image-guided-vivo-tracking-transplanted-distal-lung-epithelial

Image-guided <em>In Vivo</em> Tracking of Transplanted Distal Lung Epithelial Progenitor Cells for Pulmonary Fibrosis Using Magnetic Particle Imaging

Pulmonary fibrosis (PF) is a progressive and chronic lung disease characterized by repeated alveolar epithelial injury that leads to excessive ...

Michigan State University

Small soft robotic systems are being explored for myriad applications in medicine. Specifically, magnetically actuated microrobots capable of remote manipulation hold significant potential for the targeted delivery of therapeutics and biologicals. Much of previous efforts on microrobotics have been dedicated to locomotion in aqueous environments and hard surfaces. However, our human bodies are made of dense biological tissues, requiring researchers to develop new microrobotics that can locomote atop tissue surfaces. Tumbling microrobots are a sub-category of these devices capable of walking on surfaces guided by rotating magnetic fields. Using microrobots to deliver payloads to specific regions of sensitive tissues is a primary goal of medical microrobots. Central nervous system (CNS) tissues are a prime candidate given their delicate structure and highly region-specific function. Here we demonstrate surface walking of soft alginate capsules capable of moving on top of a rat cortex and mouse spinal cord , demonstrating multi-location small molecule delivery to up to six different locations on each type of tissue with high spatial specificity. The softness of alginate gel prevents injuries that may arise from friction with CNS tissues during millirobot locomotion. Development of this technology may be useful in clinical and preclinical applications such as drug delivery, neural stimulation, and diagnostic imaging.

Soft Capsule Magnetic Millirobots for Region-Specific Drug Delivery in the Central Nervous System.

For colorectal cancer patients, traditional biomarker deficient mismatch repair/microsatellite instability (dMMR/MSI) is an accurate predictor of immune checkpoint inhibitors (ICIs). Recent years, researchers considered tumor mutation burden (TMB) as another predictive biomarker which means the number of nonsynonymous mutations in cancer cells. Several studies have proven that TMB can evaluate the efficacy of ICI therapy in diverse types of cancer, especially in non-small cell lung cancer and melanoma. However, studies on the association between TMB and the response to ICI therapy in colorectal cancer alone are still lacking. In this study, we aim to verify the effect of TMB as a biomarker in predicting the efficacy of ICIs in colorectal cancer.

Tumor Mutational Burden Predicting the Efficacy of Immune Checkpoint Inhibitors in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

A tissue-like neurotransmitter sensor for the brain and gut.

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.

Technology Roadmap for Flexible Sensors.

Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19) has shown extensive lung manifestations in vulnerable individuals, putting lung imaging and monitoring at the forefront of early detection and treatment. Magnetic particle imaging (MPI) is an imaging modality, which can bring excellent contrast, sensitivity, and signal-to-noise ratios to lung imaging for the development of new theranostic approaches for respiratory diseases. Advances in MPI tracers would offer additional improvements and increase the potential for clinical translation of MPI. Here, a high-performance nanotracer based on shape anisotropy of magnetic nanoparticles is developed and its use in MPI imaging of the lung is demonstrated. Shape anisotropy proves to be a critical parameter for increasing signal intensity and resolution and exceeding those properties of conventional spherical nanoparticles. The 0D nanoparticles exhibit a 2-fold increase, while the 1D nanorods have a > 5-fold increase in signal intensity when compared to VivoTrax. Newly designed 1D nanorods displayed high signal intensities and excellent resolution in lung images. A spatiotemporal lung imaging study in mice revealed that this tracer offers new opportunities for monitoring disease and guiding intervention.

Shape Anisotropy-Governed High-Performance Nanomagnetosol for In Vivo Magnetic Particle Imaging of Lungs.

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, ‶spiral transformation″, to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.

Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation.

Molecular intelligent perception on soft interfaces.

Freezing of gait (FOG) is a disabling yet poorly understood paroxysmal gait disorder affecting the vast majority of patients with Parkinson's disease (PD) as they reach advanced stages of the disorder. Falling is one of the most disabling consequences of a FOG episode; it often results in injury and a future fear of falling, leading to diminished social engagement, a reduction in general fitness, loss of independence, and degradation of overall quality of life. Currently, there is no robust or reliable treatment against FOG in PD. In the absence of reliable and effective treatment for Parkinson's disease, alleviating the consequences of FOG represents an unmet clinical need, with the first step being reliable FOG prediction. Current methods for FOG prediction and prevention cannot provide real-time readouts and are not sensitive enough to detect changes in walking patterns or balance. To fill this gap, we developed an sEMG system consisting of a soft, wearable garment (pair of shorts and two calf sleeves) embedded with screen-printed electrodes and stretchable traces capable of picking up and recording the electromyography activities from lower limb muscles. Here, we report on the testing of these garments in healthy individuals and in patients with PD FOG. The preliminary testing produced an initial time-to-onset commencement that persisted > 3 s across all patients, resulting in a nearly 3-fold drop in sEMG activity. We believe that these initial studies serve as a solid foundation for further development of smart digital textiles with integrated bio and chemical sensors that will provide AI-enabled, medically oriented data.

Wearable Surface Electromyography System to Predict Freeze of Gait in Parkinson's Disease Patients.

Separators are critical components in lithium-ion batteries (LIBs), preventing internal short circuits, mitigating thermal runaway, and influencing rate capability and cycling performance. However, current polyolefin separators suffer from limitations, such as high thermal shrinkage, relatively poor wettability, and inadequate long-term stability, impacting safety and cycle life in critical applications like electric vehicles. Here, a single-layer lignin-based ultrathin separator (as thin as 15 µm) with exceptional intrinsic thermal stability and cycling performance is demonstrated. The separator is fabricated using lignosulfonate, a natural polymer derived as a byproduct of chemical pulping and biorefinery processes. By employing a dry fibrillation method, the process achieves low energy consumption and a 100% raw material conversion rate, highlighting its scalability and sustainability. Interfacial studies reveal the improved cycling performance in both graphite||NMC811 and Si-Gr||NMC811 cells is attributed to the abundant sulfonate functional groups in lignosulfonates, which promote the formation of a sulfur-rich cathode/solid electrolyte interphases (CEI/SEI) with low resistance in both the cathode and anode. The high thermal stability, manufacturing feasibility, battery performance, and low cost of such lignin-based separators offer new inspiration for developing next-generation, single-layer functional separators tailored for high-performance LIBs.

Lignin-Based Separators for Lithium-Ion Batteries via a Dry Fibrillation Method.

Nature's ability to create complex and functionalized organisms has long inspired engineers and scientists to develop increasingly advanced machines. Magnetotactic bacteria (MTB), a group of Gram-negative prokaryotes that biomineralize iron and thrive in aquatic environments, have garnered significant attention from the bioengineering community. These bacteria possess chains of magnetic nanocrystals known as magnetosomes, which allow them to align with Earth's geomagnetic field and navigate through aquatic environments via magnetotaxis, enabling localization to areas rich in nutrients and optimal oxygen concentration. Their built-in magnetic components, along with their intrinsic and/or modified biological functions, make them one of the most promising platforms for future medical microrobots. Leveraging an externally applied magnetic field, the motion of MTBs can be precisely controlled, rendering them suitable for use as a new type of biohybrid microrobotics with great promise in medicine for bioimaging, drug delivery, cancer therapy, antimicrobial treatment, and detoxification. This mini-review provides an up-to-date overview of recent advancements in MTB microrobots, delineates the interaction between MTB microrobots and magnetic fields, elucidates propulsion mechanisms and motion control, and reports state-of-the-art strategies for modifying and functionalizing MTB for medical applications.

Engineering Magnetotactic Bacteria as Medical Microrobots.

Inspired by Richard Feynman's 1959 lecture and the 1966 film , the field of micro/nanorobots has evolved from science fiction to reality, with significant advancements in biomedical and environmental applications. Despite the rapid progress, the deployment of functional micro/nanorobots remains limited. This review of the technology roadmap identifies key challenges hindering their widespread use, focusing on propulsion mechanisms, fundamental theoretical aspects, collective behavior, material design, and embodied intelligence. We explore the current state of micro/nanorobot technology, with an emphasis on applications in biomedicine, environmental remediation, analytical sensing, and other industrial technological aspects. Additionally, we analyze issues related to scaling up production, commercialization, and regulatory frameworks that are crucial for transitioning from research to practical applications. We also emphasize the need for interdisciplinary collaboration to address both technical and nontechnical challenges, such as sustainability, ethics, and business considerations. Finally, we propose a roadmap for future research to accelerate the development of micro/nanorobots, positioning them as essential tools for addressing grand challenges and enhancing the quality of life.

Article	Year
Soft Capsule Magnetic Millirobots for Region-Specific Drug Delivery in the Central Nervous System. Frontiers in robotics and AI\| PubMed ID: 34368238	2021
Tumor Mutational Burden Predicting the Efficacy of Immune Checkpoint Inhibitors in Colorectal Cancer: A Systematic Review and Meta-Analysis. Frontiers in immunology\| PubMed ID: 34659255	2021
A tissue-like neurotransmitter sensor for the brain and gut. Nature\| PubMed ID: 35650358	2022
Technology Roadmap for Flexible Sensors. ACS nano\| PubMed ID: 36892156	2023
Shape Anisotropy-Governed High-Performance Nanomagnetosol for In Vivo Magnetic Particle Imaging of Lungs. Small (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 37735143	2024
Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation. bioRxiv : the preprint server for biology\| PubMed ID: 37873341	2023
Molecular intelligent perception on soft interfaces. Science bulletin\| PubMed ID: 38238206	2024
Wearable Surface Electromyography System to Predict Freeze of Gait in Parkinson's Disease Patients. Sensors (Basel, Switzerland)\| PubMed ID: 39686390	2024
Lignin-Based Separators for Lithium-Ion Batteries via a Dry Fibrillation Method. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 40134365	2025
Engineering Magnetotactic Bacteria as Medical Microrobots. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 40244080	2025
Technology Roadmap of Micro/Nanorobots. ACS nano\| PubMed ID: 40577644	2025

Jinxing Li

Biography

JoVE Journal Publications

Other Publications