John S Forsythe’s research while affiliated with Monash University (Australia) and other places

Penetrating recording neural electrodes prepared from materials with miniaturized geometrical size could improve the longevity of implants by reducing the chronic inflammatory response. Reduced graphene oxide (rGO) microfibers with tunable porous structures have a large electrochemical surface area (ESA)/ geometrical surface area (GSA) ratio that has been reported to possess low impedance and high charge injection capacity (CIC), yet the control of the porous structure remains to be fully investigated. In this study, we introduce wet-spun rGO electrodes with pores tuned by sucrose concentrations in the coagulation bath. The electrochemical properties of thermally reduced rGO were optimized by adjusting the ratio of rGO to sucrose, resulting in significantly lower impedance, higher CIC, and higher charge storage capacity (CSC) than platinum microwires. Tensile and insertion tests confirmed that optimized electrodes had sufficient strength to ensure a 100% insertion success rate with low angle shift, thus allowing precise implantation without the need for additional mechanical enhancement. Acute in-vivo recordings from the auditory cortex found low impedance benefits from the recorded amplitude of spikes, leading to an increase in the signal-to-noise ratio (SNR). Ex-vivo recordings from hippocampal brain slices demonstrate that it is possible to record and/or stimulate with rGO electrodes with good fidelity compared with conventional electrodes.

The composition, elasticity and organization of the extracellular matrix within the central nervous system contribute to the architecture and function of the brain. From an in vitro modelling perspective, soft biomaterials are needed to mimic the three-dimensional (3D) neural microenvironments. While many studies have investigated 3D culture and neural network formation in bulk hydrogel systems, these approaches have limited ability to position cells to mimic sophisticated brain architectures. In this study, cortical neurons and astrocytes acutely isolated from the brains of rats are bioprinted in a hydrogel to form 3D neuronal constructs. Successful bioprinting of cellular and acellular strands in a multi-bioink approach allow the subsequent formation of gray- and white-matter tracts reminiscent of cortical structures. Immunohistochemistry shows the formation of dense, 3D axon networks. Calcium signalling and extracellular electrophysiology in these 3D neuronal networks confirm spontaneous activity in addition to evoked activities under pharmacological and electrical stimulation. Our system and bioprinting approaches are capable of fabricating soft, free-standing neuronal structures of different bioink and cell types with high resolution and throughput, which provides a promising platform for understanding fundamental questions of neural networks, engineering neuromorphic circuits and for in vitro drug screening. This article is protected by copyright. All rights reserved.

Ultrasound-guided needle interventions are common procedures in medicine, and tissue-mimicking phantoms are widely used for simulation training to bridge the gap between theory and clinical practice in a controlled environment. This review assesses tissue-mimicking materials from 24 studies as candidates for a high-fidelity ultrasound phantom, including methods for evaluating relevant acoustic and mechanical properties and to what extent the reported materials mimic the superficial layers of biological tissue. Speed of sound, acoustic attenuation, Young's modulus, hardness, needle interaction forces, training efficiency and material limitations were systematically evaluated. Although gelatin and agar have the closest acoustic values to tissue, mechanical properties are limited, and strict storage protocols must be employed to counteract dehydration and microbial growth. Polyvinyl chloride (PVC) has superior mechanical properties and is a suitable alternative if durability is desired and some ultrasound realism to human tissue may be sacrificed. Polyvinyl alcohol (PVA), while also requiring hydration, performs well across all categories. Furthermore, we propose a framework for the evaluation of future ultrasound-guided needle intervention tissue phantoms to increase the fidelity of training programs and thereby improve clinical performance.

Many in vitro models of neural physiology utilize neuronal networks established on two-dimensional substrates. Despite the simplicity of these 2D neuronal networks, substrate stiffness may influence cell morphology, network interactions and how neurons communicate and function. With this perspective, 3D gel encapsulation is a powerful to recapitulating aspects of in vivo features, yet such an approach is often limited in terms of the level of resolution and feature size relevant for modelling aspects of brain architecture. Here, we report 3D bioplotting of rat primary cortical neural cells using a hydrogel system comprising gelatin norbornene (GelNB) and poly (ethylene glycol) dithiol (PEGdiSH). This bioink benefits from a rapid photo-click chemistry, yielding 8-layer crosshatch neural scaffolds and a filament width of 350 µm. The printability of this system depends on hydrogel concentration, printing temperature, extrusion pressure and speed. These parameters were studied via quantitative comparison between rheology and filament dimensions to determine the optimal printing conditions. Under optimal conditions, cell viability of bioprinted primary cortical neurons at day 1 (68 ± 2%) and at day 7 (68 ± 1%) were comparable to the 2D control group (72 ± 7%). The present study relates material rheology and filament dimensions to generate compliant free-standing neural constructs through bioplotting of low-concentration GelNB-PEGdiSH, which may provide a step forward to study 3D neuronal function and network formation.