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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Tissue-on-chip systems represent promising platforms for monitoring and controlling tissue functions in vitro for various purposes in biomedical research. The two-dimensional (2D) layouts of these constructs constrain the types of interactions that can be studied and limit their relevance to three-dimensional (3D) tissues. The development of 3D electronic scaffolds and microphysiological devices with geometries and functions tailored to realistic 3D tissues has the potential to create important possibilities in advanced sensing and control. This study presents classes of compliant 3D frameworks that incorporate microscale strain sensors for high-sensitivity measurements of contractile forces of engineered optogenetic muscle tissue rings, supported by quantitative simulations. Compared with traditional approaches based on optical microscopy, these 3D mechanical frameworks and sensing systems can measure not only motions but also contractile forces with high accuracy and high temporal resolution. Results of active tension force measurements of engineered muscle rings under different stimulation conditions in long-term monitoring settings for over 5 wk and in response to various chemical and drug doses demonstrate the utility of such platforms in sensing and modulation of muscle and other tissues. Possibilities for applications range from drug screening and disease modeling to biohybrid robotic engineering.

Integration of conductive electrodes with 3D tissue models can have great potential for applications in bioelectronics, drug screening, and implantable devices. As conventional electrodes cannot be easily integrated on 3D, polymeric, and biocompatible substrates, alternatives are highly desirable. Graphene offers significant advantages over conventional electrodes due to its mechanical flexibility and robustness, biocompatibility, and electrical properties. However, the transfer of chemical vapor deposition graphene onto millimeter scale 3D structures is challenging using conventional wet graphene transfer methods with a rigid poly (methyl methacrylate) (PMMA) supportive layer. Here, a biocompatible 3D graphene transfer method onto 3D printed structure using a soft poly ethylene glycol diacrylate (PEGDA) supportive layer to integrate the graphene layer with a 3D engineered ring of skeletal muscle tissue is reported. The use of softer PEGDA supportive layer, with a 105 times lower Young's modulus compared to PMMA, results in conformal integration of the graphene with 3D printed pillars and allows electrical stimulation and actuation of the muscle ring with various applied voltages and frequencies. The graphene integration method can be applied to many 3D tissue models and be used as a platform for electrical interfaces to 3D biological tissue system.

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.