Neurological diseases are leading causes of death globally and disability-adjusted life years (DALYs) globally. Because of this, urgency in providing technologies and essential medicines to tackle this issue is currently recognized as key in reversing this trend. Global health strategies have recognized tissue engineering as a pillar element in progressing both neurological disease research and therapy discovery. Over time, various biomaterials have been developed with a few barriers appearing along the way when considering translation for routine neurological disorders research and therapy. These barriers include accessibility, sustainability, cost-effectiveness and affordability. In this review, we discuss how biopolymers, namely biomimetic advanced biopolymers composites have emerged to answer this issue. We will explore various types of biomimetic nanocellulose-based, self-assembling peptides, glycosaminoglycan composite, advanced functionalized nanoparticles amongst others are used to create a range of innovative state-of -the-art neuronal models that can be employed for neuronal disease investigation and therapy. Finally, we will review the current factors enabling and hindering their translation and scalability (e.g. manufacturing, characterization and commercialization) and provide a Research and Development Roadmap that can be explored to facilitate their development and provision to answer the pressing global need for these technologies in positively impacting neurological disorders.

This study investigates the electrochemical behavior of GelMA-based hydrogels and their interactions with PC12 neural cells under electrical stimulation in the presence of conducting substrates. Focusing on indium tin oxide (ITO), platinum, and gold mylar substrates supporting conductive scaffolds composed of hydrogel, graphene oxide, and gold nanorods, we explored how the substrate materials affect scaffold conductivity and cell viability. We examined the impact of an optimized electrical stimulation protocol on the PC12 cell viability. According to our findings, substrate selection significantly influences conductive hydrogel behavior, affecting cell viability and proliferation as a result. In particular, the ITO substrates were found to provide the best support for cell viability with an average of at least three times higher metabolic activity compared to platinum and gold mylar substrates over a 7 day stimulation period. The study offers new insights into substrate selection as a platform for neural cell stimulation and underscores the critical role of substrate materials in optimizing the efficacy of neural interfaces for biomedical applications. In addition to extending existing work, this study provides a robust platform for future explorations aimed at tailoring the full potential of tissue-engineered neural interfaces.

The development of neural organoids—three-dimensional constructs of neural tissue—resulted in significant advances in neurophysiological understandings, as well raising key ethical concerns. Sawai et al. (2022) discuss the use of these neural organoids, proposing policies to regulate this technology. The most pressing issue arises in the proposed metrics for assessing phenomenological consciousness and how they may be related to neural organoids. Secondary is their application of the precautionary principle. Our commentary seeks to position these points raised by Sawai et al. (2022) in the broader context of research, including recent evidence that lab-grown human brain cells are able to engage in enactive learning, while embodied in a virtual world through real-time closed-loop electrophysiological stimulation and recording (Kagan et al. 2021).

A bstract Amongst the characteristics about information processing in the brain, observations of dynamic near-critical states have generated significant interest. However, theoretical and experimental limitations have precluded a definite answer about when and why neural criticality arises. To explore this topic, we used an in vitro neural network of cortical neurons that was trained to play a simplified game of ‘Pong’. We demonstrate that critical dynamics emerge when neural networks receive task-related structured sensory input, reorganizing the system to a near-critical state. Additionally, better task performance correlated with proximity to critical dynamics. However, criticality alone is insufficient for a neuronal network to demonstrate learning in the absence of additional information regarding the consequences of previous actions. These findings have compelling implications for the role of neural criticality.

Amongst the characteristics about information processing in the brain, observations of dynamic near-critical states have generated significant interest. However, theoretical and experimental limitations have precluded a definite answer about when and why neural criticality arises. To explore this topic, we used an in vitro neural network of cortical neurons that was trained to play a simplified game of ‘Pong’. We demonstrate that critical dynamics emerge when neural networks receive task-related structured sensory input, reorganizing the system to a near-critical state. Additionally, better task performance correlated with proximity to critical dynamics. However, criticality alone is insufficient for a neuronal network to demonstrate learning in the absence of additional information regarding the consequences of previous actions. These findings have compelling implications for the role of neural criticality.

For decades, electrode-tissue interfaces are pursued to establish electrical stimulation as a reliable means to control neuronal cells behavior. However, spreading of electrical currents in tissues limits its spatial precision. Thus, optical cues, such as near-infrared (NIR) light, are explored as alternatives. Presently, NIR stimulation requires higher energy input than electrical methods despite introduction of light absorbers, e.g., gold nanoparticles. As potential solution, NIR and electrical costimulation are proposed but with limited interfaces capable of sustaining this stimulation technique. Here, a novel electroactive nanocomposite with photoactive properties in the NIR range is constructed by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysulfosuccinimide sodium (EDC)/NHS conjugation of liquid crystal graphene oxide (LCGO) to protein-coated gold nanorods (AuNR). The liquid crystal graphene oxide-gold nanorod nanocomposite (LCGO-AuNR) is fabricated into a hydrophilic electrode-coating via drop-casting, making it appropriate for versatile electrode-tissue interface fabrication. UV-vis spectrophotometry results demonstrate that LCGO-AuNR presents an absorbance peak at 798 nm (NIR range). Cyclic voltammetry measurements further confirm its electroactive capacitive properties. Furthermore, LCGO-AuNR coating supports cell adhesion, proliferation, and differentiation of NG108-15 neuronal cells. This biocompatible interface is anticipated, with ideal electrical and optical properties for NIR and electrical costimulation, to enable further development of the technique for energy-efficient and precise neuronal cell modulation.

For decades, electrode–tissue interfaces are pursued to establish electrical stimulation as a reliable means to control neuronal cells behavior. However, spreading of electrical currents in tissues limits its spatial precision. Thus, optical cues, such as near-infrared (NIR) light, are explored as alternatives. Presently, NIR stimulation requires higher energy input than electrical methods despite introduction of light absorbers, e.g., gold nanoparticles. As potential solution, NIR and electrical costimulation are proposed but with limited interfaces capable of sustaining this stimulation technique. Here, a novel electroactive nanocomposite with photoactive properties in the NIR range is constructed by N -(3-dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride/ N -hydroxysulfosuccinimide sodium (EDC)/NHS conjugation of liquid crystal graphene oxide (LCGO) to protein-coated gold nanorods (AuNR). The liquid crystal graphene oxide–gold nanorod nanocomposite (LCGO–AuNR) is fabricated into a hydrophilic electrode-coating via drop-casting, making it appropriate for versatile electrode–tissue interface fabrication. UV–vis spectrophotometry results demonstrate that LCGO–AuNR presents an absorbance peak at 798 nm (NIR range). Cyclic voltammetry measurements further confirm its electroactive capacitive properties. Furthermore, LCGO–AuNR coating supports cell adhesion, proliferation, and differentiation of NG108-15 neuronal cells. This biocompatible interface is anticipated, with ideal electrical and optical properties for NIR and electrical costimulation, to enable further development of the technique for energy-efficient and precise neuronal cell modulation.