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ABSTRACT Neural biocomputing is an emerging computing paradigm in which living neural networks serve as substrates for information processing, offering adaptive and energy‐efficient alternatives to conventional silicon‐based architectures. In these systems, understanding how information is written into and read out of the living substrate is essential. Stimulation and recording interfaces represent a central element for neural biocomputing, positioning electronic materials as key enabling components. This review examines material‐based strategies for interfacing with in vitro neural systems, focusing on how materials influence the input stimulation and output recording. On the input side, we discuss electrical and optical stimulation approaches, highlighting how interface chemistry and structural design using metals, conductive polymers, nanostructures, and photoactive materials control charge transfer, spatial precision, and biological compatibility. On the output side, we review advances in electrical and optical recording technologies, emphasizing soft, hydrated, and transparent materials that reduce impedance, improving signal fidelity, and enabling monitoring of 3D neural tissues and organoids. We discuss emerging multimodal platforms that integrate electrical and optical functionalities within single material systems for simultaneous stimulation and recording. By positioning electronic materials as active agents of signal encoding and decoding, this review outlines key challenges and design principles for neural interfaces in biocomputing. 

Abstract The manipulation of fragile biological tissues such as engineered cell sheets remains a major challenge for regenerative medicine and tissue engineering. Manual handling with tools like tweezers often induces wrinkling or tearing, compromising tissue integrity. Here, we present an automated cell sheet manipulator that integrates a thermoresponsive microchanneled poly(N-isopropylacrylamide) (PNIPAAm) hydrogel with an embedded microheater, mounted on a programmable three-axis motorized stage. Upon localized heating and cooling, the hydrogel undergoes rapid, reversible volumetric transitions that enable suction-based gripping and release of cell sheets within a few seconds. The custom LabVIEW interface synchronizes stage movement and thermal cycling, allowing reproducible, hands-free operation. A compliance-based Z-axis apparatus ensured uniform low-magnitude contact forces, preventing mechanical damage during transfer. Using this system, human iPSC-derived neural sheets were reliably transferred onto human brain microvascular endothelial cell (hBMEC) monolayers. Compared to manual transfer, the automated manipulator preserved cell sheet flatness and minimized micro-wrinkling, resulting in safe retention of intercellular architecture and structural integrity. This work demonstrates a robust, user-friendly platform for automated and gentle handling of delicate biological sheets. By enabling the precise stacking of engineered tissues while preserving their morphology, this system provides a promising tool for advanced biofabrication workflows, supporting defect-free 3D tissue assembly and implantation. 

Abstract Objective.Optical stimulation ofin vitroneurons requires prior transfection with light gated ion channels. This additional step brings complexity and requires optimization. Simplification of the process will ease the undertaking of studies on biological neural networks needing external stimulation.Approach.We constructed a simple platform where embryonic stem cell derived optogenetic neural spheroids, cultured and maintained separately, can be seeded on top of the primary non-optogenetic neuron cultures.Main results.We found that the primary neural network can be stimulated through the spheroids. This allows making investigations like network response dynamics and pharmacological perturbations possible.Significance.Thus, our platform provides an on-demand method to stimulate neural preparations for many different studies. 

Abstract Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro‐electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built‐in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell‐derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long‐term recording. Overall, this technology, termed “mind in vitro” to underscore the computing inspiration, provides an end‐to‐end solution that can be widely deployed due to its affordable (>10× cost reduction) and open‐source nature, catering to the expanding needs of both conventional and unconventional electrophysiology. 

Abstract Neurons in the brain communicate with each other at their synapses. It has long been understood that this communication occurs through biochemical processes. Here, we reveal a previously unrecognized paradigm wherein mechanical tension in neurons is essential for communication. Usingin vitrorat hippocampal neurons, we find that (1) neurons become tout/tensed after forming synapses resulting in a contractile neural network, and (2) without this contractility, neurons fail to fire. To measure time evolution of network contractility in 3D (not2D) extracellular matrix, we developed an ultra-sensitive force sensor with 1 nN resolution. We employed Multi-Electrode Array (MEA) and iGluSnFR, a glutamate sensor, to quantify neuronal firing at the network and at the single synapse scale, respectively. When neuron contractility is relaxed, both techniques show significantly reduced firing. Firing resumes when contractility is restored. Neural contractility may play a crucial role in memory, learning, cognition, and various neuropathologies. 

Abstract Most of the recent work in psychedelic neuroscience has been done using noninvasive neuroimaging, with data recorded from the brains of adult volunteers under the influence of a variety of drugs. While these data provide holistic insights into the effects of psychedelics on whole-brain dynamics, the effects of psychedelics on the mesoscale dynamics of neuronal circuits remain much less explored. Here, we report the effects of the serotonergic psychedelic N,N-diproptyltryptamine (DPT) on information-processing dynamics in a sample of in vitro organotypic cultures of cortical tissue from postnatal rats. Three hours of spontaneous activity were recorded: an hour of predrug control, an hour of exposure to 10-μM DPT solution, and a final hour of washout, once again under control conditions. We found that DPT reversibly alters information dynamics in multiple ways: First, the DPT condition was associated with a higher entropy of spontaneous firing activity and reduced the amount of time information was stored in individual neurons. Second, DPT also reduced the reversibility of neural activity, increasing the entropy produced and suggesting a drive away from equilibrium. Third, DPT altered the structure of neuronal circuits, decreasing the overall information flow coming into each neuron, but increasing the number of weak connections, creating a dynamic that combines elements of integration and disintegration. Finally, DPT decreased the higher order statistical synergy present in sets of three neurons. Collectively, these results paint a complex picture of how psychedelics regulate information processing in mesoscale neuronal networks in cortical tissue. Implications for existing hypotheses of psychedelic action, such as the entropic brain hypothesis, are discussed. 

Neuronal control of skeletal muscle function is ubiquitous across species for locomotion and doing work. In particular, emergent behaviors of neurons in biohybrid neuromuscular systems can advance bioinspired locomotion research. Although recent studies have demonstrated that chemical or optogenetic stimulation of neurons can control muscular actuation through the neuromuscular junction (NMJ), the correlation between neuronal activities and resulting modulation in the muscle responses is less understood, hindering the engineering of high-level functional biohybrid systems. Here, we developed NMJ-based biohybrid crawling robots with optogenetic mouse motor neurons, skeletal muscles, 3D-printed hydrogel scaffolds, and integrated onboard wireless micro–light-emitting diode (μLED)–based optoelectronics. We investigated the coupling of the light stimulation and neuromuscular actuation through power spectral density (PSD) analysis. We verified the modulation of the mechanical functionality of the robot depending on the frequency of the optical stimulation to the neural tissue. We demonstrated continued muscle contraction up to 20 minutes after a 1-minute-long pulsed 2-hertz optical stimulation of the neural tissue. Furthermore, the robots were shown to maintain their mechanical functionality for more than 2 weeks. This study provides insights into reliable neuronal control with optoelectronics, supporting advancements in neuronal modulation, biohybrid intelligence, and automation.