Biohybrid robotics: From the nanoscale to the macroscale

Biohybrid robotics is a field in which biological entities are combined with artificial materials in order to obtain improved performance or features that are difficult to mimic with hand-made materials. Three main level of integration can be envisioned depending on the complexity of the biological entity, ranging from the nanoscale to the macroscale. At the nanoscale, enzymes that catalyze biocompatible reactions can be used as power sources for self-propelled nanoparticles of different geometries and compositions, obtaining rather interesting active matter systems that acquire importance in the biomedical field as drug delivery systems. At the microscale, single enzymes are substituted by complete cells, such as bacteria or spermatozoa, whose self-propelling capabilities can be used to transport cargo and can also be used as drug delivery systems, for in vitro fertilization practices or for biofilm removal. Finally, at the macroscale, the combinations of millions of cells forming tissues can be used to power biorobotic devices or bioactuators by using muscle cells. Both cardiac and skeletal muscle tissue have been part of remarkable examples of untethered biorobots that can crawl or swim due to the contractions of the tissue and current developments aim at the integration of several types of tissue to obtain more realistic biomimetic devices, which could lead to the next generation of hybrid robotics. Tethered bioactuators, however, result in excellent candidates for tissue models for drug screening purposes or the study of muscle myopathies due to their three-dimensional architecture

Biological Organisms as End Effectors

In robotics, an end effector is a device at the end of a robotic arm designed to interact with the environment. Effectively, it serves as the hand of the robot, carrying out tasks on behalf of humans. But could we turn this concept on its head and consider using living organisms themselves as end-effectors? This paper introduces a novel idea of using whole living organisms as end effectors for robotics. We showcase this by demonstrating that pill bugs and chitons -- types of small, harmless creatures -- can be utilized as functional grippers. Crucially, this method does not harm these creatures, enabling their release back into nature after use. How this concept may be expanded to other organisms and applications is also discussed.Comment: 11 pages, 8 figure

Biohybrid swimmers at low Reynolds number powered by tissue-engineered neuromuscular units

Biohybrid machines are engineered systems which are built by integrating biological cells with synthetic materials and components. Development of biohybrid machines utilizes the classical engineering modalities of design, modeling, prototype fabrication, testing, and iteration, but also draws from a toolbox that includes biological cells and materials. This enables a range of exciting possibilities since biological systems can develop via self-organization, function autonomously, and monitor and adapt to their environments. Pioneering studies on biohybrid machines have demonstrated the development of devices powered by muscle cells, capable of locomotion, pumping, and micromanipulation. A currently emerging frontier in the field is the integration of neuronal control. A wide range of complex animal behaviors are orchestrated by the nervous system which interfaces the body with the environment through sensing, information processing, and coordinating motor activity. Hence, the integration of neurons may enable the development of autonomous biohybrid machines capable of higher-level functionalities such as sensing, memory, and adaptation. The focus of this dissertation is on the implementation of neuronal actuation in muscle powered biohybrid machines. Firstly, we develop an experimental bioactuator platform to study the in vitro development of neuromuscular units. Engineered skeletal muscle tissues, anchored to compliant pillars, are co-cultured on the platform with optogenetic stem cell-derived neuronal clusters containing motor neurons. The motor neurons extend axons and innervate the muscle fibers, forming functional neuromuscular units. Our study illustrates several outcomes of synergistic interactions between the muscles and neurons. Muscles co-cultured with neurons exhibit significantly higher contraction force and cytoskeletal maturation compared to muscles cultured alone. Neurons self-organize into networks which generate synchronous bursting patterns, the development of which is facilitated by muscle-secreted soluble factors. Next, we implement our neuron-muscle co-culture approach on a free-standing compliant scaffold containing slender flagella, to demonstrate the first example of a biohybrid swimmer powered by neuromuscular units. Optogenetic stimulation of motor neurons evokes periodic muscle contractions, and the swimmer is driven by the resulting time-irreversible deformations of the flagella, a common mechanism of propulsion at low Reynolds number. Lastly, we investigate potential design strategies for improving swimming performance, assisted by analytical and computational models. Our models predict that the swimming speed of our initial prototype can be improved by up to two orders of magnitude by redesigning the swimmer scaffold to reduce drag and increase actuation amplitude

Soft Perfusable Device to Culture Skeletal Muscle 3D Constructs in Air

Devices for in vitro culture of three-dimensional (3D) skeletal muscle tissues have multiple applications, including tissue engineering and muscle-powered biorobotics. In both cases, it is crucial to recreate a biomimetic environment by using tailored scaffolds at multiple length scales and to administer prodifferentiative biophysical stimuli (e.g., mechanical loading). On the contrary, there is an increasing need to develop flexible biohybrid robotic devices capable of maintaining their functionality beyond laboratory settings. In this study, we describe a stretchable and perfusable device to sustain cell culture and maintenance in a 3D scaffold. The device mimics the structure of a muscle connected to two tendons: Tendon−Muscle−Tendon (TMT). The TMT device is composed of a soft (E ∼ 6 kPa) porous (pore diameter: ∼650 μm) polyurethane scaffold, encased within a compliant silicone membrane to prevent medium evaporation. Two tendon-like hollow channels interface the scaffold with a fluidic circuit and a stretching device. We report an optimized protocol to sustain C2C12 adhesion by coating the scaffold with polydopamine and fibronectin. Then, we show the procedure for the soft scaffold inclusion in the TMT device, demonstrating the device’s ability to bear multiple cycles of elongations, simulating a protocol for cell mechanical stimulation. By using computational fluid dynamic simulations, we show that a flow rate of 0.62 mL/min ensures a wall shear stress value safe for cells (<2 Pa) and 50% of scaffold coverage by an optimal fluid velocity. Finally, we demonstrate the effectiveness of the TMT device to sustain cell viability under perfusion for 24 h outside of the CO2 incubator. We believe that the proposed TMT device can be considered an interesting platform to combine several biophysical stimuli, aimed at boosting skeletal muscle tissue differentiation in vitro, opening chances for the development of muscle-powered biohybrid soft robots with long-term operability in real-world environments

Hybrid bio-robotics: from the nanoscale to the macroscale

[eng] Hybrid bio-robotics is a discipline that aims at integrating biological entities with synthetic materials to incorporate features from biological systems that have been optimized through millions of years of evolution and are difficult to replicate in current robotic systems. We can find examples of this integration at the nanoscale, in the field of catalytic nano- and micromotors, which are particles able to self-propel due to catalytic reactions happening in their surface. By using enzymes, these nanomotors can achieve motion in a biocompatible manner, finding their main applications in active drug delivery. At the microscale, we can find single-cell bio-swimmers that use the motion capabilities of organisms like bacteria or spermatozoa to transport microparticles or microtubes for targeted therapeutics or bio-film removal. At the macroscale, cardiac or skeletal muscle tissue are used to power small robotic devices that can perform simple actions like crawling, swimming, or gripping, due to the contractions of the muscle cells. This dissertation covers several aspects of these kinds of devices from the nanoscale to the macro-scale, focusing on enzymatically propelled nano- and micromotors and skeletal muscle tissue bio-actuators and bio-robots. On the field of enzymatic nanomotors, there is a need for a better description of their dynamics that, consequently, might help understand their motion mechanisms. Here, we focus on several examples of nano- and micromotors that show complex dynamics and we propose different strategies to analyze their motion. We develop a theoretical framework for the particular case of enzymatic motors with exponentially decreasing speed, which break the assumptions of constant speed of current methods of analysis and need different strategies to characterize their motion. Finally, we consider the case of enzymatic nanomotors moving in complex biological matrices, such as hyaluronic acid, and we study their interactions and the effects of the catalytic reaction using dynamic light scattering, showing that nanomotors with negative surface charge and urease-powered motion present enhanced parameters of diffusion in hyaluronic acid. Moving towards muscle-based robotics, we investigate the application of 3D bioprinting for the bioengineering of skeletal muscle tissue. We demonstrate that this technique can yield well-aligned and functional muscle fibers that can be stimulated with electric pulses. Moreover, we develop and apply a novel co-axial approach to obtain thin and individual muscle fibers that resemble the bundle-like organization of native skeletal muscle tissue. We further exploit the versatility of this technique to print several types of materials in the same process and we fabricate bio-actuators based on skeletal muscle tissue with two soft posts. Due to the deflection of these cantilevers when the tissue contracts upon stimulation, we can measure the generated forces, therefore obtaining a force measurement platform that could be useful for muscle development studies or drug testing. With these applications in mind, we study the adaptability of muscle tissue after applying various exercise protocols based on different stimulation frequencies and different post stiffness, finding an increase of the force generation, especially at medium frequencies, that resembles the response of native tissue. Moreover, we adapt the force measurement platform to be used with human-derived myoblasts and we bioengineer two models of young and aged muscle tissue that could be used for drug testing purposes. As a proof of concept, we analyze the effects of a cosmetic peptide ingredient under development, focusing on the kinematics of high stimulation contractions. Finally, we present the fabrication of a muscle-based bio-robot able to swim by inertial strokes in a liquid interface and a nanocomposite-laden bio-robot that can crawl on a surface. The first bio-robot is thoroughly characterized through mechanical simulations, allowing us to optimize the skeleton, based on a serpentine or spring-like structure. Moreover, we compare the motion of symmetric and asymmetric designs, demonstrating that, although symmetric bio-robots can achieve some motion due to spontaneous symmetry breaking during its self-assembly, asymmetric bio-robots are faster and more consistent in their directionality. The nanocomposite-laden crawling bio-robot consisted of embedded piezoelectric boron nitride nanotubes that improved the differentiation of the muscle tissue due to a feedback loop of piezoelectric effect activated by the same spontaneous contractions of the tissue. We find that bio-robots with those nanocomposites achieve faster motion and stronger force outputs, demonstrating the beneficial effects in their differentiation. This research presented in this thesis contributes to the development of the field of bio-hybrid robotic devices. On enzymatically propelled nano- and micromotors, the novel theoretical framework and the results regarding the interaction of nanomotors with complex media might offer useful fundamental knowledge for future biomedical applications of these systems. The bioengineering approaches developed to fabricate murine- or human-based bio-actuators might find applications in drug screening or to model heterogeneous muscle diseases in biomedicine using the patient’s own cells. Finally, the fabrication of bio-hybrid swimmers and nanocomposite crawlers will help understand and improve the swimming motion of these devices, as well as pave the way towards the use of nanocomposite to enhance the performance of future actuators.[spa] La bio-robótica híbrida es una disciplina cuyo objetivo es la integración de entidades biológicas con materiales sintéticos para superar los desafíos existentes en el campo de la robótica blanda, incorporando características de los sistemas biológicos que han sido optimizadas durante millones de años de evolución natural y no son fáciles de reproducir artificialmente. Esta tesis cubre varios aspectos de este tipo de dispositivos desde la nanoescala a la macroescala, enfocándose en nano- y micromotores propulsados enzimáticamente y bio-actuadores y bio-robots basados en tejido muscular esquelético. En el campo de nanomotores enzimáticos, existe la necesidad de encontrar mejores modelos que puedan describir la dinámica de su movimiento para llegar a entender sus mecanismos de propulsión subyacentes. Aquí, nos enfocamos en diversos ejemplos de nano- y micromotores que muestran dinámicas de movimiento complejas y proponemos diferentes estrategias que se pueden utilizar para analizar y caracterizar este movimiento. Moviéndonos hacia robots basados en células musculares, investigamos la aplicación de la técnica de bioimpresión en 3D para la biofabricación de músculo esquelético. Demostramos que esta técnica puede producir fibras musculares funcionales y bien alineadas que puede ser estimuladas y contraerse con pulsos eléctricos. Investigamos la versatilidad de esta técnica para imprimir varios tipos de materiales en el mismo proceso y fabricamos bio-actuadores basados en músculo esquelético. Debido a los movimientos de unos postes gracias a las contracciones musculares, podemos obtener medidas de la fuerza ejercida, obteniendo una plataforma de medición de fuerzas que podría ser de utilidad para estudios sobre el desarrollo del músculo o para testeo de fármacos. Finalmente, presentamos la fabricación de un bio-robot basado en músculo esquelético capaz de nadar en la superficie de un líquido y un bio-robot con nanocompuestos incrustados que puede arrastrarse por una superficie sólida. El primer de ellos es minuciosamente caracterizado a través de simulaciones mecánicas, permitiéndonos optimizar su esqueleto, basado en una estructura tipo serpentina o muelle. El segundo bio-robot contiene nanotubos piezoeléctricos incrustados en su tejido, los cuales ayudan en la diferenciación del músculo debido a una retroalimentación basada en su efecto piezoeléctrico y activada por las contracciones espontáneas del tejido. Mostramos que estos bio-robots pueden generar un movimiento más rápido y una mayor generación de fuerza, demostrando los efectos beneficiales en la diferenciación del tejido

Low-power microelectronics embedded in live jellyfish enhance propulsion

Artificial control of animal locomotion has the potential to simultaneously address longstanding challenges to actuation, control, and power requirements in soft robotics. Robotic manipulation of locomotion can also address previously inaccessible questions about organismal biology otherwise limited to observations of naturally occurring behaviors. Here, we present a biohybrid robot that uses onboard microelectronics to induce swimming in live jellyfish. Measurements demonstrate that propulsion can be substantially enhanced by driving body contractions at an optimal frequency range faster than natural behavior. Swimming speed can be enhanced nearly threefold, with only a twofold increase in metabolic expenditure of the animal and 10 mW of external power input to the microelectronics. Thus, this biohybrid robot uses 10 to 1000 times less external power per mass than other aquatic robots reported in literature. This capability can expand the performance envelope of biohybrid robots relative to natural animals for applications such as ocean monitoring

The bioprinting roadmap

This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field

Toward an Agent-Agnostic Transmission Model: Synthesizing Anthropocentric and Technocentric Paradigms in Communication

Technological and social evolutions have prompted operational, phenomenological, and ontological shifts in communication processes. These shifts, we argue, trigger the need to regard human and machine roles in communication processes in a more egalitarian fashion. Integrating anthropocentric and technocentric perspectives on communication, we propose an agent-agnostic framework for human-machine communication. This framework rejects exclusive assignment of communicative roles (sender, message, channel, receiver) to traditionally held agents and instead focuses on evaluating agents according to their functions as a means for considering what roles are held in communication processes. As a first step in advancing this agent-agnostic perspective, this theoretical paper offers three potential criteria that both humans and machines could satisfy: agency, interactivity, and influence. Future research should extend our agent-agnostic framework to ensure that communication theory will be prepared to deal with an ostensibly machine-inclusive future

El panorama de la industria 4.0 en el marco de la formación profesional del talento humano en salud

En la primera parte de este escrito se aborda el concepto de cuarta revolución industrial y la forma en la surge en Alemania, como una iniciativa estratégica de Gobierno en el año de 2011, la cual representa un paso de una sociedad industrial hacia una sociedad del conocimiento surgida desde en una revolución de orden digital, integrando Cyber-Physical Systems (CPS) para el desarrollo de espacios ciberfísicos que les permita optimizar los procesos industriales en entornos complejos, donde se genera creación, procesamiento, y análisis de datos en grandes cantidades dirigido a la toma de decisiones basadas en los conocimientos surgidos de esos análisis. En este entorno la producción dirigida a los individuos es fundamental, los productos se hacen de forma personalizada incluyendo los materiales, procesos y destinatario final. En este marco la inclusión del uso eficiente de la energía es fundamental en la integración de los procesos productivos. Lo que se materializa en la creación de nuevos modelos de administración caracterizados por las decisiones basadas en el conocimiento, incluyendo la rapidez y eficiencia basada en el análisis y graficación de datos. La constitución de redes y clúster está llamada a hacer parte de la vida de las empresas, incluyendo la minimización de costos y cambios en la cadena de suministros. Ello representa un cambio significativo en la forma como el talento humano se debe vincular a un mundo laboral marcado por la alta tecnología con la herramienta de la creatividad: se pasa del trabajador operario al trabajador creativo. En su conjunto se puede afirmar que los pilares de la Revolución 4.0 se encuentran soportados bajo la idea de ecosistema, donde se dan complejas relaciones entre los sistemas que la integran.En la segunda parte se abordan algunas aplicaciones de esta revolución al área de la salud como lo son la inteligencia artificial, Blockchain, internet de la salud, impresión 3D, robótica y realidad mixta. Finalmente en la tercera parte se realiza una descripción de la forma cómo se prevé el horizonte de posibilidades para los técnicos en salud en el marco de la cuarta revolución industrial para Latinoamérica, incluyendo una lectura del BID y se ofrece una presentación del tema desde un estudio de brechas realizado por la Cámara de comercio de Bogotá, PNUD y SENA, sobre brechas de capital humano en salud, desde el Clúster de salud de Bogotá-Región. Finalmente se cierra la reflexión con la presentación de las Habilidades para el trabajo futuro propuestas por el Institute for the Future for the University of Phoenix Research Institute. Objetivo: Generar una reflexión sobre el concepto de la cuarta revolución industrial y algunas aplicaciones en el área de la salud. Método: Se realizó una revisión bibliográfica de los temas abordados como marco general de la reflexión y posteriormente una propuesta reflexiva sobre algunos avances dentro del área de salud en el marco de esta revolución. Conclusiones: La Industria 4.0 genera grandes transformación en la forma como las empresas son administradas y la forma como producen, ya que la integración horizontal eje central de la integración, no sólo permite integrar los procesos de cada una de las áreas, sino que permite integrar los procesos de producción entre empresas con el fin de reducir costos y alcanzar unos mayores niveles de productividad y un mayor crecimiento económico para los países

Continuum Mechanical Models for Design and Characterization of Soft Robots

The emergence of ``soft'' robots, whose bodies are made from stretchable materials, has fundamentally changed the way we design and construct robotic systems. Demonstrations and research show that soft robotic systems can be useful in rehabilitation, medical devices, agriculture, manufacturing and home assistance. Increasing need for collaborative, safe robotic devices have combined with technological advances to create a compelling development landscape for soft robots. However, soft robots are not yet present in medical and rehabilitative devices, agriculture, our homes, and many other human-collaborative and human-interactive applications. This gap between promise and practical implementation exists because foundational theories and techniques that exist in rigid robotics have not yet been developed for soft robots. Theories in traditional robotics rely on rigid body displacements via discrete joints and discrete actuators, while in soft robots, kinematic and actuation functions are blended, leading to nonlinear, continuous deformations rather than rigid body motion. This dissertation addresses the need for foundational techniques using continuum mechanics. Three core questions regarding the use of continuum mechanical models in soft robotics are explored: (1) whether or not continuum mechanical models can describe existing soft actuators, (2) which physical phenomena need to be incorporated into continuum mechanical models for their use in a soft robotics context, and (3) how understanding on continuum mechanical phenomena may form bases for novel soft robot architectures. Theoretical modeling, experimentation, and design prototyping tools are used to explore Fiber-Reinforced Elastomeric Enclosures (FREEs), an often-used soft actuator, and to develop novel soft robot architectures based on auxetic behavior. This dissertation develops a continuum mechanical model for end loading on FREEs. This model connects a FREE’s actuation pressure and kinematic configuration to its end loads by considering stiffness of its elastomer and fiber reinforcement. The model is validated against a large experimental data set and compared to other FREE models used by roboticists. It is shown that the model can describe the FREE’s loading in a generalizable manner, but that it is bounded in its peak performance. Such a model can provide the novel function of evaluating the performance of FREE designs under high loading without the costs of building and testing prototypes. This dissertation further explores the influence viscoelasticity, an inherent property of soft polymers, on end loading of FREEs. The viscoelastic model developed can inform soft roboticists wishing to exploit or avoid hysteresis and force reversal. The final section of the dissertations explores two contrasting styles of auxetic metamaterials for their uses in soft robotic actuation. The first metamaterial architecture is composed of beams with distributed compliance, which are placed antagonistic configurations on a variety of surfaces, giving ride to shape morphing behavior. The second metamaterial architecture studied is a ``kirigami’’ sheet with an orthogonal cut pattern, utilizing lumped compliance and strain hardening to permanently deploy from a compact shape to a functional one. This dissertation lays the foundation for design of soft robots by robust physical models, reducing the need for physical prototypes and trial-and-error approaches. The work presented provides tools for systematic exploration of FREEs under loading in a wide range of configurations. The work further develops new concepts for soft actuators based on continuum mechanical modeling of auxetic metamaterials. The work presented expands the available tools for design and development of soft robotic systems, and the available architectures for soft robot actuation.PHDMechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163236/1/asedal_1.pd