Soft bioreactor systems: a necessary step toward engineered MSK soft tissue?

A key objective of tissue engineering (TE) is to produce in vitro funcional grafts that can replace damaged tissues or organs in patients. TE uses bioreactors, which are controlled environments, allowing the application of physical and biochemical cues to relevant cells growing in biomaterials. For soft musculoskeletal (MSK) tissues such as tendons, ligaments and cartilage, it is now well established that applied mechanical stresses can be incorporated into those bioreactor systems to support tissue growth and maturation via activation of mechanotransduction pathways. However, mechanical stresses applied in the laboratory are often oversimplified compared to those found physiologically and may be a factor in the slow progression of engineered MSK grafts towards the clinic. In recent years, an increasing number of studies have focused on the application of complex loading conditions, applying stresses of different types and direction on tissue constructs, in order to better mimic the cellular environment experienced in vivo. Such studies have highlighted the need to improve upon traditional rigid bioreactors, which are often limited to uniaxial loading, to apply physiologically relevant multiaxial stresses and elucidate their influence on tissue maturation. To address this need, soft bioreactors have emerged. They employ one or more soft components, such as flexible soft chambers that can twist and bend with actuation, soft compliant actuators that can bend with the construct, and soft sensors which record measurements in situ. This review examines types of traditional rigid bioreactors and their shortcomings, and highlights recent advances of soft bioreactors in MSK TE. Challenges and future applications of such systems are discussed, drawing attention to the exciting prospect of these platforms and their ability to aid development of functional soft tissue engineered grafts

Revolutionizing digital healthcare networks with wearable strain sensors using sustainable fibers

Wearable strain sensors have attracted research interest owing to their potential within digital healthcare, offering smarter tracking, efficient diagnostics, and lower costs. Unlike rigid sensors, fiber‐based ones compete with their flexibility, durability, adaptability to body structures as well as eco‐friendliness to environment. Here, the sustainable fiber‐based wearable strain sensors for digital health are reviewed, and material, fabrication, and practical healthcare aspects are explored. Typical strain sensors predicated on various sensing modalities, be it resistive, capacitive, piezoelectric, or triboelectric, are explained and analyzed according to their strengths and weaknesses toward fabrication and applications. The applications in digital healthcare spanning from body area sensing networks, intelligent health management, and medical rehabilitation to multifunctional healthcare systems are also evaluated. Moreover, to create a more complete digital health network, wired and wireless methods of data collection and examples of machine learning are elaborated in detail. Finally, the prevailing challenges and prospective insights into the advancement of novel fibers, enhancement of sensing precision and wearability, and the establishment of seamlessly integrated systems are critically summarized and offered. This endeavor not only encapsulates the present landscape but also lays the foundation for future breakthroughs in fiber‐based wearable strain sensor technology within the domain of digital health

Wireless Monitoring of Small Strains in Intelligent Robots via a Joule Heating Effect in Stretchable Graphene–Polymer Nanocomposites

Flexible strain sensors are an important component for future intelligent robotics. However, the majority of current strain sensors must be electrically connected to a corresponding monitoring system via conducting wires, which increases system complexity and restricts the working environment for monitoring strains. Here, stretchable graphene–polymer nanocomposites that act as strain sensors using a Joule heating effect are reported. When the resistance of the sensor changes in response to a strain, the resulting change in temperature is wirelessly detected in an intelligent robot. By engineering and optimizing the surface structure of graphene–polymer nanocomposites, the fabricated strain sensors exhibit excellent stability when subjected to periodic temperature signals over 400 cycles while being periodically strained and deliver a high strain sensitivity of 7.03 × 10−4 °C−1 %−1 for strain levels of 0% to 30%. As a wearable electronic device, the approach provides the capability to wirelessly monitor small strains for intelligent robots at a high strain resolution of ≈0.1%. Moreover, when the strain sensing system operates as a multichannel structure, it allows precise strain detection simultaneously, or in sequence, for each finger of an intelligent robot.</p

Micro-patterned graphene-based sensing skins for human physiological monitoring.

Ultrathin, flexible, conformal, and skin-like electronic transducers are emerging as promising candidates for noninvasive and nonintrusive human health monitoring. In this work, a wearable sensing membrane is developed by patterning a graphene-based solution onto ultrathin medical tape, which can then be attached to the skin for monitoring human physiological parameters and physical activity. Here, the sensor is validated for monitoring finger bending/movements and for recognizing hand motion patterns, thereby demonstrating its future potential for evaluating athletic performance, physical therapy, and designing next-generation human-machine interfaces. Furthermore, this study also quantifies the sensor's ability to monitor eye blinking and radial pulse in real-time, which can find broader applications for the healthcare sector. Overall, the printed graphene-based sensing skin is highly conformable, flexible, lightweight, nonintrusive, mechanically robust, and is characterized by high strain sensitivity

Soft Embedded Sensors with Learning-based Calibration for Soft Robotics

In this thesis, a new class of soft embedded sensors was conceptualized and three novel sensors were designed, fabricated, and tested for small force range soft robotic applications. The proposed soft sensors were consisted of a gelatin-graphite composite with piezoresistive characteristics. Principally, the sensing elements of the proposed class of soft sensors were moldable into any shape and size; thus, were embeddable and scalable. The sensing elements were directly molded into soft flexural structures so as to be embedded in the flexures. For each sensor, first a mechano-electrical phenomenological model for the exhibited piezoresistivity was proposed and validated experimentally. Afterwards, the sensors were subjected to a series of external forces to obtain calibration data. Given the complexity of the piezoresistivity and intrinsic large deformation of the soft bodies and sensing element, learning-based calibration approach were investigated. To compensate for ratedependency and hysteresis effects on sensor readings in calibration, rate-dependent features were selected for learning-based calibrations. Consequently, the first sensor of this research, i.e., one degree-of-freedom (1-DoF) force sensor, exhibited a force range of 0.035-0.82 N force measurement range with a mean-absolute-error (MAE) of 3.7% and a resolution of 4% of full-range. The second sensor, i.e., 3-DoF had a measurement range of up to 0.3 N with an MAE of 0.005 N and a resolution of 0.003 N. The third sensor, 6-DoF force-torque sensor, had a force range of up to 110 mN with an MAE of 7.4±6.5 mN and resolution of 1 mN and a torque range of 6.8 mNm with an MAE of 0.24 mNm. Comparison with the state-of-the-art and functional requirements of intraluminal procedures showed that the the proposed sensors were fairly compatible with the requirement and showed improvement of the state of the art. The major contribution of this research was to propose a scalable sensing principle that could adapt its shape to the shape of the host body, e.g., flexural robots. Moreover, this research showed nonlinear learning-based calibration is a fitting solution to overcome limitations of the state-of-the-art in using soft elastomeric sensors

DEVELOPMENT OF A NANOCOMPOSITE SENSOR AND ELECTRONIC SYSTEM FOR MONITORING OF LOCOMOTION OF A SOFT EARTHWORM ROBOT

The ability to detect external stimuli and perceive the surrounding areas represents a key feature of modern soft robotic systems, used for exploration of harsh environments. Although people have developed various types of biomimetic soft robots, no integratedsensor system is available to provide feedback locomotion. Here, a stretchable nanocomposite strain sensor with integrated wireless electronics to provide a feedbackloop locomotion of a soft robotic earthworm is presented. The ultrathin and soft strain sensor based on a carbon nanomaterial and a low-modulus silicone elastomer allows for a seamless integration with the body of the soft robot, accommodating large strains derived from bending, stretching, and physical interactions with obstacles. A scalable, costeffective, screen-printing method manufactures an array of strain sensors that are conductive and stretchable over 100% with a gauge factor over 38. An array of stretchable nanomembrane interconnectors enables a reliable connection between soft strain sensors and wireless electronics, while tolerating the robot’s multi-modal movements. A set of computational and experimental studies of soft materials, stretchable mechanics, and hybrid packaging provides key design factors for a reliable, nanocomposite sensor system. The miniaturized wireless circuit, embedded in the robot joint, offers a real-time monitoring of strain changes on the earthworm skin. Collectively, the soft sensor system shows a great potential to be integrated with other flexible, stretchable electronics for applications in soft robotics, wearable devices, and human-machine interfaces.M.S

Theoretical analysis and simulations applied to rational design strategies of nanostructured materials

Orientador: Douglas Soares GalvãoTese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb WataghinResumo: Esse documento apresenta uma coleção de trabalhos realizados dentro do amplo campo de materiais nanoestruturados, focando-se em descrições teóricas analíticas e simulações computacionais de diversos novos materias desse tipo. Uma nova fibra supereslástica e condutora é reportada. Essa fibra altamente esticável (até 1320%) é criada envolvendo-se um núcleo cilíndrico de borracha com uma camada de folha de nanotubos de carbono. O material resultante exibe uma interessante estrutura de enrugamentos hierárquicos na sua superfície, o que lhe garante propriedades elétricas úteis como conservar a sua resistencia constante enquanto esticada. Adicionando-se mais camadas de borracha ou nanotubos podemos obter aplicações como sensores de movimento ou deformação, atuadores/músculos artificiais ativados por corrente ou temperatura e operados reversivelmente por um mecanismo de acoplamento entre tensão e torção. Nós explicamos suas propriedades de condução elétrica e os fenômenos físicos envolvidos em cada uma dessas aplicações. Também desenvolvemos um novo método para o desenho racional de polímeros molecularmente impressos usando dinâmica molecular para simular o processo de impressão molecular e a análise subsequente utilizando experimentos de cromatografia simulada. Obtivemos com sucesso a primeira evidência teórica do mecanismo de impressão exibindo afinidade e seletividade para a substância alvo 17-beta-estradiol. Desenhamos e simulamos uma nova estrutura com formato de piramide em kirigami de grafeno, composta de uma folha de grafeno cortada em um padrão específico a fim de formar uma pirâmide quando sofre tensão na direção normal ao plano. Nós calculamos a resposta dessa estrutura a uma carga estática, quando ela age como uma mola de proporções nanométriacs. Também, utilizando simulações de dinâmica molecular de colisões balísticas, constatamos que a resistência desse material a impactos é ainda maior que de uma folha de grafeno puro, sendo ainda mais leve. Um novo método de reforçar fios de nanotubos de carbono, chamado ITAP, também é reportado. Esse método foi capaz de melhorar a resistencia mecanica do fio em até 1,5 vezes e torná-lo muito mais resistente ao ataque de ácido quando comparado com um fio não tratado. Utilizamos simulações de dinâmica molecular para testar a hipótese de que esse tratamento é suficiente para gerar ligações covalentes entre as paredes externas de nanotubos diferentes, o que seria responsável pelas propriedades do material. Aplicamos um algoritmo genético modificado ao problema do folding de proteínas em um modelo de rede 3D HP. Testamos o algoritmo utilizando um conjunto de sequencias de teste que têm estado em uso pelos últimos 20 anos na literatura. Fomos capazes de melhorar um dos resultados e demonstramos a aplicação e utilidade de operadores não canônicos que evitam a convergência prematura do algoritmo, sendo eles o operador de compartilhamento e efeito maternalAbstract: This document presents a colection of works done within the broad subject of nano-structured materials, focusing on analytical theoretical descriptions and computational simulations of new kinds of this class of materials. A new superelastic conducting fiber is reported, with improved properties and functionalities. They are highly stretchable (up to 1320%) conducting fibers created by wrapping carbon nanotube sheets on stretched rubber fiber cores. The resulting structure exhibited an interesting hierarchical buckled structure on its surface. By including more rubber and carbon nanotube layers, we created strain sensors, and electrically or thermally powered tensile and torsional muscles/actuators operating reversibly by a coupled tension-to-torsion actuation mechanism. We explain its electronic properties and quantitatively explain the compounded physical effects involved in each of these applications. We also developed a new method for the rational design of molecularly imprinted polymers using molecular dynamics to simulate the imprinting process and subsequent chromatography studies. We successfully obtained the first theoretical evidence of actual imprinting happening under unconstrained simulations showing affinity and selectivity to the target substance 17-beta estradiol. We designed and simulated a new graphene kirigami pyramid structure, composed of a cut graphene sheet in a specific pattern in order to form a pyramid when under stress perpendicular to the plane. We calculated the response to static loading of this structure that acts like a nano-sized spring. Also, with simulated ballistic collisions we obtained increased resistance to impact in comparison with a pure graphene sheet. A new method of strengthening carbon nanotube yarns, called ITAP, consisting of annealing at high temperature in vacuum is reported. This method is shown to increase the mechanical resistance of the wire up to 1.5 times and make it much more resistant to acid corrosion when compared to pristine non-treated wires. We applied a modified genetic algorithm to the protein folding problem using an 3D HP lattice model using known test sequences that have been in use for the last 20 years and obtained an improvement for the best solution found for one of these proteins. Also, the importance of new non-canonical operators that prevent rapid convergence of the algorithm was demonstrated, namely the Sharing and Maternal Effect operatorsDoutoradoFísicaDoutor em Ciências141198/2012-5CNP