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Peripheral vascular interventions (PVIs) offer several benefits to patients with lower extremity arterial diseases, including reduced pain, simpler anesthesia, and shorter recovery time, compared to open surgery. However, to monitor the endovascular tools inside the body, PVIs are conducted under X-ray fluoroscopy, which poses serious long-term health risks to physicians and patients. Shortwave infrared (SWIR) imaging of quantum dots (QDs) has shown great potential in bioimaging due to the non-ionizing penetration of SWIR light through tissues. In this paper, a QD-based magnetic guidewire and its system is introduced that allows X-ray-free detection under SWIR imaging and precise steering via magnetic manipulation. The QD magnetic guidewire contains a flexible silicone tube encapsulating a QD polydimethylsiloxane (PDMS) composite, where HgCdSe/HgS/CdS/CdZnS/ZnS/SiO 2 core/multi-shell QDs are dispersed in the PDMS matrix for SWIR imaging upon near-infrared excitation, as well as a permanent magnet for magnetic steering. The SWIR penetration of the QD magnetic guidewire is investigated within an artificial tissue model (1% Intralipid) and explore the potential for non-fluoroscopic PVIs within a vascular phantom model. The QD magnetic guidewire is biocompatible in its entirety, with excellent resistance to photobleaching and chemical alteration, which is a promising sign for its future clinical implementation., (© 2024 Wiley‐VCH GmbH.)

A spiral-artificial basilar membrane (S-ABM) sensor is reported that mimics the basilar membrane (BM) of the human cochlea and can detect sound by separating it into 24 sensing channels based on the frequency band. For this, an analytical function is proposed to design the width of the BM so that the frequency bands are linearly located along the length of the BM. To fabricate the S-ABM sensor, a spiral-shaped polyimide film is used as a vibrating membrane, with maximum displacement at locations corresponding to specific frequency bands of sound, and attach piezoelectric sensor modules made of poly(vinylidene fluoride-trifluoroethylene) film on top of the polyimide film to measure the vibration amplitude at each channel location. As the result, the S-ABM sensor implements a characteristic frequency band of 96-12,821 Hz and 24-independent critical bands. Using real-time signals from discriminate channels, it is demonstrated that the sensor can rapidly identify the operational noises from equipment processes as well as vehicle sounds from environmental noises on the road. The sensor can be used in a variety of applications, including speech recognition, dangerous situation recognition, hearing aids, and cochlear implants, and more., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Cd x Hg 1- x Se/HgS/Cd y Zn 1- y S core/multi-shell quantum dots (QDs) exhibiting bright tissue-penetrating shortwave infrared (SWIR; 1000-1700 nm) photoluminescence (PL) are engineered. The new structure consists of a quasi-type-II Cd x Hg 1- x Se/HgS core/inner shell domain creating luminescent bandgap tunable across SWIR window and a wide-bandgap Cd y Zn 1- y S outer shell boosting the PL quantum yield (QY). This compositional sequence also facilitates uniform and coherent shell growth by minimizing interfacial lattice mismatches, resulting in high QYs in both organic (40-80%) and aqueous (20-70%) solvents with maximum QYs of 87 and 73%, respectively, which are comparable to those of brightest visible-to-near infrared QDs. Moreover, they maintain bright PL in a photocurable resin (QY 40%, peak wavelength ≈ 1300 nm), enabling the fabrication of SWIR-luminescent composites of diverse morphology and concentration. These composites are used to localize controlled amounts of SWIR QDs inside artificial (Intralipid) and porcine tissues and quantitatively evaluate the applicability as luminescent probes for deep-tissue imaging., (© 2023 Wiley-VCH GmbH.)

Functional restoration by the re-establishment of cellular or neural connections remains a major challenge in targeted cell therapy and regenerative medicine. Recent advances in magnetically powered microrobots have shown potential for use in controlled and targeted cell therapy. In this study, a magnetic neurospheroid (Mag-Neurobot) that can form both structural and functional connections with an organotypic hippocampal slice (OHS) is assessed using an ex vivo model as a bridge toward in vivo application. The Mag-Neurobot consists of hippocampal neurons and superparamagnetic nanoparticles (SPIONs); it is precisely and skillfully manipulated by an external magnetic field. Furthermore, the results of patch-clamp recordings of hippocampal neurons indicate that neither the neuronal excitabilities nor the synaptic functions of SPION-loaded cells are significantly affected. Analysis of neural activity propagation using high-density multi-electrode arrays shows that the delivered Mag-Neurobot is functionally connected with the OHS. The applications of this study include functional verification for targeted cell delivery through the characterization of novel synaptic connections and the functionalities of transported and transplanted cells. The success of the Mag-Neurobot opens up new avenues of research and application; it offers a test platform for functional neural connections and neural regenerative processes through cell transplantation., (© 2023 Wiley-VCH GmbH.)

Robotic magnetic manipulation systems offer a wide range of potential benefits in medical fields, such as precise and selective manipulation of magnetically responsive instruments in difficult-to-reach vessels and tissues. However, more preclinical/clinical studies are necessary before robotic magnetic interventional systems can be widely adopted. In this study, a clinically translatable, electromagnetically controllable microrobotic interventional system (ECMIS) that assists a physician in remotely manipulating and controlling microdiameter guidewires in real time, is reported. The ECMIS comprises a microrobotic guidewire capable of active magnetic steering under low-strength magnetic fields, a human-scale electromagnetic actuation (EMA) system, a biplane X-ray imaging system, and a remote guidewire/catheter advancer unit. The proposed ECMIS demonstrates targeted real-time cardiovascular interventions in vascular phantoms through precise and rapid control of the microrobotic guidewire under EMA. Further, the potential clinical effectiveness of the ECMIS for real-time cardiovascular interventions is investigated through preclinical studies in coronary, iliac, and renal arteries of swine models in vivo, where the magnetic steering of the microrobotic guidewire and control of other ECMIS modules are teleoperated by operators in a separate control booth with X-ray shielding. The proposed ECMIS can help medical physicians optimally manipulate interventional devices such as guidewires under minimal radiation exposure., (© 2022 Wiley-VCH GmbH.)

A great deal of research has focused on small-scale robots for biomedical applications and minimally invasive delivery of therapeutics (e.g., cells, drugs, and genes) to a target area. Conventional fabrication methods, such as two-photon polymerization, can be used to build sophisticated micro- and nanorobots, but the long fabrication cycle for a single microrobot has limited its practical use. This study proposes a biodegradable spherical gelatin methacrylate (GelMA) microrobot for mass production in a microfluidic channel. The proposed microrobot is fabricated in a flow-focusing droplet generator by shearing a mixture of GelMA, photoinitiator, and superparamagnetic iron oxide nanoparticles (SPIONs) with a mixture of oil and surfactant. Human nasal turbinate stem cells (hNTSCs) are loaded on the GelMA microrobot, and the hNTSC-loaded microrobot shows precise rolling motion in response to an external rotating magnetic field. The microrobot is enzymatically degraded by collagenase, and released hNTSCs are proliferated and differentiated into neuronal cells. In addition, the feasibility of the GelMA microrobot as a cell therapeutic delivery system is investigated by measuring electrophysiological activity on a multielectrode array. Such a versatile and fully biodegradable microrobot has the potential for targeted stem cell delivery, proliferation, and differentiation for stem cell-based therapy., (© 2022 Wiley-VCH GmbH.)

Targeted stem cell delivery with microrobots has emerged as a potential alternative therapeutic strategy in regenerative medicine, and intranasal administration is an effective approach for minimally invasive delivery of therapeutic agents into the brain. In this study, a magnetically powered stem cell-based microrobot ("Cellbot") is used for minimally invasive targeted stem cell delivery to the brain through the intranasal passage. The Cellbot is developed by internalizing superparamagnetic iron oxide nanoparticles (SPIONs) into human nasal turbinate stem cells. The SPIONs have no influence on hNTSC characteristics, including morphology, cell viability, and neuronal differentiation. The Cellbots are capable of proliferation and differentiation into neurons, neural precursor cells, and neurogliocytes. The Cellbots in the microfluidic channel can be reliably manipulated by an external magnetic field for orientation and position control. Using an ex vivo model based on brain organoids, it is determined that the Cellbots can be transplanted into brain tissue. Using a murine model, it is demonstrated that the Cellbots can be intranasally administered and magnetically guided to the target tissue in vivo. This approach has the potential to effectively treat central nervous system disorders in a minimally invasive manner., (© 2021 Wiley-VCH GmbH.)

Therapeutic agents, such as drugs and cells, play an essential role in virtually every treatment of injury, illness, or disease. However, the conventional practices of drug delivery often result in undesirable side effects caused by drug overdose and off-target delivery. In the case of cell delivery, the survival rate of the transplanted cells is extremely low and difficulties with the administration route of cells remain a problem. Recently, magnetically actuated microrobots have started offering unique opportunities in targeted therapeutic delivery due to their tiny size and ability to access hard-to-reach lesions in a minimally invasive manner; considerable advances in this regard have been made over the past decade. Here, recent progress in magnetically actuated microrobots, developed for targeted drug/cell delivery, is presented, with a focus on their design features and mechanisms for controlled therapeutic release. Additionally, the practical challenges faced by the microrobots, and future research directions toward the swift bench-to-bedside translation of the microrobots are addressed., (© 2020 Wiley-VCH GmbH.)

Microrobots for targeted drug delivery are of great interest due to their minimal invasiveness and wireless controllability. Here, a magnetically driven porous degradable microrobot (PDM) is reported that consists of a 3D printed helical soft polymeric chassis made of a poly(ethylene glycol) diacrylate and pentaerythritol triacrylate matrix containing magnetite nanoparticles and the anticancer drug 5-fluorouracil (5-FU). The encapsulated Fe 3 O 4 nanoparticles render the PDM a precise wireless magnetic actuation by means of rotating magnetic fields (RMFs). The increased surface area of the porous PDM facilitates the acoustically induced drug release due to a higher response to the acoustic energy. The drug release profile from the PDM can be selected on command from three different modes, referred to herein as natural, burst, and constant, by differentiating the ultrasound exposure condition. Finally, in vitro test results reveal different therapeutic results for each release mode. The observed great reduction of cancer cell viability in the burst- and constant-release modes confirms that ultrasound with the proposed PDM can enhance the therapeutic effect by increasing drug concentration and sonoporation., (© 2020 Wiley-VCH GmbH.)

A needle-type microrobot (MR) for targeted drug delivery is developed to stably deliver drugs to a target microtissue (MT) for a given period time without the need for an external force after affixing. The MRs are fabricatedby 3D laser lithography and nickel (Ni)/titanium oxide (TiO 2 ) layers are coated by physical vapor deposition. The translational velocity of the MR is 714 µm s -1 at 20 mT and affixed to the target MT under the control of a rotating magnetic field. The manipulability of the MR is shown by using both manual and automatic controls. Finally, drug release from the paclitaxel-loaded MR is characterized to determine the efficiency of targeted drug delivery. This study demonstrates the utility of the proposed needle-type MR for targeted drug delivery to MT with various flow rates in vitro physiological fluidic environments., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A silicon carbonitride (SICN) ceramic microrobot, biocompatible and magnetically activable, is developed for the delivery of viable cells to defective tissue by sequential steps of microstructuring, magnetization, and cell loading. The ceramic carrier of porous cylindrical framework is fabricated by 3D laser lithography using a photocurable preceramic polymer, chemically modified polyvinylsilazane, and subsequent pyrolysis at 600 °C under an inert atmosphere. Magnetic nanoparticles (MNP) are integrated into the surface-modified ceramic carrier by thiol-ene click reaction. Finally, the microrobot is loaded with fibroblast cells, which can be guided by a rotating external magnetic field. The proposed ceramic microrobot is mechanically durable, adequately controllable with external magnetic field, and quite compatible with mammalian cells., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In cochlear implants, the electrode insertion trauma during surgery can cause damage residual hearing. Preserving the residual hearing is an important challenge and the localized administration of drugs, such as steroids, is one of the most promising ways, but remains a challenge. Here, a microscaffold cochlear electrode array (MiSCEA) consisting of a microfabricated flexible electrode array and a 3D microscaffold for steroid reservoir is reported. The MiSCEA without loaded drug is tested by measuring the electrically evoked auditory brainstem response of the cochlea in guinea pigs (n = 4). The scaffold is then coated with steroid (dexamethasone) encapsulated in polylactic-co-glycolic acid and the continuous release of the steroid into artificial perilymph during six weeks is monitored. The steroid-containing scaffolds are then implanted into guinea pigs (n = 4) and threshold shifts are analyzed for four weeks by measuring the acoustically evoked auditory brainstem response. The threshold shifts tend to be lower in the group implanted with the steroid-containing MiSCEAs. The feasibility of 3D MiSCEA opens up the development of potential next-generation cochlear electrode with improved steroid release dynamics into cochlea., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Microrobots facilitate targeted therapy due to their small size, minimal invasiveness, and precise wireless control. A degradable hyperthermia microrobot (DHM) with a 3D helical structure is developed, enabling actively controlled drug delivery, release, and hyperthermia therapy. The microrobot is made of poly(ethylene glycol) diacrylate (PEGDA) and pentaerythritol triacrylate (PETA) and contains magnetic Fe 3 O 4 nanoparticles (MNPs) and 5-fluorouracil (5-FU). Its locomotion is remotely and precisely controlled by a rotating magnetic field (RMF) generated by an electromagnetic actuation system. Drug-free DHMs reduce the viability of cancer cells by elevating the temperature under an alternating magnetic field (AMF), a hyperthermic effect. 5-FU is released from the proposed DHMs in normal-, high-burst-, and constant-release modes, controlled by the AMF. Finally, actively controlled drug release from the DHMs in normal- and high-burst-release mode results in a reduction in cell viability. The reduction in cell viability is of greater magnitude in high-burst- than in normal-release mode. In summary, biodegradable DHMs have potential for actively controlled drug release and hyperthermia therapy., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Biocompatibility and high responsiveness to magnetic fields are fundamental requisites to translate magnetic small-scale robots into clinical applications. The magnetic element iron exhibits the highest saturation magnetization and magnetic susceptibility while exhibiting excellent biocompatibility characteristics. Here, a process to reliably fabricate iron microrobots by means of template-assisted electrodeposition in 3D-printed micromolds is presented. The 3D molds are fabricated using a modified two-photon absorption configuration, which overcomes previous limitations such as the use of transparent substrates, low writing speeds, and limited depth of field. By optimizing the geometrical parameters of the 3D molds, metallic structures with complex features can be fabricated. Fe microrollers and microswimmers are realized that demonstrate motion at ≈20 body lengths per second, perform 3D motion in viscous environments, and overcome higher flow velocities than those of "conventional 3D printed helical microswimmers." The cytotoxicity of these microrobots is assessed by culturing them with human colorectal cancer (HCT116) cells for four days, demonstrating their good biocompatibility characteristics. Finally, preliminary results regarding the degradation of iron structures in simulated gastric acid liquid are provided., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A capsule-type microrobot exhibits "pick-and-drop" (P&D) motion to hold a particle within a confined volume and transports it via a corkscrewing motion. The P&D motion is possible because the capsule-type microrobot has two parts: a plunger and a cap. The fabricated microrobots are wirelessly controlled by a magnetic manipulator. Drugs or cells can be encapsulated in the container of the capsule-type microrobot by the P&D motion or attached to the surface of the cap, which can be used as a supporting structure. Therefore, the capsule-type microrobot can deliver suspended or adherent cells. The drug or cells are minimally exposed or not completely exposed to the surrounding fluid and do not experience shear force when encapsulated in the container. As a proof-of-concept, secure transportation of microparticles in the confined volume of the capsule via P&D motion is demonstrated. In addition, the cap is used as a scaffold for neuronal cell culture on a rat brain slice to demonstrate its biocompatibility and feasibility for targeted cell delivery. The proposed capsule-type microrobot is suitable for diverse applications, as it protects the encapsulated materials., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Patients with sensorineural hearing loss can recover their hearing using a cochlear implant (CI). However, there is a need to develop next-generation CIs to overcome the limitations of conventional CIs caused by extracorporeal devices. Recently, artificial basilar membranes (ABMs) are actively studied for next-generation CIs. The ABM is an acoustic transducer that mimics the mechanical frequency selectivity of the BM and acoustic-to-electrical energy conversion of hair cells. This paper presents recent progress in biomimetic ABMs. First, the characteristics of frequency selectivity of the ABMs by the trapezoidal membrane and beam array are addressed. Second, to reflect the latest research of energy conversion technologies, ABMs using various piezoelectric materials and triboelectric-based ABMs are discussed. Third, in vivo evaluations of the ABMs in animal models are discussed according to the target position for implantation. Finally, future perspectives of ABM studies for the development of practical hearing devices are discussed., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A triboelectric-based artificial basilar membrane (TEABM) can mimic cochlear tonotopy by triboelectrification between Kapton film and aluminum foil. The two films are stacked and clamped to form a beam structure. The TEABM tonotopy is tested using an animal model to verify the feasibility of a self-powered acoustic sensor for a prototype cochlear implant., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Magnetically manipulated microrobots are demonstrated for targeted cell transportation. Full three-dimensional (3D) porous structures are fabricated with an SU-8 photoresist using a 3D laser lithography system. Nickel and titanium are deposited as a magnetic material and biocompatible material, respectively. The fabricated microrobots are controlled in the fluid by external magnetic fields. Human embryonic kidney 239 (HEK 239) cells are cultivated in the microrobot to show the possibility for targeted cell transportation., (© 2013 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)