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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. 

Small—but finite—fluid inertia can be leveraged to generate steady flows out of liquid vibrations around an immersed interface. In engineering, external high-frequency drivers $\left({10}^2\text{–}{10}^5\mathrm{Hz}\right)$allow this inertial rectification phenomenon, known as viscous streaming, to be employed in micron-scale devices for precise flow control, particle manipulation, and spatially controlled chemistry. However, beyond artificial settings, streaming has been hypothesized to be accessible by larger-scale biological systems pertaining to lower frequencies. Then millimeter-size organisms that oscillate or pulsate cilia and appendages in the 1 to $10\mathrm{Hz}$range may be able to rectify surrounding flows, for feeding or locomotion, removing the need for external actuators, tethers, or tubing. Motivated by this potential for bio-hybrid robotic applications and biophysical exploration, here we demonstrate an living system able to produce streaming flows endogenously, autonomously, and unassisted. Computationally informed, our biological device generates oscillatory flows through the cyclic contractions of an engineered muscle tissue, shaped in the form of a torus and suspended in fluid within a microparticle image velocimetry setup. Flow patterns consistent with streaming simulations are observed for low-frequency muscle contractions $(2–4\mathrm{Hz})$, either spontaneous or light-induced, illustrating system autonomy and controllability, respectively. Thus, by connecting tissue engineering with hydrodynamics, this work provides experimental evidence of biologically powered streaming in untethered, millimeter-scale living systems, endowing bio-hybrid technology with inertial microfluidic capabilities. It also illustrates the potential of combining bio-hybrid platforms and simulations to advance both biophysical understanding and fluid mechanics. Published by the American Physical Society2025 

The industrial revolution of the 19th century marked the onset of an era of machines and robots that transformed societies. Since the beginning of the 21st century, a new generation of robots envisions similar societal transformation. These robots are biohybrid: part living and part engineered. They may self-assemble and emerge from complex interactions between living cells. While this new era of living robots presents unprecedented opportunities for positive societal impact, it also poses a host of ethical challenges. A systematic, nuanced examination of these ethical issues is of paramount importance to guide the evolution of this nascent field. Multidisciplinary fields face the challenge that inertia around collective action to address ethical boundaries may result in unexpected consequences for researchers and societies alike. In this Perspective, we i) clarify the ethical challenges associated with biohybrid robotics, ii) discuss the need for and elements of a potential governance framework tailored to this technology; and iii) propose tangible steps toward ethical compliance and policy formation in the field of biohybrid robotics. 

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. 

The field of biohybrid robotics focuses on using biological actuators to study the emergent properties of tissues and the locomotion of living organisms. On the basis of models of swimming at small size scales, we designed and fabricated a muscle-powered, flagellate swimmer. We investigate the design of a compliant mechanism based on nonlinear mechanics and its mechanical integration with a muscle ring and motor neurons. We find that within a range of anchor stiffnesses around 1 micronewton per micrometer, the homeostatic tension in muscle is insensitive to stiffness, offering greater design flexibility. The proximity of motor neurons results in a fourfold improvement in muscle contractility. Improved contractility and nonlinear design allow for a peak swimming speed about two orders of magnitude higher than previous biohybrid flagellate swimmers, reaching 0.58 body lengths per minute (86.8 micrometers per second), by a mechanism involving inertia that we verify through flow field imaging. This swimmer opens the door for a class of intermediate–Reynolds number swimmers.