Magnetically Actuated Microscaffold with Controllable Magnetization and Morphology for Regeneration of Osteochondral Tissue.

Magnetic microscaffolds capable of targeted cell delivery have been developed for tissue regeneration. However, the microscaffolds developed so far with similar morphologies have limitations for applications to osteochondral disease, which requires simultaneous treatment of the cartilage and subchondral bone. This study proposes magnetically actuated microscaffolds tailored to the cartilage and subchondral bone for osteochondral tissue regeneration, named magnetically actuated microscaffolds for cartilage regeneration (MAM-CR) and for subchondral bone regeneration (MAM-SBR). The morphologies of the microscaffolds were controlled using a double emulsion and microfluidic flow. In addition, due to their different sizes, MAM-CR and MAM-SBR have different magnetizations because of the different amounts of magnetic nanoparticles attached to their surfaces. In terms of biocompatibility, both microscaffolds were shown to grow cells without toxicity as potential cell carriers. In magnetic actuation tests of the microscaffolds, the relatively larger MAM-SBR moved faster than the MAM-CR under the same magnetic field strength. In a feasibility test, the magnetic targeting of the microscaffolds in 3D knee cartilage phantoms showed that the MAM-SBR and MAM-CR were sequentially moved to the target sites. Thus, the proposed magnetically actuated microscaffolds provide noninvasive treatment for osteochondral tissue disease.

Wearable Localized Surface Plasmon Resonance-Based Biosensor with Highly Sensitive and Direct Detection of Cortisol in Human Sweat.

Wearable biosensors have the potential for developing individualized health evaluation and detection systems owing to their ability to provide continuous real-time physiological data. Among various wearable biosensors, localized surface plasmon resonance (LSPR)-based wearable sensors can be versatile in various practical applications owing to their sensitive interactions with specific analytes. Understanding and analyzing endocrine responses to stress is particularly crucial for evaluating human performance, diagnosing stress-related diseases, and monitoring mental health, as stress takes a serious toll on physiological health and psychological well-being. Cortisol is an essential biomarker of stress because of the close relationship between cortisol concentration in the human body and stress level. In this study, a flexible LSPR biosensor was manufactured to detect cortisol levels in the human body by depositing gold nanoparticle (AuNP) layers on a 3-aminopropyltriethoxysilane (APTES)-functionalized poly (dimethylsiloxane) (PDMS) substrate. Subsequently, an aptamer was immobilized on the surface of the LSPR substrate, enabling highly sensitive and selective cortisol capture owing to its specific cortisol recognition. The biosensor exhibited excellent detection ability in cortisol solutions of various concentrations ranging from 0.1 to 1000 nM with a detection limit of 0.1 nM. The flexible LSPR biosensor also demonstrated good stability under various mechanical deformations. Furthermore, the cortisol levels of the flexible LSPR biosensor were also measured in the human epidermis before and after exercise as well as in the morning and afternoon. Our biosensors, which combine easily manufactured flexible sensors with sensitive cortisol-detecting molecules to measure human stress levels, could be versatile candidates for human-friendly products.

Multifunctional microrobot with real-time visualization and magnetic resonance imaging for chemoembolization therapy of liver cancer.

Microrobots that can be precisely guided to target lesions have been studied for in vivo medical applications. However, existing microrobots have challenges in vivo such as biocompatibility, biodegradability, actuation module, and intra- and postoperative imaging. This study reports microrobots visualized with real-time x-ray and magnetic resonance imaging (MRI) that can be magnetically guided to tumor feeding vessels for transcatheter liver chemoembolization in vivo. The microrobots, composed of a hydrogel-enveloped porous structure and magnetic nanoparticles, enable targeted delivery of therapeutic and imaging agents via magnetic guidance from the actuation module under real-time x-ray imaging. In addition, the microrobots can be tracked using MRI as postoperative imaging and then slowly degrade over time. The in vivo validation of microrobot system-mediated chemoembolization was demonstrated in a rat liver with a tumor model. The proposed microrobot provides an advanced medical robotic platform that can overcome the limitations of existing microrobots and current liver chemoembolization.

Microrobot with Gyroid Surface and Gold Nanostar for High Drug Loading and Near-Infrared-Triggered Chemo-Photothermal Therapy.

The use of untethered microrobots for precise synergistic anticancer drug delivery and controlled release has attracted attention over the past decade. A high surface area of the microrobot is desirable to achieve greater therapeutic effect by increasing the drug load. Therefore, various nano- or microporous microrobot structures have been developed to load more drugs. However, as most porous structures are not interconnected deep inside, the drug-loading efficiency may be reduced. Here, we propose a magnetically guided helical microrobot with a Gyroid surface for high drug-loading efficiency and precise drug delivery. All spaces inside the proposed microrobot are interconnected, thereby enabling drug loading deep inside the structure. Moreover, we introduce gold nanostars on the microrobot structure for near-infrared-induced photothermal therapy and triggering drug release. The results of this study encourage further exploration of a high loading efficiency in cell-based therapeutics, such as stem cells or immune cells, for microrobot-based drug-delivery systems.

Shape-Tunable UV-Printed Solid Drugs for Personalized Medicine.

Several recent advances have emerged in biotherapy and the development of personal drugs. However, studies exploring effective manufacturing methods of personal drugs remain limited. In this study, solid drugs based on poly(ethylene glycol)diacrylate (PEGDA) hydrogel and doxorubicin were fabricated, and their final geometry was varied through UV-light patterning. The results suggested that the final drug concentration was affected by the geometrical volume as well as the UV-light exposure time. The analysis of PEGDA showed no effect on the surrounding cells, indicating its high biocompatibility. However, with the addition of doxorubicin, it showed an excellent therapeutic effect, indicating that drugs inside the PEGDA structure could be successfully released. This approach enables personal drugs to be fabricated in a simple, fast, and uniform manner, with perfectly tuned geometry.

Magnetically controlled reversible shape-morphing microrobots with real-time X-ray imaging for stomach cancer applications.

Stomach cancer is a global health concern as millions of cases are reported each year. In the present study, we developed a pH-responsive microrobot with good biocompatibility, magnetic-field controlled movements, and the ability to be visualized via X-ray imaging. The microrobot consisted of composite resin and a pH-responsive layer. This microrobot was found to fold itself in high pH environments and unfold itself in low pH environments. In addition, the neodymium (NdFeB) magnetic nanoparticles present inside the composite resin provided the microrobot with an ability to be controlled by a magnetic field through an electromagnetic actuation system, and the monomeric triiodobenzoate-based particles were found to act as contrast agents for real-time X-ray imaging. The doxorubicin coating on the microrobot's surface resulted in a high cancer-cell killing effect. Finally, we demonstrated the proposed microrobot under an ex vivo environment using a pig's stomach. Thus, this approach can be a potential alternative to targeted drug carriers, especially for stomach cancer applications.

Micromotor Manipulation Using Ultrasonic Active Traveling Waves.

The ability to manipulate therapeutic agents in fluids is of interest to improve the efficiency of targeted drug delivery. Ultrasonic manipulation has great potential in the field of therapeutic applications as it can trap and manipulate micro-scale objects. Recently, several methods of ultrasonic manipulation have been studied through standing wave, traveling wave, and acoustic streaming. Among them, the traveling wave based ultrasonic manipulation is showing more advantage for in vivo environments. In this paper, we present a novel ultrasonic transducer (UT) array with a hemispherical arrangement that generates active traveling waves with phase modulation to manipulate a micromotor in water. The feasibility of the method could be demonstrated by in vitro and ex vivo experiments conducted using a UT array with 16 transducers operating at 1 MHz. The phase of each transducer was controlled independently for generating a twin trap and manipulation of a micromotor in 3D space. This study shows that the ultrasonic manipulation device using active traveling waves is a versatile tool that can be used for precise manipulation of a micromotor inserted in a human body and targeted for drug delivery.

A Magnetically Guided Self-Rolled Microrobot for Targeted Drug Delivery, Real-Time X-Ray Imaging, and Microrobot Retrieval.

Targeted drug delivery using a microrobot is a promising technique capable of overcoming the limitations of conventional chemotherapy that relies on body circulation. However, most studies of microrobots used for drug delivery have only demonstrated simple mobility rather than precise targeting methods and prove the possibility of biodegradation of implanted microrobots after drug delivery. In this study, magnetically guided self-rolled microrobot that enables autonomous navigation-based targeted drug delivery, real-time X-ray imaging, and microrobot retrieval is proposed. The microrobot, composed of a self-rolled body that is printed using focused light and a surface with magnetic nanoparticles attached, demonstrates the loading of doxorubicin and an X-ray contrast agent for cancer therapy and X-ray imaging. The microrobot is precisely mobilized to the lesion site through automated targeting using magnetic field control of an electromagnetic actuation system under real-time X-ray imaging. The photothermal effect using near-infrared light reveals rapid drug release of the microrobot located at the lesion site. After drug delivery, the microrobot is recovered without potential toxicity by implantation or degradation using a magnetic-field-switchable coiled catheter. This microrobotic approach using automated control method of the therapeutic agents-loaded microrobot has potential use in precise localized drug delivery systems.