The integration of muscle cells with soft robotics in recent years has led to the development of biohybrid machines capable of untethered locomotion. A major frontier that currently remains unexplored is neuronal actuation and control of such muscle-powered biohybrid machines. As a step toward this goal, we present here a biohybrid swimmer driven by on-board neuromuscular units. The body of the swimmer consists of a free-standing soft scaffold, skeletal muscle tissue, and optogenetic stem cell-derived neural cluster containing motor neurons. Myoblasts embedded in extracellular matrix self-organize into a muscle tissue guided by the geometry of the scaffold, and the resulting muscle tissue is cocultured in situ with a neural cluster. Motor neurons then extend neurites selectively toward the muscle and innervate it, developing functional neuromuscular units. Based on this initial construct, we computationally designed, optimized, and implemented light-sensitive flagellar swimmers actuated by these neuromuscular units. Cyclic muscle contractions, induced by neural stimulation, drive time-irreversible flagellar dynamics, thereby providing thrust for untethered forward locomotion of the swimmer. Overall, this work demonstrates an example of a biohybrid robot implementing neuromuscular actuation and illustrates a path toward the forward design and control of neuron-enabled biohybrid machines.

Surgeons typically rely on their past training and experiences as well as visual aids from medical imaging techniques such as magnetic resonance imaging (MRI) or computed tomography (CT) for the planning of surgical processes. Often, due to the anatomical complexity of the surgery site, two dimensional or virtual images are not sufficient to successfully convey the structural details. For such scenarios, a 3D printed model of the patient's anatomy enables personalized preoperative planning. This paper reviews critical aspects of 3D printing for preoperative planning and surgical training, starting with an overview of the process-flow and 3D printing techniques, followed by their applications spanning across multiple organ systems in the human body. State of the art in these technologies are described along with a discussion of current limitations and future opportunities.

Advancing biologically driven soft robotics and actuators will involve employing different scaffold geometries and cellular constructs to enable a controllable emergence for increased production of force. By using hydrogel scaffolds and muscle tissue, soft biological robotic actuators that are capable of motility have been successfully engineered with varying morphologies. Having the flexibility of altering geometry while ensuring tissue viability can enable advancing functional output from these machines through the implementation of new construction concepts and fabrication approaches. This study reports a forward engineering approach to computationally design the next generation of biological machines via direct numerical simulations. This was subsequently followed by fabrication and characterization of high force producing biological machines. These biological machines show millinewton forces capable of driving locomotion at speeds above 0.5 mm s −1 . It is important to note that these results are predicted by computational simulations, ultimately showing excellent agreement of the predictive models and experimental results, further providing the ability to forward design future generations of these biological machines. This study aims to develop the building blocks and modular technologies capable of scaling force and complexity of these devices for applications toward solving real world problems in medicine, environment, and manufacturing.

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Neuronal control of skeletal muscle bioactuators represents a critical milestone toward the realization of future biohybrid machines that may generate complex motor patterns and autonomously navigate through their environment. Animals achieve these feats using neural networks that generate robust firing patterns and coordinate muscle activity through neuromuscular units. Here, we designed a versatile 3D neuron-muscle co-culture platform to serve as a test-bed for neuromuscular bioactuators. We used our platform in conjunction with microelectrode array electrophysiology to study the roles of synergistic interactions in the co-development of neural networks and muscle tissues. Our platform design enables co-culture of a neuronal cluster with up to four target muscle actuators, as well as quantification of muscle contraction forces. Using engineered muscle tissue targets, we first demonstrated the formation of functional neuromuscular bioactuators. We then investigated possible roles of long-range interactions in neuronal outgrowth patterns and observed preferential outgrowth toward muscles compared to the acellular matrix or fibroblasts, indicating muscle-specific chemotactic cues acting on motor neurons. Next, we showed that co-cultured muscle strips exhibited significantly higher spontaneous contractility as well as improved sarcomere assembly compared to muscles cultured alone. Finally, we performed microelectrode array measurements on neuronal cultures, which revealed that muscle-conditioned medium enhances overall neural firing rates and the emergence of synchronous bursting patterns. Overall, our study illustrates the significance of neuron-muscle cross talk for the in vitro development of neuromuscular bioactuators.