Multifunctional Nanorobot System for Active Therapeutic Delivery and Synergistic Chemo-photothermal Therapy.

Nanorobots are safe and exhibit powerful functionalities, including delivery, therapy, and diagnosis. Therefore, they are in high demand for the development of new cancer therapies. Although many studies have contributed to the progressive development of the nanorobot system for anticancer drug delivery, these systems still face some critical limitations, such as potentially toxic materials in the nanorobots, unreasonable sizes for passive targeting, and the lack of several essential functions of the nanorobot for anticancer drug delivery including sensing, active targeting, controlling drug release, and sufficient drug loading capacity. Here, we developed a multifunctional nanorobot system capable of precise magnetic control, sufficient drug loading for chemotherapy, light-triggered controlled drug release, light absorption for photothermal therapy, enhanced magnetic resonance imaging, and tumor sensing. The developed nanorobot system exhibits an in vitro synergetic antitumor effect of photothermal therapy and chemotherapy and outstanding tumor-targeting efficiency in both in vitro and in vivo environments. The results of this study encourage further explorations of an efficient active drug delivery system for cancer treatment and the development of nanorobot systems for other biomedical applications.

Preliminary study on alginate/NIPAM hydrogel-based soft microrobot for controlled drug delivery using electromagnetic actuation and near-infrared stimulus.

Currently, microrobots are receiving attention because of their small size and motility, which can be applied to minimal invasive therapy. Additionally, various microrobots using hydrogel with the characteristics of biocompatibility and biodegradability are also being developed. Among them, microrobots that swell and deswell in response to temperature changes caused by external near infrared (NIR) stimuli, focused ultrasound, and an alternating magnetic field, have been receiving a great amount of interest as drug carriers for therapeutic cell delivery. In this study, we propose a spring type medical microrobot that can be manipulated by an electromagnetic actuation (EMA) system and respond to an external stimulus (NIR). Additionally, we verified its feasibility with regard to targeting and drug delivery. There exist various methods of fabricating a spring type microrobot. In this study, we adopted a simple method that entails using a perfluoroalkoxy (PFA) microtube and a syringe pump. Moreover, we also used a hydrogel mixture composed of natural alginate, N-Isopropylacrylamide (NIPAM) for temperature responsiveness, and magnetic nanoparticles (MNPs) for electromagnetic control. Then, we fabricated a spring type alginate/NIPAM hydrogel-based soft microrobot. Additionally, we encapsulated doxorubicin (DOX) for tumor therapy in the microrobot. To verify the feasibility of the proposed spring type hydrogel-based soft microrobot's targeting and drug delivery, we developed an EMA and NIR integrated system. Finally, we observed the swelling and deswelling of the soft microrobot under NIR stimulation and verified the EMA controlled targeting. Moreover, we implemented a control function to release the encapsulated anticancer drug (DOX) through the swelling and deswelling of the soft microrobot by NIR, and evaluated the feasibility of cancer cell therapy by controlling the release of the drug from the soft microrobot.

Folate-receptor-targeted NIR-sensitive polydopamine nanoparticles for chemo-photothermal cancer therapy.

We propose the use of folate-receptor-targeted, near-infrared-sensitive polydopamine nanoparticles (NPs) for chemo-photothermal cancer therapy as an enhanced type of drug-delivery system which can be synthesized by in situ polymerization and conjugation with folic acid. The NPs consist of a Fe3O4/Au core, coated polydopamine, conjugated folic acid, and loaded anti-cancer drug (doxorubicin). The proposed multifunctional NPs show many advantages for therapeutic applications such as good biocompatibility and easy bioconjugation. The polydopamine coating of the NPs show a higher photothermal effect and thus more effective cancer killing compared to Fe3O4/Au nanoparticles at the same intensity as near-infrared laser irradiation. In addition, the conjugation of folic acid was shown to enhance cancer cellular uptake efficiency via the folate receptor and thus improve chemotherapeutic efficiency. Through in vitro cancer cell treatment testing, the proposed multifunctional NPs showed advanced photothermal and chemotherapeutic performance. Based on these enhanced anti-cancer properties, we expect that the proposed multifunctional NPs can be used as a drug-delivery system in cancer therapy.

Experimental and simulation studies on focused ultrasound triggered drug delivery.

To improve drug delivery efficiency in cancer therapy, many researchers have recently concentrated on drug delivery systems that use anticancer drug loaded micro- or nanoparticles. In addition, induction methods, such as ultrasound, magnetic field, and infrared light, have been considered as active induction methods for drug delivery. Among these, focused ultrasound has been regarded as a promising candidate for the active induction method of drug delivery system because it can penetrate a deep site in soft tissue, and its energy can be focused on the targeted lesion. In this research, we employed focused ultrasound as an active induction method. For an anticancer drug loaded microparticles, we fabricated poly-lactic-co-glycolic acid docetaxel (PLGA-DTX) nanoparticle encapsulated alginate microbeads using the single-emulsion technique and the aeration method. To select the appropriate operating parameter for the focused ultrasound, we measured the pressure and temperature induced by the focused ultrasound at the focal area using a needle-type hydrophone and a digital thermal detector, respectively. Additionally, we conducted a simulation of focused ultrasound using COMSOL Multiphysics 4.3a. The experimental measurement results were compared with the simulation results. In addition, the drug release rates of the PLGA-DTX-encapsulated alginate microbeads induced by the focused ultrasound were tested. Through these experiments, we determined that the appropriate focused ultrasound parameter was peak pressure of 1 MPa, 10 cycle/burst, and burst period of 20 µSec. Finally, we performed the cell cytotoxicity and drug uptake test with focused ultrasound induction and found that the antitumor effect and drug uptake efficiency were significantly enhanced by the focused ultrasound induction. Thus, we confirmed that focused ultrasound can be an effective induction method for an anticancer drug delivery system.

A soft biomolecule actuator based on a highly functionalized bacterial cellulose nano-fiber network with carboxylic acid groups.

Upcoming human-related applications such as soft wearable electronics, flexible haptic systems, and active bio-medical devices will require bio-friendly actuating materials. Here, we report a soft biomolecule actuator based on carboxylated bacterial cellulose (CBC), ionic liquid (IL), and poly (3,4-ethylenedioxythiophene)-poly(styrenesulfonate) ( PEDOT: PSS) electrodes. Soft and biocompatible polymer-IL composites were prepared via doping of CBC with ILs. The highly conductive PEDOT: PSS layers were deposited on both sides of the CBC-IL membranes by a dip-coating technique to yield a sandwiched actuator system. Ionic conductivity and ionic exchange capacity of the CBC membrane can be increased up to 22.8 times and 1.5 times compared with pristine bacterial cellulose (BC), respectively, resulting in 8 times large bending deformation than the pure BC actuators with metallic electrodes in an open air environment. The developed CBC-IL actuators show significant progress in the development of biocompatible and soft actuating materials with quick response, low operating voltage and comparatively large bending deformation.

Effect of chitosan coating on a bacteria-based alginate microrobot.

To develop an efficient bacteria-based microrobot, first, therapeutic bacteria should be encapsulated into microbeads using biodegradable and biocompatible materials; second, the releasing rate of the encapsulated bacteria for theragnostic function should be regulated; and finally, flagellated bacteria should be attached on the microbeads to ensure the motility of the microrobot. For the therapeutic bacteria encapsulation, an alginate can be a promising candidate as a biodegradable and biocompatible material. Owing to the non-regulated releasing rate of the encapsulated bacteria in alginate microbeads and the weak attachment of flagellated bacteria on the surface of alginate microbeads, however, the alginate microbeads cannot be used as effective cargo for a bacteria-based microrobot. In this paper, to enhance the stability of the bacteria encapsulation and the adhesion of flagellated bacteria in alginate microbeads, we performed a surface modification of alginate microbeads using chitosan coating. The bacteria-encapsulated alginate microbeads with 1% chitosan coating maintained their structural integrity up to 72 h, whereas the control alginate microbead group without chitosan coating showed severe degradations after 24 h. The chitosan coating in alginate microbeads shows the enhanced attachment of flagellated bacteria on the surface of alginate microbeads. The bacteria-actuated microrobot with the enhanced flagellated bacteria attachment could show approximately 4.2 times higher average velocities than the control bacteria-actuated microrobot without chitosan coating. Consequently, the surface modification using chitosan coating enhanced the structural stability and the motility of the bacteria-based alginate microrobots.

A hybrid actuated microrobot using an electromagnetic field and flagellated bacteria for tumor-targeting therapy.

In this paper, we propose a new concept for a hybrid actuated microrobot for tumor-targeting therapy. For drug delivery in tumor therapy, various electromagnetic actuated microrobot systems have been studied. In addition, bacteria-based microrobot (so-called bacteriobot), which use tumor targeting and the therapeutic function of the bacteria, has also been proposed for solid tumor therapy. Compared with bacteriobot, electromagnetic actuated microrobot has larger driving force and locomotive controllability due to their position recognition and magnetic field control. However, because electromagnetic actuated microrobot does not have self-tumor targeting, they need to be controlled by an external magnetic field. In contrast, the bacteriobot uses tumor targeting and the bacteria's own motility, and can exhibit self-targeting performance at solid tumors. However, because the propulsion forces of the bacteria are too small, it is very difficult for bacteriobot to track a tumor in a vessel with a large bloodstream. Therefore, we propose a hybrid actuated microrobot combined with electromagnetic actuation in large blood vessels with a macro range and bacterial actuation in small vessels with a micro range. In addition, the proposed microrobot consists of biodegradable and biocompatible microbeads in which the drugs and magnetic particles can be encapsulated; the bacteria can be attached to the surface of the microbeads and propel the microrobot. We carried out macro-manipulation of the hybrid actuated microrobot along a desired path through electromagnetic field control and the micro-manipulation of the hybrid actuated microrobot toward a chemical attractant through the chemotaxis of the bacteria. For the validation of the hybrid actuation of the microrobot, we fabricated a hydrogel microfluidic channel that can generate a chemical gradient. Finally, we evaluated the motility performance of the hybrid actuated microrobot in the hydrogel microfluidic channel. We expect that the hybrid actuated microrobot will be utilized for tumor targeting and therapy in future.

Motility analysis of bacteria-based microrobot (bacteriobot) using chemical gradient microchamber.

A bacteria-based microrobot (bacteriobot) was proposed and investigated as a new type of active drug delivery system because of its useful advantages, such as active tumor targeting, bacteria-mediated tumor diagnosis, and therapy. In this study, we fabricated a bacteriobot with enhanced motility by selective attachment of flagellar bacteria (Salmonella typhimurium). Through selective bovine serum albumin (BSA) pattering on hydrophobic polystyrene (PS) microbeads, many S. typhimurium could be selectively attached only on the unpatterned surface of PS microbead. For the evaluation of the chemotactic motility of the bacteriobot, we developed a microfluidic chamber which can generate a stable concentration gradient of bacterial chemotactic chemicals. Prior to the evaluation of the bacteriobot, we first evaluated the directional chemotactic motility of S. typhimurium using the proposed microfluidic chamber, which contained a bacterial chemo-attractant (L-aspartic acid) and a chemo-repellent (NiSO4 ), respectively. Compared to density of the control group in the microfluidic chamber without any chemical gradient, S. typhimurium increased by about 16% in the L-aspartic acid gradient region and decreased by about 22% in the NiSO4 gradient region. Second, we evaluated the bacteriobot's directional motility by using this microfluidic chamber. The chemotactic directional motility of the bacteriobot increased by 14% and decreased by 13% in the concentration gradients of L-aspartic acid and NiSO4 , respectively. These results confirm that the bacteriobot with selectively patterned S. typhimurium shows chemotaxis motility very similar to that of S. typhimurium. Moreover, the directional motilities of the bacteria and bacteriobot could be demonstrated quantitatively through the proposed microfluidic chamber.

Monocyte-based microrobot with chemotactic motility for tumor theragnosis.

Biocompatibility, sensing, and self-actuation are very important features for a therapeutic biomedical microrobot. As a new concept for tumor theragnosis, this paper proposes a monocyte-based microrobots, which are combining the phagocytosis and engulfment activities containing human acute monocytic leukemia cell line (THP-1) with various sized polystyrene microbeads are engulfed instead of a therapeutic drug. For the validation of the blood vessel barrier-penetrating activity of the monocyte-based microrobot, we fabricate a new cell migration assay with monolayer-cultured endothelial cell (HUVEC), similar with the blood vessels. We perform the penetrating chemotactic motility of the monocyte-based microrobot using various types of the chemo-attractants, such as monocyte chemotactic protein (MCP)-1, human breast cancer cell lines (MCF7)-cell lysates, and -contained alginate spheroids. The monocyte-based microrobot show chemotactic transmigrating motilities similar with what an actual monocyte does. This new paradigm of a monocyte-based microrobot having various useful properties such as biocompatibility, sensing, and self-actuation can become the basis of a biomedical microrobot using monocytes for diagnosis and therapy of various diseases.

Modulating nanostructures with polyvinylpyrrolidone: Design and development of a porous, biocompatible, and pH-Stable core-shell magnetic microrobot for demonstrating drug absorption from wastewater.

Increased antineoplastic drug concentrations in wastewater stem from ineffective treatment plants and increased usage. Although microrobots are promising for pollutant removal, they face hurdles in developing a superstructure with superior adsorption capabilities, biocompatibility, porosity, and pH stability. This study focused on adjusting the PVP concentration from 0.05 to 0.375 mM during synthesis to create a favorable CMOC structure for drug absorption. Lower PVP concentrations (0.05 mM) yielded a three-dimensional nanoflower structure of CaMoO4 and CuS nanostructures, whereas five-fold concentrations (0.25 mM) produced a porous structure with a dense CuS core encased in a transparent CaMoO4 shell. The magnetically movable and pH-stable COF@CMOC microrobot, achieved by attaching CMOC to cobalt ferrite (CoF) NPs, captured doxorubicin efficiently, with up to 57 % efficiency at 200 ng/mL concentration for 30 min, facilitated by electrostatic interaction, hydrogen bonding, and pore filling of DOX. The results demonstrated that DOX removal through magnetic motion showed superior performance, with an estimated improvement of 57% compared to stirring conditions (17 %). A prototype PDMS microchannel system was developed to study drug absorption and microrobot recovery. The CaMoO4 shell of the microrobots exhibited remarkable robustness, ensuring long-lasting functionality in harsh wastewater environments and improving biocompatibility while safeguarding the CuS core from degradation. Therefore, microrobots are a promising eco-friendly solution for drug extraction. These microrobots show promise for the selective removal of doxorubicin from contaminated wastewater.

A self-assembled three-dimensional hierarchical nanoflower: an efficient enzyme-mimetic material for cancer cell detection that improves ROS generation for therapy.

Three-dimensional (3D) nanomaterials with high functional properties are emerging as the most promising artificial enzymes for overcoming the significant disadvantages of natural enzymes. Anticancer therapy using 3D-enzyme mimetic materials has emerged as an essential development for catalyzing cancer cell destruction. We report for the first time a novel 3D-based enzyme mimetic material, CaMoO4/MoS2/CuS nanoflower (CMC NF), that exhibits a large specific surface area, uniform flower-like structure, excellent biocompatibility, and high porosity, making it a suitable candidate for cancer detection and therapy. Additionally, CMC NFs were conjugated with folic acid (FA) to selectively target cancer cells, resulting in FA-CMC NFs explicitly binding to overexpressed folate receptor alpha (FRα) in MDA-MB-231 cells. Based on the peroxidase activity, the FA-CMC NFs are an effective nanoprobe for the selective detection of MDA-MB-231 cells over a wide detection range (50 to 5.5 × 104 cells per mL) with a low limit of detection (LOD) value of 10 cells per mL. In addition to their cancer detection capability, the FA-CMC NFs also effectively generated ˙OH radicals in a concentration-dependent manner to treat cancer cells. Under light conditions, the FA-CMC NFs with H2O2 solution showed efficient degradation of methylene blue (MB) dye, and the solution color appeared to fade within 15 min, indicating that they generated ˙OH radicals, which can efficiently kill cancer cells. Thus, the superior functionality of FA-CMC NFs offers cost-effective, facile, and reliable cancer cell detection, providing a new treatment option for cancer treatment and diagnosis.

Selective bacterial patterning using the submerged properties of microbeads on agarose gel.

We proposed a new bacteria patterning method on the restricted region of microbeads, using the submerged property of polystyrene microbeads on various concentrations of agarose gel. Moreover, we fabricated a bacterial microrobot using attenuated Salmonella typhimurium through the new patterning methods. We controlled the submerged degree of polystyrene microbeads through the regulation of the hardness of the agarose gel. The polystyrene microbeads on agarose gel were transferred onto a poly-dimethylsiloxane (PDMS) surface for easy manipulation of the microbeads. Then, we treated the polystyrene microbeads on the PDMS surface with antibacterial adherent factors, such as O2 plasma and bovine serum albumin (BSA). The Salmonella typhimurium was attached to the entire surface of the untreated polystyrene microbeads, whereas Salmonella typhimurium were only attached to the restricted surface region of the treated polystyrene microbeads through the proposed patterning method. The bacteria-attached microbeads gain motility by the propulsion of the attached bacteria, and the selective-bacteria-attached microbeads showed enhanced motility. Compared with whole-bacteria-attached polystyrene microbeads (1.74 ± 1.62 µm/s), the selective bacteria-attached polystyrene microbeads, using O2 plasma and BSA, showed 9.18 ± 1.88 µm/s and 14.65 ± 8.66 µm/s faster moving velocities, respectively. Through the results, we expected that the proposed patterning methodology of microbeads could contribute to the development of biomedical bacterial microrobots.

Magnetically Actuated Helical Microrobot with Magnetic Nanoparticle Retrieval and Sequential Dual-Drug Release Abilities.

Cancer is one of the diseases with high mortality worldwide. Various methods for cancer treatment are being developed, and among them, magnetically driven microrobots capable of minimally invasive surgery and accurate targeting are in the spotlight. However, existing medical magnetically manipulated microrobots contain magnetic nanoparticles (MNPs), which can cause toxicity to normal cells after the delivery of therapeutic drugs. In addition, there is a limitation in that cancer cells become resistant to the drug by mainly delivering only one drug, thereby reducing the treatment efficiency. In this paper, to overcome these limitations, we propose a microrobot that can separate/retrieve MNPs after precise targeting of the microrobot and can sequentially deliver dual drugs (gemcitabine (GEM) and doxorubicin (DOX)). First, after the proposed microrobot targeting, MNPs attached to the microrobot surface can be separated from the microrobot using focused ultrasound (FUS) and retrieved through an external magnetic field. Second, the active release of the first conjugated drug GEM to the surface of the microrobot is possible using near-infrared (NIR), and as the microrobot slowly decomposes over time, the release of the second encapsulated DOX is possible. Therefore, it is possible to increase the cancer cell treatment efficiency with sequential dual drugs in the microrobot. We performed basic experiments on the targeting of the proposed magnetically manipulated microrobot, separation/retrieval of MNPs, and the sequential dual-drug release and validated the performances of the microrobot through in vitro experiments using the EMA/FUS/NIR integrated system. As a result, the proposed microrobot is expected to be used as one of the methods to improve cancer cell treatment efficiency by improving the limitations of existing microrobots in cancer cell treatment.

Tumor-targeted molybdenum disulfide@barium titanate core-shell nanomedicine for dual photothermal and chemotherapy of triple-negative breast cancer cells.

Combinational therapy can improve the effectiveness of cancer treatment by overcoming individual therapy shortcomings, leading to accelerated cancer cell apoptosis. Combinational cancer therapy is attained by a single nanosystem with multiple physicochemical properties providing an efficient synergistic therapy against cancer cells. Herein, we report a folate receptor-targeting dual-therapeutic (photothermal and chemotherapy) core-shell nanoparticle (CSNP) exhibiting a molybdenum disulfide core with a barium titanate shell (MoS2@BT) to improve therapeutic efficacy against triple-negative breast cancer (TNBC) MDA-MB-231 cells. A simple hydrothermal approach was used to achieve the MoS2@BT CSNPs, and their diameter was calculated to be approximately 180 ± 25 nm. In addition to improving the photothermal efficiency and stability of the MoS2@BT CSNPs, their surface was functionalized with polydopamine (PDA) and subsequently modified with folic acid (FA) to achieve enhanced tumour-targeting CSNPs, named MoS2@BT-PDA-FA (MBPF). Then, gemcitabine (Gem) was loaded into the MBPF, and its loading and releasing efficacy were calculated to be 17.5 wt% and 64.5 ± 3%, respectively. Moreover, the photothermal conversion efficiency (PCE) of MBPF was estimated to be 35.3%, and it also showed better biocompatibility, which was determined by an MTT assay. The MBPF significantly increased the ambient temperature to 56.3 °C and triggered Gem release inside the TNBC cells when exposed to a near-infrared (NIR) laser (808 nm, 1.5 W cm-2, 5 min). Notably, the MoS2@BT-based nanosystem was used as a photothermal agent and a therapeutic drug-loading container for combating TNBC cells. Benefiting from the combined therapy, MBPF reduced TNBC cell viability to 81.3% due to its efficient synergistic effects. Thus, the proposed tumour-targeting MoS2@BT CSNP exhibits high drug loading, better biocompatibility, and improved anticancer efficacy toward TNBC cells due to its dual therapeutic approach in a single system, which opens up a new approach for dual cancer therapy.

A dual stimuli-responsive smart soft carrier using multi-material 4D printing.

This paper proposes a 4D printed smart soft carrier with a hemispherical hollow and openable lid. The soft carrier is composed of a lid with a slot (with a shape of 4 legs), a border, and a hemisphere. The soft carrier is fabricated by 4D printing using smart hydrogels. Specifically, the lid, border, and hemisphere are fabricated using a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel, a non-responsive polyethylene glycol (PEG) hydrogel with superparamagnetic iron oxide nanoparticles (SPIONs), and a PEG hydrogel, respectively. Since the SPIONs are included in the border, the slot in the center of the lid is opened and closed according to the temperature change caused by near-infrared (NIR) irradiation, and the proposed soft carrier is magnetically driven by an external magnetic field. The hemisphere enables the storage and transport of cargo. The proposed soft carrier can control the opening and closing of the slot and movement to a desired position in water. Several cargo delivery experiments were conducted using various shapes and numbers of cargo. In addition, the proposed soft carrier can successfully handle small living marine organisms. This soft carrier can be manufactured by 4D printing and operated by dual stimuli (NIR and magnetic field) and can safely deliver various types of cargo and delicate organisms without leakage or damage. The flexibility of 4D printing enables the size of the soft carrier to be tailored to the specific physical attributes of various objects, making it an adaptable and versatile delivery approach.

Development of bacteria-based microrobot using biocompatible poly(ethylene glycol).

For the development of bacteria-based biomedical microrobot, we propose the fabrication method of biocompatible poly(ethylene glycol) (PEG) microbeads using a cross-junction microfluidic channel. PEG droplets were polymerized by ultraviolet (UV) irradiation to form PEG microbeads of 8.18 ± 3.4 µm diameter in a microfluidic channel. Generally, the bacteria did not attach to the surface of the PEG microbeads because of their hydrophilicity. We modified the selective surface of the PEG microbeads using poly-L-lysine (PLL), promoting attenuated Salmonella typhimurium adhesion using the submerging property of PEG microbeads on agarose gel: the bacteria could thus be attached to the PLL-coated surface region of the PEG microbeads. The selectively PLL-coated PEG microbeads group showed enhanced motility compared with the PLL-uncoated and completely PLL-coated PEG microbeads groups. The selectively PLL-coated PEG microbeads group showed 12.33 and 7.40 times higher average velocities than the PLL-uncoated and completely PLL-coated PEG microbeads groups, respectively. This study verified the successful fabrication of bacteria-based microrobots using PEG microbeads, and the enhanced motility of the microrobots by selective bacteria patterning using agarose gel and PLL.

Enhanced sensing and electrical performance of hierarchical porous ionic polymer-metal nanocomposite via minimizing cracks in electrode.

High-performance foldable metal-coated ionic polymer-metal nanocomposites (IPMNCs) with crack minimized electrode are desired for wearable electronics, energy harvesting devices, tactile sensors, structural health monitors, humidity sensors, and supercapacitor devices. However, the IPMNC shows the cracked structure that seriously decreases the performance of IPMNCs for sensors and actuators applications. To overcome the issue of the cracked metal electrode, here we propose a metal-coated hierarchical porous structured IPMNC via minimizing the cracks in the Platinum (Pt) electrode using attachment of poly(2-acrylamide-2-methyl-1-propane-sulfonic acid) (PAMPS) in poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE))/polyvinylpyrrolidone (PVP) blend. The crack-minimized Pt electrode deposition on PAMPS attached P(VDF-TrFE)/PVP-based IPMNCs showed enhanced electrical and sensing signals compared to the Nafion, ionic liquid, and polystyrene sulphonic acid-based IPMNCs. The developed IPMNCs with an optimized composition depict stable sensing signals up to 10,000 cycles. The hierarchical porous structure and the crack-minimized metal electrode on the P(VDF-TrFE)/PVP/PAMPS IPMNC can be utilized in various attractive applications such as energy harvesting, wearable electronics, humidity sensor, pulse, braille recognition, catalyst supports, bio-interfacing, and sensors.

Study on Intention Recognition and Sensory Feedback: Control of Robotic Prosthetic Hand Through EMG Classification and Proprioceptive Feedback Using Rule-based Haptic Device.

In this study, for intention recognition, a convolutional neural network (CNN) classification model using the electromyography (EMG) signals acquired from the subject was developed. For sensory feedback, a rule-based wearable proprioceptive feedback haptic device, a new method for providing feedback on the grip information of a robotic prosthesis was proposed. Then, we constructed a closed-loop integrated system consisting of the CNN-based EMG classification model, the proposed haptic device, and a robotic prosthetic hand. Finally, an experiment was conducted in which the closed-loop integrated system was used to simultaneously evaluate the performance of the intention recognition and sensory feedback for a subject. The trained EMG classification model and the proposed haptic device showed the intention recognition and sensory feedback performance with 97% or higher accuracy in 10 grip states. Although some errors occurred in the intention recognition using the EMG classification model, in general, the grip intention of the subject was grasped relatively accurately, and the grip pattern was also accurately transmitted to the subject by the proposed haptic device. The integrated system which consists of the intention recognition using the CNN-based EMG classification model and the sensory feedback using the proposed haptic device is expected to be utilized for robotic prosthetic hand prosthesis control of limb loss participants.

Magnetically Actuated Drug Delivery Helical Microrobot with Magnetic Nanoparticle Retrieval Ability.

Therapeutic drug delivery microrobots capable of accurate targeting using an electromagnetic actuation (EMA) system are being developed. However, these drug delivery microrobots include a large number of magnetic nanoparticles (MNPs) for accurate EMA targeting, which causes side effects, such as problems with membrane integrity and normal cell apoptosis. Here, a biocompatible and hydrolyzable PEGDA-based drug delivery helical microrobot capable of MNP retrieval is proposed in which doxorubicin (DOX), an anticancer drug, is encapsulated and MNPs are conjugated by a disulfide bond. After being accurately delivered to the lesion of cancer cells through magnetic field manipulation, the fabricated microrobot provides rapid MNP separation and retrieval from the microrobot because of the use of dithiothreitol (DTT), a reducing agent, as an environment similar to the surrounding cancer cells and near-infrared (NIR) as an external stimulus. The characteristics of the fabricated microrobot are analyzed, and fundamental tests for active electromagnetic field manipulation, separation/retrieval of MNPs from the microrobot, and its hydrolysis are discussed. The therapeutic performance of the fabricated microrobot is verified through an in vitro test using tumor cells. Consequently, by use of an integrated system of microscope, eight-coil EMA, and NIR it is shown that the proposed microrobot can be moved to the target site by electromagnetic manipulation. The MNPs conjugated to the microrobot can be separated and retrieved, and the therapeutic effect on tumor cells by the encapsulated drug can be seen.

Magnetism-controlled assembly of composite stem cell spheroids for the biofabrication of contraction-modulatory 3D tissue.

Biofabrication of organ-like engineered 3D tissue through the assembly of magnetized 3D multi-cellular spheroids has been recently investigated in tissue engineering. However, the cytotoxicity of magnetic nanoparticles (MNPs) and contraction-induced structural deformation of the constructs have been major limitations. In this study, we developed a method to fabricate composite stem cell spheroids using MNP-coated fibers, alleviating MNP-mediated toxicity and controlling structural assembly under external magnetic stimuli. The MNP-coated synthetic fibers (MSFs) were prepared by coating various amounts of MNPs on the fibers via electrostatic interactions. The MSFs showed magnetic hysteresis and no cytotoxicity on 2D-cultured adipose-derived stem cells (ADSCs). The composite spheroids containing MSFs and ADSCs were rapidly formed in which the amount of impregnated MSFs modulated the spheroid size. The fusion ofin vitrocomposite spheroids was then monitored at the contacting interface; the fused spheroids with over 10µg of MSF showed minimal contraction after 7 d, retaining around 90% of total area ratio regardless of the number of cells, indicating that the presence of fibers within the composite spheroid supported its structural maintenance. The fusion of MSF spheroids was modulated by external magnetic stimulation, and the effect of magnetic force on the movement and fusion of the spheroids was investigated using COMSOL simulation. Finally, ring and lamellar structures were successfully assembled using remote-controlled MSF spheroids, showing limited deformation and high viability up to 50 d duringin vitroculture. In addition, the MSFs demonstrated no adverse effects on ADSC osteochondral differentiation. Altogether, we envision that our magnetic assembly system would be a promising method for the tissue engineering of structurally controlled organ-like constructs.