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The vagus nerve (VN) plays an important role in regulating physiological conditions in the gastrointestinal (GI) tract by communicating via the parasympathetic pathway to the enteric nervous system (ENS). However, the lack of knowledge in the neurophysiology of the VN and GI tract limits the development of advanced treatments for autonomic dysfunctions related to the VN. To better understand the complicated underlying mechanisms of the VN-GI tract neurophysiology, it is necessary to use an advanced device enabled by microfabrication technologies. Among several candidates including intraneural probe array and extraneural cuff electrodes, microchannel electrode array devices can be used to interface with smaller numbers of nerve fibers by securing them in the separate channel structures. Previous microchannel electrode array devices to interface teased nerve structures are relatively bulky with thickness around 200 µm. The thick design can potentially harm the delicate tissue structures, including the nerve itself. In this paper, we present a flexible thin film based microchannel electrode array device (thickness: 11.5 µm) that can interface with one of the subdiaphragmatic nerve branches of the VN in a rat. We demonstrated recording evoked compound action potentials (ECAP) from a transected nerve ending that has multiple nerve fibers. Moreover, our analysis confirmed that the signals are from C-fibers that are critical in regulating autonomic neurophysiology in the GI tract.

 

Maintaining the patency of indwelling drainage devices is critical in preventing further complications following an intraventricular hemorrhage (IVH) and other chronic disease management. Surgeons often use drainage devices to remove blood and cerebrospinal fluid but these catheters frequently become occluded with hematoma. Using an implantable magnetic microactuator, we created a self-clearing catheter that can generate large enough forces to break down obstructive blood clots by applying time-varying magnetic fields. In a blood-circulating model, our self-clearing catheters demonstrated a > 7x longer functionality than traditional catheters (211 vs. 27 min) and maintained a low pressure for longer periods (239 vs. 79 min). Using a porcine IVH model, the self-clearing catheters showed a greater survival rate than control catheters (86% vs. 0%) over the course of 6 weeks. The treated animals also had significantly smaller ventricle sizes 1 week after implantation compared to the control animals with traditional catheters. Our results suggest that these magnetic microactuator-embedded smart catheters can expedite the removal of blood from the ventricles and potentially improve the outcomes of critical patients suffering from often deadly IVH.

 

The growing need for the implementation of stretchable biosensors in the body has driven rapid prototyping schemes through the direct ink writing of multidimensional functional architectures. Recent approaches employ biocompatible inks that are dispensable through an automated nozzle injection system. However, their application in medical practices remains challenged in reliable recording due to their viscoelastic nature that yields mechanical and electrical hysteresis under periodic large strains. Herein, we report sponge-like poroelastic silicone composites adaptable for high-precision direct writing of custom-designed stretchable biosensors, which are soft and insensitive to strains. Their unique structural properties yield a robust coupling to living tissues, enabling high-fidelity recording of spatiotemporal electrophysiological activity and real-time ultrasound imaging for visual feedback. In vivo evaluations of custom-fit biosensors in a murine acute myocardial infarction model demonstrate a potential clinical utility in the simultaneous intraoperative recording and imaging on the epicardium, which may guide definitive surgical treatments.

 

The global cost of diabetes care exceeds $1 trillion each year with more than $327 billion being spent in the United States alone. Despite some of the advances in diabetes care including continuous glucose monitoring systems and insulin pumps, the technology associated with managing diabetes has largely remained unchanged over the past several decades. With the rise of wearable electronics and novel functional materials, the field is well‐poised for the next generation of closed‐loop diabetes care. Wearable glucose sensors implanted within diverse platforms including skin or on‐tooth tattoos, skin‐mounted patches, eyeglasses, contact lenses, fabrics, mouthguards, and pacifiers have enabled noninvasive, unobtrusive, and real‐time analysis of glucose excursions in ambulatory care settings. These wearable glucose sensors can be integrated with implantable drug delivery systems, including an insulin pump, glucose responsive insulin release implant, and islets transplantation, to form self‐regulating closed‐loop systems. This review article encompasses the emerging trends and latest innovations of wearable glucose monitoring and implantable insulin delivery technologies for diabetes management with a focus on their advanced materials and construction. Perspectives on the current unmet challenges of these strategies are also discussed to motivate future technological development toward improved patient care in diabetes management.

 

Accurately replicating and analyzing cellular responses to mechanical cues is vital for exploring metastatic disease progression. However, many of the existing in vitro platforms for applying mechanical stimulation seed cells on synthetic substrates. To better recapitulate physiological conditions, a novel actuating platform is developed with the ability to apply tensile strain on cells at various amplitudes and frequencies in a high‐throughput multi‐well culture plate using a physiologically relevant substrate. Suspending fibrillar fibronectin across the body of the magnetic actuator provides a matrix representative of early metastasis for 3D cell culture that is not reliant on a synthetic substrate. This platform enables the culturing and analysis of various cell types in an environment that mimics the dynamic stretching of lung tissue during normal respiration. Metabolic activity, YAP activation, and morphology of breast cancer cells are analyzed within one week of cyclic stretching or static culture. Further, matrix degradation is significantly reduced in breast cancer cell lines with metastatic potential after actuation. These new findings demonstrate a clear suppressive cellular response due to cyclic stretching that has implications for a mechanical role in the dormancy and reactivation of disseminated breast cancer cells to macrometastases.

 

Worldwide, there are currently around 18.1 million new cancer cases and 9.6 million cancer deaths yearly. Although cancer diagnosis and treatment has improved greatly in the past several decades, a complete understanding of the complex interactions between cancer cells and the tumor microenvironment during primary tumor growth and metastatic expansion is still lacking. Several aspects of the metastatic cascade require in vitro investigation. This is because in vitro work allows for a reduced number of variables and an ability to gather real-time data of cell responses to precise stimuli, decoupling the complex environment surrounding in vivo experimentation. Breakthroughs in our understanding of cancer biology and mechanics through in vitro assays can lead to better-designed ex vivo precision medicine platforms and clinical therapeutics. Multiple techniques have been developed to imitate cancer cells in their primary or metastatic environments, such as spheroids in suspension, microfluidic systems, 3D bioprinting, and hydrogel embedding. Recently, magnetic-based in vitro platforms have been developed to improve the reproducibility of the cell geometries created, precisely move magnetized cell aggregates or fabricated scaffolding, and incorporate static or dynamic loading into the cell or its culture environment. Here, we will review the latest magnetic techniques utilized in these in vitro environments to improve our understanding of cancer cell interactions throughout the various stages of the metastatic cascade. 

To address a key challenge of conjugated polymers in biomedical applications having poor antifouling properties that eventually leads to the failure and reduced lifetime of bioelectronics in the body, herein we describe the design, synthesis, and evaluation of our newly designed multifunctional zwitterionic liquid crystalline polymer PCBTh-C8C10 , which is facilely synthesized using oxidative polymerization. A conjugated polythiophene backbone, a multifunctional zwitterionic side chain, and a mesogenic unit are integrated into one segment. By DSC and POM characterization, we verify that the introduction of 3,5-bis(2-octyl-1-dodecyloxy)benzene as a mesogenic unit into the polythiophene backbone allows the formation of the liquid crystalline mesophase of the resulting polymer. We also demonstrate that the PCBTh-C8C10 coated surface exhibits good conductivity, stability, hydrophilicity, and remarkable antibiofouling properties against protein adsorption, cell growth, and bacteria attachment. This new zwitterionic liquid crystalline polymer having good antibiofouling features will be widely recognized as a promising biomaterial that is applicable in implantable organic bioelectronics via inhibiting the foreign body response. A deep understanding of structure–property relationships of zwitterionic conjugated polymers has also been provided in this study. 

The growing trend for personalized medicine calls for more reliable implantable biosensors that are capable of continuously monitoring target analytes for extended periods (i.e., >30 d). While promising biosensors for various applications are constantly being developed in the laboratories across the world, many struggle to maintain reliable functionality in complex in vivo environments over time. In this review, we explore the impact of various biotic and abiotic failure modes on the reliability of implantable biosensors. We discuss various design considerations for the development of chronically reliable implantable biosensors with a specific focus on strategies to combat biofouling, which is a fundamental challenge for many implantable devices. Briefly, we introduce the process of the foreign body response and compare the in vitro and the in vivo performances of state-of-the-art implantable biosensors. We then discuss the latest development in material science to minimize and delay biofouling including the usage of various hydrophilic, biomimetic, drug-eluting, zwitterionic, and other smart polymer materials. We also explore a number of active anti-biofouling approaches including stimuli-responsive materials and mechanical actuation. Finally, we conclude this topical review with a discussion on future research opportunities towards more reliable implantable biosensors.