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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 

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules. 

Biohybrid centimeter-scale robots developed from optoelectronics and optogenetic muscles can be controlled wirelessly. 

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. 

The intriguing opportunities enabled by the use of living components in biological machines have spurred the development of a variety of muscle‐powered biohybrid robots in recent years. Among them, several generations of tissue‐engineered biohybrid walkers have been established as reliable platforms to study untethered locomotion. However, despite these advances, such technology is not mature yet, and major challenges remain. Herein, steps are taken to address two of them: the lack of systematic design approaches, common to biohybrid robotics in general, and in the case of biohybrid walkers specifically, the lack of maneuverability. A dual‐ring biobot is presented which is computationally designed and selected to exhibit robust forward motion and rotational steering. This dual‐ring biobot consists of two independent muscle actuators and a four‐legged scaffold asymmetric in the fore/aft direction. The integration of multiple muscles within its body architecture, combined with differential electrical stimulation, allows the robot to maneuver. The dual‐ring robot design is then fabricated and experimentally tested, confirming computational predictions and turning abilities. Overall, a design approach based on modeling, simulation, and fabrication exemplified in this versatile robot represents a route to efficiently engineer complex biological machines with adaptive functionalities.