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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.)

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.)

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.)

Conclusions: Continuous topical drug delivery using an osmotic pump is an effective supplementary technique for hearing preservation after cochlear implantation, as demonstrated in a guinea pig model., Objective: To evaluate the effect of continuous topical steroid delivery via an osmotic pump in an animal cochlear implant model., Methods: Twenty-three guinea pigs were used for the study. The animals were divided into three groups: control group (n = 8), simple topical dexamethasone delivery group (sDEXA group, n = 7) and continuous topical dexamethasone delivery group (cDEXA, n = 8). The hearing thresholds of all animals were measured by pre-operative auditory brain stem responses (ABRs) at 2, 8, 16, 24, and 32 kHz. ABRs were re-evaluated after cochlear implantation, and the animals were sacrificed for hematoxylin and eosin staining., Results: The ABR threshold at 1 week post-operatively was significantly lower in the cDEXA group than in the control and sDEXA groups at most frequencies. Threshold shifts from baseline were statistically smaller in the cDEXA group than in the control and sDEXA groups at all frequencies. Histological analysis revealed decreased numbers of multi-nucleated giant cells and thinner histiocyte layers.

Biodegradable polymer droplet containing magnetosome demonstrates active propulsion by magnetic field. Magnetosome is extracted from magnetotactic bacteria, AMB-1. Mixture of magnetosome and sodium alginate composes into droplet using the microfluidic device applied Plateau-Rayleigh instability principle. The magnetosome-contained droplet selects its route at the bifurcate microchannels by magnetic field. This shows tissue targeting potential of the proposed drug delivery system.

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.)

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