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The ability to model physiological systems through 3D neural in-vitro systems may enable new treatments for various diseases while lowering the need for challenging animal and human testing. Creating such an environment, and even more impactful, one that mimics human brain tissue under mechanical stimulation, would be extremely useful to study a range of human-specific biological processes and conditions related to brain trauma. One approach is to use human cerebral organoids (hCOs) in-vitro models. hCOs recreate key cytoarchitectural features of the human brain, distinguishing themselves from more traditional 2D cultures and organ-on-a-chip models, as well as in-vivo animal models. Here, we propose a novel approach to emulate mild and moderate traumatic brain injury (TBI) using hCOs that undergo strain rates indicative of TBI. We subjected the hCOs to mild (2 s⁻¹) and moderate (14 s⁻¹) loading conditions, examined the mechanotransduction response, and investigated downstream genomic effects and regulatory pathways. The revealed pathways of note were cell death and metabolic and biosynthetic pathways implicating genes such as CARD9, ENO1, and FOXP3, respectively. Additionally, we show a steeper ascent in calcium signaling as we imposed higher loading conditions on the organoids. The elucidation of neural response to mechanical stimulation in reliable human cerebral organoid models gives insights into a better understanding of TBI in humans.

 

Physically soft magnetic materials (PSMMs) represent an emerging class of materials that can change shape or rheology in response to an external magnetic field. However, until now, no studies have investigated using an electropermanent magnet (EPM) and magnetic repulsion to magnetically deform PSMMs. Such capabilities would enable the ability to deform PSMMs without the need for continuous electrical input and produce PSMM film deformation without an air gap, as would be required with magnetic attraction. To address this, we introduce a PSMM-EPM architecture in which the shape of a soft deformable thin film is controlled by switching between bistable on/off states of the EPM circuit. We characterized the deflection of a PSMM thin film when placed at controlled distances normal to the surface of the EPM and compared its response for cases when the EPM is in the ‘on’ and ‘off’ states. This work is the first to demonstrate a magnetically repelled soft deformable thin film that achieves two electronically-controlled modes of deformation through the on and off states of an EPM. This work has the potential to advance the development of new magneto-responsive soft materials and systems.

 

Liquid metal embedded elastomers (LMEEs) are highly stretchable composites comprising microscopic droplets of eutectic gallium‐indium (EGaIn) liquid metal embedded in a soft rubber matrix. They have a unique combination of mechanical, electrical, and thermal properties that make them attractive for potential applications in flexible electronics, thermal management, wearable computing, and soft robotics. However, the use of LMEEs in direct contact with human tissue or organs requires an understanding of their biocompatibility and cell cytotoxicity. In this study, the cytotoxicity of C2C12 cells in contact with LMEE composites composed of EGaIn droplets embedded with a polydimethylsiloxane (PDMS) matrix is investigated. In particular, the influence of EGaIn volume ratio and shear mixing time during synthesis on cell proliferation and viability is examined. The special case of electrically‐conductive LMEE composites in which a percolating network of EGaIn droplets is created through “mechanical sintering” is also examined. This study in C2C12 cytotoxicity represents a first step in determining whether LMEE is safe for use in implantable biomedical devices and biohybrid systems.

 

Successful surgical operations are characterized by preplanning routines to be executed during actual surgical operations. To achieve this, surgeons rely on the experience acquired from the use of cadavers, enabling technologies like virtual reality (VR) and clinical years of practice. However, cadavers, having no dynamism and realism as they lack blood, can exhibit limited tissue degradation and shrinkage, while current VR systems do not provide amplified haptic feedback. This can impact surgical training increasing the likelihood of medical errors. This work proposes a novel Mixed Reality Combination System (MRCS) that pairs Augmented Reality (AR) technology and an inertial measurement unit (IMU) sensor with 3D printed, collagen-based specimens that can enhance task performance like planning and execution. To achieve this, the MRCS charts out a path prior to a user task execution based on a visual, physical, and dynamic environment on the state of a target object by utilizing surgeon-created virtual imagery that, when projected onto a 3D printed biospecimen as AR, reacts visually to user input on its actual physical state. This allows a real-time user reaction of the MRCS by displaying new multi-sensory virtual states of an object prior to performing on the actual physical state of that same object enabling effective task planning. Tracked user actions using an integrated 9-Degree of Freedom IMU demonstrate task execution This demonstrates that a user, with limited knowledge of specific anatomy, can, under guidance, execute a preplanned task. In addition, to surgical planning, this system can be generally applied in areas such as construction, maintenance, and education.

 

The evolution of tissue on a chip systems holds promise for mimicking the response of biological functionality of physiological systems. One important direction for tissue on a chip approaches are neuron‐based systems that could mimic neurological responses and lessen the need for in vivo experimentation. For neural research, more attention has been devoted recently to understanding mechanics due to issues in areas such as traumatic brain injury (TBI) and pain, among others. To begin to address these areas, a 3D Nerve Integrated Tissue on a Chip (NITC) approach combined with a Mechanical Excitation Testbed (MET) System is developed to impose external mechanical stimulation toward more realistic physiological environments. PC12 cells differentiated with nerve growth factor, which were cultured in a controlled 3D scaffolds, are used. The cells are labeled in a 3D NITC system with Fluo‐4‐AM to examine their calcium response under mechanical stimulation synchronized with image capture. Understanding the neural responses to mechanical stimulation beyond 2D systems is very important for neurological studies and future personalized strategies. This work will have implications in a diversity of areas including tissue‐on‐a‐chip systems, biomaterials, and neuromechanics.

 

The communication between different cell populations is an important aspect of many natural phenomena that can be studied with microfluidics. Using microfluidic valves, these complex interactions can be studied with a higher level of control by placing a valve between physically separated populations. However, most current valve designs do not display the properties necessary for this type of system, such as providing variable flow rate when embedded inside a microfluidic device. While some valves have been shown to have such tunable behavior, they have not been used for dynamic, real-time outputs. We present an electric solenoid valve that can be fabricated completely outside of a cleanroom and placed into any microfluidic device to offer control of dynamic fluid flow rates and profiles. After characterizing the behavior of this valve under controlled test conditions, we developed a regression model to determine the required input electrical signal to provide the solenoid the ability to create a desired flow profile. With this model, we demonstrated that the valve could be controlled to replicate a desired, time-varying pattern for the interface position of a co-laminar fluid stream. Our approach can be performed by other investigators with their microfluidic devices to produce predictable, dynamic fluidic behavior. In addition to modulating fluid flows, this work will be impactful for controlling cellular communication between distinct populations or even chemical reactions occurring in microfluidic channels.

 

The transition from sessile suspension to active mobile detritus feeding in early echinoderms (c.a. 500 Mya) required sophisticated locomotion strategies. However, understanding locomotion adopted by extinct animals in the absence of trace fossils and modern analogues is extremely challenging. Here, we develop a biomimetic soft robot testbed with accompanying computational simulation to understand fundamental principles of locomotion in one of the most enigmatic mobile groups of early stalked echinoderms—pleurocystitids. We show that these Paleozoic echinoderms were likely able to move over the sea bottom by means of a muscular stem that pushed the animal forward (anteriorly). We also demonstrate that wide, sweeping gaits could have been the most effective for these echinoderms and that increasing stem length might have significantly increased velocity with minimal additional energy cost. The overall approach followed here, which we call “Paleobionics,” is a nascent but rapidly developing research agenda in which robots are designed based on extinct organisms to generate insights in engineering and evolution.

 

Abstract New microfluidic systems for whole organism analysis and experimentation are catalyzing biological breakthroughs across many fields, from human health to fundamental biology principles. This perspective discusses recent microfluidic tools to study intact model organisms to demonstrate the tremendous potential for these integrated approaches now and into the future. We describe these microsystems' technical features and highlight the unique advantages for precise manipulation in areas including immobilization, automated alignment, sorting, sensory, mechanical and chemical stimulation, and genetic and thermal perturbation. Our aim is to familiarize technologically focused researchers with microfluidics applications in biology research, while providing biologists an entrée to advanced microengineering techniques for model organisms.