Combining biological components, such as cells and tissues, with soft robotics can enable the fabrication of biological machines with the ability to sense, process signals, and produce force. An intuitive demonstration of a biological machine is one that can produce motion in response to controllable external signaling. Whereas cardiac cell-driven biological actuators have been demonstrated, the requirements of these machines to respond to stimuli and exhibit controlled movement merit the use of skeletal muscle, the primary generator of actuation in animals, as a contractile power source. Here, we report the development of 3D printed hydrogel "bio-bots" with an asymmetric physical design and powered by the actuation of an engineered mammalian skeletal muscle strip to result in net locomotion of the bio-bot. Geometric design and material properties of the hydrogel bio-bots were optimized using stereolithographic 3D printing, and the effect of collagen I and fibrin extracellular matrix proteins and insulin-like growth factor 1 on the force production of engineered skeletal muscle was characterized. Electrical stimulation triggered contraction of cells in the muscle strip and net locomotion of the bio-bot with a maximum velocity of ∼156 μm s −1 , which is over 1.5 body lengths per min. Modeling and simulation were used to understand both the effect of different design parameters on the bio-bot and the mechanism of motion. This demonstration advances the goal of realizing forward-engineered integrated cellular machines and systems, which can have a myriad array of applications in drug screening, programmable tissue engineering, drug delivery, and biomimetic machine design.bioactuator | stereolithography

Complex biological systems sense, process, and respond to their surroundings in real time. The ability of such systems to adapt their behavioral response to suit a range of dynamic environmental signals motivates the use of biological materials for other engineering applications. As a step toward forward engineering biological machines (bio-bots) capable of nonnatural functional behaviors, we created a modular light-controlled skeletal musclepowered bioactuator that can generate up to 300 μN (0.56 kPa) of active tension force in response to a noninvasive optical stimulus. When coupled to a 3D printed flexible bio-bot skeleton, these actuators drive directional locomotion (310 μm/s or 1.3 body lengths/min) and 2D rotational steering (2°/s) in a precisely targeted and controllable manner. The muscle actuators dynamically adapt to their surroundings by adjusting performance in response to "exercise" training stimuli. This demonstration sets the stage for developing multicellular bio-integrated machines and systems for a range of applications.bioactuator | stereolithography | tissue engineering | soft robotics U nderstanding complex biological systems requires uncovering the mechanisms through which integrated multicellular networks accomplish sensing, internal processing, and coordinated action in response to dynamic environmental signals. Attempting to reverse engineer these mechanisms for applications in regenerative medicine has been the focus of the burgeoning field of tissue engineering (1), and seminal advances in this field have targeted nearly every organ system in the body (2). These developments, in addition to improving the state of the art in therapeutics, have furthered our understanding of the design principles governing the organizational structure and function of natural biological systems. With this as a guide, we are ideally poised to start forward engineering biological machines, or bio-bots, capable of complex controllable nonnatural functional behaviors, thereby broadening the potential applications for building with biological materials.Before we can design bio-integrated machines for a range of applications, we must first engineer modular tissue building blocks that respond to external signals with complex functional behaviors. Observing and controlling the coordinated action of such building blocks in series and parallel will help us understand the emergent behavior of natural biological systems (3, 4). Nearly all machines require actuators, modules that convert energy into motion, to produce a measurable output in response to input stimuli. Efforts to manufacture bio-integrated actuators have targeted a range of cell types (5), including flagellated bacteria (6), cardiac muscle (7-9), and skeletal muscle (10-12). We previously demonstrated a millimeter-scale soft robotic device, or biobot, that uses the contractile force produced by electrically paced skeletal muscle to drive locomotion across a substrate (10). This bio-bot was the first demonstration of an untethered locomotive skeletal mu...

Bioresorbable electronic materials serve as foundations for implantable devices that provide active diagnostic or therapeutic function over a timeframe matched to a biological process, and then disappear within the body in a way that avoids secondary surgical extraction procedures. Approaches to power supply in these physically transient systems are critically important. This paper describes a fully biodegradable, monocrystalline silicon photovoltaic (PV) platform based on microscale cells (microcells) designed to operate at wavelengths with long penetration depths in biological tissues (red and near infrared wavelengths) such that external illumination can provide realistic levels of power. Systematic characterization and theoretical simulations of operation under porcine skin and fat establish a foundational understanding of these systems and their scalability. In vivo studies of a representative platform capable of generating ~60 W of electrical power with an open circuit voltage (V oc ) of ~4 V under 4 mm of porcine skin and fat illustrate an ability to operate blue light-emitting diodes (LEDs) as subdermal implants in rat models for 3 days. Here, the PV system fully resorbs over a period of 4 months. Histological analysis reveals that the degradation process introduces no inflammatory responses in the surrounding tissues, consistent with excellent biocompatibility of the devices, their constituent materials and degradation by-products. The results suggest the potential for using silicon photovoltaic microcells as bioresorbable power supplies for a range of transient biomedical implants.

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.