dimensional random dispersion on the hydrophilic substrate of ODSNs and the pressure-induced transfer implantation of them into the uncured thin dielectric polymer layer, the multinanowire (NW) FET devices were simply fabricated. As the NW density increases, the on-current of NW FETs increases linearly, implying that uniform NW distribution can be obtained with random directions over the entire region of the substrate despite the simplicity of the drop-casting method. The implantation of NWs by mechanical transfer printing onto the PVP layer enhanced the gate coupling and bending stability. As a result, the enhancements of the field-effect mobility and subthreshold swing and the stable device operation up to a 2.5 mm radius bending situation were achieved without an additional top passivation.