Publications by authors named "Sukho Park"

43 Publications

Exosome-based hybrid nanostructures for enhanced tumor targeting and hyperthermia therapy.

Colloids Surf B Biointerfaces 2021 Sep 8;205:111915. Epub 2021 Jun 8.

Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea. Electronic address:

Recently, natural exosomes have attracted attention as an ideal drug carrier to overcome the limitations of existing drug delivery systems which are toxicity induction and low cancer-targeting performance. In this study, we propose an exosome-based hybrid nanostructure (EHN) with improved targeting ability and therapeutic efficacy against colorectal cancer by using exosomes isolated from the tumor cell line as a drug carrier. The proposed EHN can have high biocompatibility by using exosomes, a biologically derived material, and show improved targeting performance by adding a tumor-targeting ligand (folic acid). In addition, the proposed EHN is capable of chemotherapy because doxorubicin, an anticancer drug, is encapsulated by the exosome with high efficiency, and it can induce hyperthermia therapy because of the magnetic nanoparticles (MNPs) attached to the surface of exosomes. Through in vitro and in vivo experiments using a xenograft tumor mouse model, it was confirmed that the proposed EHN could exhibit increased apoptosis and excellent tumor growth inhibition ability. Therefore, the proposed EHN is expected to overcome the limitations of existing drug delivery systems and be utilized as an effective drug delivery system in cancer treatment.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111915DOI Listing
September 2021

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

ACS Appl Mater Interfaces 2021 May 20;13(17):19633-19647. Epub 2021 Apr 20.

Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea.

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 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.
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http://dx.doi.org/10.1021/acsami.1c01742DOI Listing
May 2021

Active delivery of multi-layer drug-loaded microneedle patches using magnetically driven capsule.

Med Eng Phys 2020 11 30;85:87-96. Epub 2020 Sep 30.

Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea. Electronic address:

In this paper, we propose the active delivery of multi-layer drug-loaded microneedle (MN) patches using a capsule that can be driven by an external magnetic field. Firstly, the multi-layer drug-loaded MN patches consist of three delivered MN patches which are composed of a drug-loaded MN patch and polydimethylsiloxane layer. The drug-loaded MN patch is made of a 10% gelatin solution and a drug. The multi-layer MN patches are attached to a permanent magnet in a magnetically driven capsule. Under an external magnetic field generated by an electromagnetic actuation system, the capsule with the multi-layer MN patches can reach the target lesions, and each MN patch can be delivered to the target lesions for medical treatment. The active delivery of the multi-layer MN patches using the proposed magnetically driven capsule was confirmed via phantom experiments. Accordingly, the adhesion of the three separated faces of the multi-layer MN patches and the adhesion between the porcine small intestine and the MN patch were measured using a load cell. We demonstrate the feasibility of the active delivery of the multi-layer MN patches to the target lesions on a porcine small intestine. Consequently, we expect that the active delivery of the multi-layer drug-loaded MN patches using the magnetically driven capsule presented in this study can be a useful method for drug delivery to lesions at various locations in the gastrointestinal tract.
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http://dx.doi.org/10.1016/j.medengphy.2020.09.012DOI Listing
November 2020

Bilayer Hydrogel Sheet-Type Intraocular Microrobot for Drug Delivery and Magnetic Nanoparticles Retrieval.

Adv Healthc Mater 2020 07 19;9(13):e2000118. Epub 2020 May 19.

Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology, Daegu, 42988, Republic of Korea.

By virtue of minimum invasiveness and driving ability using a magnetic field, drug delivery with the aid of a microrobot has an inherent potential for targeted treatment for the eye. The use of microrobots, however, has the limitation of leaving magnetic nanoparticles (MNPs) in the eye that can cause side effects. In this study, a bilayer hydrogel microrobot capable of retrieving MNPs after drug delivery is proposed that overcomes the limitations of existing microrobots. The bilayer hydrogel microrobot is composed of an MNPs layer and a therapeutic layer. Upon applying an alternating magnetic field (AMF) at the target point, the therapeutic layer is dissolved to deliver drug particles, and then the MNPs layer can be retrieved using a magnetic field. The targeting and MNPs retrieval tests validate the drug delivery and MNPs retrieval ability of the microrobot. The ex vivo bovine vitreous and in vitro cell tests demonstrate the potential for the vitreous migration of the microrobot and the therapeutic effect against retinoblastoma Y79 cancer cells. This bilayer hydrogel sheet-type intraocular microrobot provides a new drug delivery paradigm that overcomes the limitations of microrobot by maintaining the advantages of conventional microrobots in delivering drugs to the eye and retrieving MNPs after drug delivery.
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http://dx.doi.org/10.1002/adhm.202000118DOI Listing
July 2020

Targeted removal of leukemia cells from the circulating system by whole-body magnetic hyperthermia in mice.

Nanoscale 2020 Jan 20;12(4):2773-2786. Epub 2020 Jan 20.

Companion Diagnostics and Medical Technology Research Group, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.

Until now, magnetic hyperthermia was used to remove solid tumors by targeting magnetic nanoparticles (MNPs) to tumor sites. In this study, leukemia cells in the bloodstream were directly removed by whole-body hyperthermia, using leukemia cell-specific MNPs. An epithelial cellular adhesion molecule (EpCAM) antibody was immobilized on the surface of MNPs (EpCAM-MNPs) to introduce the specificity of MNPs to leukemia cells. The viability of THP1 cells (human monocytic leukemia cells) was decreased to 40.8% of that in control samples by hyperthermia using EpCAM-MNPs. In AKR mice, an animal model of lymphoblastic leukemia, the number of leukemia cells was measured following the intravenous injection of EpCAM-MNPs and subsequent whole-body hyperthermia treatment. The result showed that the leukemia cell number was also decreased to 43.8% of that without the treatment of hyperthermia, determined by Leishman staining of leukemia cells. To support the results, simulation analysis of heat transfer from MNPs to leukemia cells was performed using COMSOL Multiphysics simulation software. The surface temperature of leukemia cells adhered to EpCAM-MNPs was predicted to be increased to 82 °C, whereas the temperature of free cells without adhered MNPs was predicted to be 38 °C. Taken together, leukemia cells were selectively removed by magnetic hyperthermia from the bloodstream, because EpCAM-modified magnetic particles were specifically attached to leukemia cell surfaces. This approach has the potential to remove metastatic cancer cells, and pathogenic bacteria and viruses floating in the bloodstream.
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http://dx.doi.org/10.1039/c9nr06730bDOI Listing
January 2020

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

Nano Lett 2019 12 11;19(12):8550-8564. Epub 2019 Nov 11.

Korea Institute of Medical Microrobotics , 43-26 Cheomdangwagi-ro , Buk-gu, Gwangju 61011 , Republic of Korea.

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 synergetic antitumor effect of photothermal therapy and chemotherapy and outstanding tumor-targeting efficiency in both and 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.
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http://dx.doi.org/10.1021/acs.nanolett.9b03051DOI Listing
December 2019

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

Biomed Microdevices 2018 11 16;20(4):103. Epub 2018 Nov 16.

Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.

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.
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http://dx.doi.org/10.1007/s10544-018-0344-yDOI Listing
November 2018

Real-time microrobot posture recognition via biplane X-ray imaging system for external electromagnetic actuation.

Int J Comput Assist Radiol Surg 2018 Nov 20;13(11):1843-1852. Epub 2018 Aug 20.

School of Mechanical Engineering, Chonnam National University, Gwangju, 61186, South Korea.

Purpose: As a promising intravascular therapeutic approach for autonomous catheterization, especially for thrombosis treatment, a microrobot or robotic catheter driven by an external electromagnetic actuation system has been recently investigated. However, the three-dimensional (3D) real-time position and orientation tracking of the microrobot remains a challenge for precise feedback control in clinical applications owing to the micro-size of the microrobot geometry in vessels, along with bifurcation and vulnerability. Therefore, in this paper, we propose a 3D posture recognition method for the unmanned microrobotic surgery driven by an external electromagnetic actuator system.

Methods: We propose a real-time position and spatial orientation tracking method for a millimeter-sized intravascular object or microrobot using a principal component analysis algorithm and an X-ray reconstruction. The suggested algorithm was implemented to an actual controllable wireless microrobot system composed of a bullet-shaped object, a biplane X-ray imaging device, and an electromagnetic actuation system. Numerical computations and experiments were conducted for the performance verification.

Results: The experimental results showed a good performance of the implemented system with tracking errors less than 0.4 mm in position and 2° in orientation. The proposed tracking technique accomplished a fast processing time, ~ 0.125 ms/frame, and high-precision recognition of the micro-sized object.

Conclusions: Since the suggested method does not require pre-information of the object geometry in the human body for its 3D shape and position recognition, it could be applied to various elliptical shapes of the microrobot system with computation time efficacy and recognition accuracy. Hence, the method can be used for therapeutic millimeter- or micron-sized manipulator recognition in vascular, as well as implanted objects in the human body.
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http://dx.doi.org/10.1007/s11548-018-1846-zDOI Listing
November 2018

Dual tumor-targeted multifunctional magnetic hyaluronic acid micelles for enhanced MR imaging and combined photothermal-chemotherapy.

Colloids Surf B Biointerfaces 2018 Apr 5;164:424-435. Epub 2018 Feb 5.

School of Mechanical Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Republic of Korea; Medical Microrobot Center (MRC) and Robot Research Initiative (RRI), Chonnam National University, 43-26, Cheomdangwagi-ro 208-beon-gil, Buk-gu, Gwangju 61011, Republic of Korea. Electronic address:

Multifunctional polymeric micelles were developed as a promising dual tumor-targeted drug delivery platform for magnetic resonance (MR) imaging and combined photothermal-chemotherapy. HA-C copolymers were synthesized via peptide formation process with subsequent co-encapsulation of therapeutic agent docetaxel (DTX) and superparamagnetic iron oxide nanoparticles (SPIONs) to form the multifunctional micelles. The micelles exhibited uniform nanosize and remarkable colloidal stability in aqueous solution. The sustained drug release behavior from HA micelles was observed over the test period. Moreover, the specific targeting capability based on CD44 recptor-mediated endocytosis and the enhanced targeting efficacy by in presence of external magnetic field were investigated. The clustered SPIONs within micelles exerted excellent contrast effect with high r relaxivity in MR phantom test. Furthermore, the multifunctional micelles could readily convert light to heat to hyperthermia temperature upon near infrared light irradition and induce photothermal ablation to breast cancer cells. The combined photothermal therapy with DTX-mediated chemotherapy of the developed multifunctional polymeric micells could generate a synergistic therapeutic effect. Based on these findings, the resulting multifunctional micelles may provide high potential for multimodality theragnosis of cancer.
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http://dx.doi.org/10.1016/j.colsurfb.2018.02.005DOI Listing
April 2018

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

Nanotechnology 2017 Oct;28(42):425101

School of Mechanical Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea.

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 FeO/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 FeO/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.
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http://dx.doi.org/10.1088/1361-6528/aa8477DOI Listing
October 2017

A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair.

Adv Healthc Mater 2017 Jul 8;6(13). Epub 2017 May 8.

School of Mechanical Systems Engineering, Chonnam National University, Gwangju, 500-757, South Korea.

This study proposes a magnetically actuated microscaffold with the capability of targeted mesenchymal stem cell (MSC) delivery for articular cartilage regeneration. The microscaffold, as a 3D porous microbead, is divided into body and surface portions according to its materials and fabrication methods. The microscaffold body, which consists of poly(lactic-co-glycolic acid) (PLGA), is formed through water-in-oil-in-water emulsion templating, and its surface is coated with amine functionalized magnetic nanoparticles (MNPs) via amino bond formation. The porous PLGA structure of the microscaffold can assist in cell adhesion and migration, and the MNPs on the microscaffold can make it possible to steer using an electromagnetic actuation system that provides external magnetic fields for the 3D locomotion of the microscaffold. As a fundamental test of the magnetic response of the microscaffold, it is characterized in terms of the magnetization curve, velocity, and 3D locomotion of a single microscaffold. In addition, its function with a cargo of MSCs for cartilage regeneration is demonstrated from the proliferation, viability, and chondrogenic differentiation of D1 mouse MSCs that are cultured on the microscaffold. For the feasibility tests for cartilage repair, 2D/3D targeting of multiple microscaffolds with the MSCs is performed to demonstrate targeted stem cell delivery using the microscaffolds and their swarm motion.
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http://dx.doi.org/10.1002/adhm.201601378DOI Listing
July 2017

Nanohybrid magnetic liposome functionalized with hyaluronic acid for enhanced cellular uptake and near-infrared-triggered drug release.

Colloids Surf B Biointerfaces 2017 Jun 8;154:104-114. Epub 2017 Mar 8.

School of Mechanical Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea; Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology, 333 Techno Jungang-daero, Hyeonpung-myeon, Dalseong-gun, Daegu, 42988, Republic of Korea. Electronic address:

The aim of this work is to prepare and evaluate a novel lipid-polymer hybrid liposomal nanoplatform (hyaluronic acid-magnetic nanoparticle-liposomes, HA-MNP-LPs) as a vehicle for targeted delivery and triggered release of an anticancer drug (docetaxel, DTX) in human breast cancer cells. We first synthesize an amphiphilic hyaluronic acid hexadecylamine polymer (HA-C) to enhance the targeting ability of the hybrid liposome. Next, HA-MNP-LPs are constructed to achieve an average size of 189.93±2.74nm in diameter. In addition, citric acid-coated magnetic nanoparticles (MNPs) are prepared and embedded in the aqueous cores while DTX is encapsulated in the hydrophobic bilayers of the liposomes. Experiments with coumarin 6 loaded hybrid liposomes (C6/HA-MNP-LPs) show that the hybrid liposomes have superior cellular uptake in comparison with the conventional non-targeting liposomes (C6/MNP-LPs), and the result is further confirmed by Prussian blue staining. Under near-infrared laser irradiation (NIR, 808nm), the HA-MNP-LPs aqueous solution can reach 46.7°C in 10min, and the hybrid liposomes released over 20% more drug than the non-irradiated liposomes. Using a combination of photothermal irradiation and chemotherapy, the DTX-loaded hybrid liposomes (DTX/HA-MNP-LPs) significantly enhance therapeutic efficacy, with the IC value of 0.69±0.10μg/mL, which is much lower than the values for DTX monotherapy. Consequently, the prepared hybrid nanoplatform may offer a promising drug delivery vehicle with selective targeting and enhanced drug release in treating CD44-overexpressing cancers.
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http://dx.doi.org/10.1016/j.colsurfb.2017.03.008DOI Listing
June 2017

Virtual wall-based haptic-guided teleoperated surgical robotic system for single-port brain tumor removal surgery.

Proc Inst Mech Eng H 2017 Jan 18;231(1):3-19. Epub 2016 Nov 18.

1 Department of Mechanical Engineering, Chonnam National University, Gwangju, Korea.

This article presents a haptic-guided teleoperation for a tumor removal surgical robotic system, so-called a SIROMAN system. The system was developed in our previous work to make it possible to access tumor tissue, even those that seat deeply inside the brain, and to remove the tissue with full maneuverability. For a safe and accurate operation to remove only tumor tissue completely while minimizing damage to the normal tissue, a virtual wall-based haptic guidance together with a medical image-guided control is proposed and developed. The virtual wall is extracted from preoperative medical images, and the robot is controlled to restrict its motion within the virtual wall using haptic feedback. Coordinate transformation between sub-systems, a collision detection algorithm, and a haptic-guided teleoperation using a virtual wall are described in the context of using SIROMAN. A series of experiments using a simplified virtual wall are performed to evaluate the performance of virtual wall-based haptic-guided teleoperation. With haptic guidance, the accuracy of the robotic manipulator's trajectory is improved by 57% compared to one without. The tissue removal performance is also improved by 21% ( p < 0.05). The experiments show that virtual wall-based haptic guidance provides safer and more accurate tissue removal for single-port brain surgery.
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http://dx.doi.org/10.1177/0954411916676218DOI Listing
January 2017

An eco-friendly ultra-high performance ionic artificial muscle based on poly(2-acrylamido-2-methyl-1-propanesulfonic acid) and carboxylated bacterial cellulose.

J Mater Chem B 2016 Aug 7;4(29):5015-5024. Epub 2016 Jul 7.

School of Mechanical Engineering, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea.

Eco-friendly high-performance ionic artificial muscles have recently attracted enormous interest because of their applications in human friendly electronics including flexible haptic devices, wearable electronics, disposal or implantable biomedical devices, and biomimetic robots. Here, we report an eco-friendly ionic polymer actuator based on poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS), carboxylated bacterial cellulose (CBC), and an ionic liquid (IL) as a plasticizer, demonstrating ultra-high electromechanical deformation, quick response, and excellent durability. The proposed CBC-IL-PAMPS composite membrane exhibits an increased ionic conductivity, tensile strength, and specific capacitance of up to 32.5%, 44.9%, and 160%, respectively, thereby resulting in 4.5 times larger bending deformation than that of the CBC-IL actuator, all of which are due to the cross-linking and ionic interactions among the sulfonate functional groups of PAMPS, carboxylate functional groups of CBC, and the IL ([EMIM][BF]). The developed electro-chemo-mechanical CBC-IL-PAMPS actuator is a promising candidate for human friendly electronics such as artificial muscles, wearable devices, biomedical devices, and biomimetic robots due to its high actuation performance, low operating voltage, and fast response as well as durable operation.
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http://dx.doi.org/10.1039/c6tb01084aDOI Listing
August 2016

Hybrid-Actuating Macrophage-Based Microrobots for Active Cancer Therapy.

Sci Rep 2016 06 27;6:28717. Epub 2016 Jun 27.

School of Mechanical Engineering, Chonnam National University, Gwangju, Korea.

Using macrophage recruitment in tumors, we develop active, transportable, cancer theragnostic macrophage-based microrobots as vector to deliver therapeutic agents to tumor regions. The macrophage-based microrobots contain docetaxel (DTX)-loaded poly-lactic-co-glycolic-acid (PLGA) nanoparticles (NPs) for chemotherapy and Fe3O4 magnetic NPs (MNPs) for active targeting using an electromagnetic actuation (EMA) system. And, the macrophage-based microrobots are synthesized through the phagocytosis of the drug NPs and MNPs in the macrophages. The anticancer effects of the microrobots on tumor cell lines (CT-26 and 4T1) are evaluated in vitro by cytotoxic assay. In addition, the active tumor targeting by the EMA system and macrophage recruitment, and the chemotherapeutic effect of the microrobots are evaluated using three-dimensional (3D) tumor spheroids. The microrobots exhibited clear cytotoxicity toward tumor cells, with a low survivability rate (<50%). The 3D tumor spheroid assay showed that the microrobots demonstrated hybrid actuation through active tumor targeting by the EMA system and infiltration into the tumor spheroid by macrophage recruitment, resulting in tumor cell death caused by the delivered antitumor drug. Thus, the active, transportable, macrophage-based theragnostic microrobots can be considered to be biocompatible vectors for cancer therapy.
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http://dx.doi.org/10.1038/srep28717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921872PMC
June 2016

A novel curvature-controllable steerable needle for percutaneous intervention.

Proc Inst Mech Eng H 2016 Aug 19;230(8):727-38. Epub 2016 May 19.

Robot Research Initiative, School of Mechanical Engineering, Chonnam National University, Gwangju, Korea

Over the last few decades, flexible steerable robotic needles for percutaneous intervention have been the subject of significant interest. However, there still remain issues related to (a) steering the needle's direction with less damage to surrounding tissues and (b) increasing the needle's maximum curvature for better controllability. One widely used approach is to control the fixed-angled bevel-tip needle using a "duty-cycle" algorithm. While this algorithm has shown its applicability, it can potentially damage surrounding tissue, which has prevented the widespread adoption of this technology. This situation has motivated the development of a new steerable flexible needle that can change its curvature without axial rotation, while at the same time producing a larger curvature. In this article, we propose a novel curvature-controllable steerable needle. The proposed robotic needle consists of two parts: a cannula and a stylet with a bevel-tip. The curvature of the needle's path is controlled by a control offset, defined by the offset between the bevel-tip and the cannula. As a result, the necessity of rotating the whole needle's body is decreased. The duty-cycle algorithm is utilized to a limited degree to obtain a larger radius of curvature, which is similar to a straight path. The first prototype of 0.46 mm (outer diameter) was fabricated and tested with both in vitro gelatin phantom and ex vivo cow liver tissue. The maximum curvatures measured 0.008 mm(-1) in 6 wt% gelatin phantom, 0.0139 mm(-1) in 10 wt% gelatin phantom, and 0.0038 mm(-1) in cow liver. The experimental results show a linear relationship between the curvature and the control offset, which can be utilized for future implementation of this control algorithm.
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http://dx.doi.org/10.1177/0954411916648988DOI Listing
August 2016

Preparation of HIFU-triggered tumor-targeted hyaluronic acid micelles for controlled drug release and enhanced cellular uptake.

Colloids Surf B Biointerfaces 2016 Jul 9;143:27-36. Epub 2016 Mar 9.

School of Mechanical Engineering, Chonnam National University, 77 Yongbong-ro, Gwangju 500 757, Republic of Korea. Electronic address:

In this study, a novel type of high intensity focused ultrasound (HIFU)-triggered active tumor-targeting polymeric micelle was prepared and investigated for controlled drug release and enhanced cellular uptake. Amphiphilic hyaluronic acid (HA) conjugates were synthesized to form docetaxel loaded micelles in aqueous conditions with high encapsulation efficiencies of over 80%. The micelle sizes were limited to less than 150nm, and they varied slightly according to the encapsulated drug amount. Modifying the micellar surface modification with polyethylene glycol diamine successfully inhibited premature drug leakage at a certain level, and it can be expected to prolong the circulation time of the particles in blood. In addition, high-intensity focused ultrasound was introduced to control the release of docetaxel from micelles, to which the release behavior of a drug can be tuned. The in-vitro cell cytotoxicity of docetaxel-loaded micelles was verified against CT-26 and MDA-MB-231 cells. The IC50 values of drug-loaded micelles to CT-26 and MDA-MB-231 cells were 1230.2 and 870.9ng/mL, respectively. However, when exposed to HIFU, the values decreased significantly, to 181.9 and 114.3ng/mL, suggesting that HIFU can enhance cell cytotoxicity by triggering the release of a drug from the micelles. Furthermore, cellular uptake tests were conducted via the quantitative analysis of intracellular drug concentration within CT-26 (CD44 negative), MDA-MB-231 (CD44 positive), and MDA-MB-231 (CD44 blocked), and then imaged with coumarin-6 loaded micelles. The results verified that intracellular drug delivery can be enhanced efficiently via the CD44 receptor-mediated endocytosis of HA micelles. Moreover, HIFU enhanced the cellular uptake behavior by altering the permeability of the cell membrane. It was also able to aid with the extravasation of micelles into the interior of tumors, which will be explained in further research. Therefore, the present study demonstrates that the micelles prepared in this study can emerge as promising nanocarriers of chemotherapeutic agents for controlled drug release and tumor targeting in cancer treatment.
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http://dx.doi.org/10.1016/j.colsurfb.2016.03.019DOI Listing
July 2016

Penetration of an artificial arterial thromboembolism in a live animal using an intravascular therapeutic microrobot system.

Med Eng Phys 2016 Apr 5;38(4):403-10. Epub 2016 Feb 5.

School of Mechanical Engineering, Chonnam National University, Gwangju 61186, Korea. Electronic address:

The biomedical applications of wireless robots are an active area of study. In addition to moving to a target lesion, wireless locomotive robots can deliver a therapeutic drug for a specific disease. Thus, they hold great potential as therapeutic devices in blood vessel diseases, such as thrombi and occlusions, and in other diseases, such as cancer and inflammation. During a percutaneous coronary intervention (PCI), surgeons wear a heavy shielding cloth. However, they cannot escape severe radiation exposure owing to unstable shielding. They may also suffer from joint pains because of the weight of the shielding cloth. In addition, the catheters in PCIs are controlled by the surgeon's hand. Thus, they lack steering ability. A new intravascular therapeutic system is needed to address these problems in conventional PCIs. We developed an intravascular therapeutic microrobot system (ITMS) using an electromagnetic actuation (EMA) system with bi-plane X-ray devices that can remotely control a robot in blood vessels. Using this proposed ITMS, we demonstrated the locomotion of the robot in abdominal and iliac arteries of a live pig by the master-slave method. After producing an arterial thromboembolism in a live pig in a partial iliac artery, the robot moved to the target lesion and penetrated by specific motions (twisting and hammering) of the robot using the proposed ITMS. The results reveal that the proposed ITMS can realize stable locomotion (alignment and propulsion) of a robot in abdominal and iliac arteries of a live pig. This can be considered the first preclinical trial of the treatment of an artificial arterial thromboembolism by penetration of a blood clot.
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http://dx.doi.org/10.1016/j.medengphy.2016.01.001DOI Listing
April 2016

Preparation of Engineered Salmonella Typhimurium-Driven Hyaluronic-Acid-Based Microbeads with Both Chemotactic and Biological Targeting Towards Breast Cancer Cells for Enhanced Anticancer Therapy.

Adv Healthc Mater 2016 Jan 19;5(2):288-95. Epub 2015 Nov 19.

Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, 160 Baekseo-ro, Gwangju, 501-746, Republic of Korea.

In this study, a new type of targeted bacteriobots is prepared and investigated as a therapeutic strategy against solid tumors. Maleimide-functionalized hyaluronic acid (HA) polymer is synthesized and cross-linked with four-arm-thiolated polyethylene glycol (PEG-SH) to form HA microbeads with diameter of 8 μm through the Michael-type addition. Docetaxel (DTX)-loaded nanoparticles are encapsulated in HA-PEG microbeads and sustained in vitro drug-release pattern of the DTX from the HA-PEG microbeads is observed for up to 96 h. Dual-targeted bacteriobots are prepared using CD 44 receptor-targeted HA microbeads synthesized via microfluidics, followed by the attachment of the flagellar bacterium Salmonella typhimurium, which have been genetically engineered for tumor targeting, onto the surface of the HA microbeads by the specific interaction between streptavidin on the HA beads and biotin on the bacteria. After the attachment of bacteria, the bacteriobots show an average velocity of 0.72 μm s(-1) and high chemotactic migration velocity of 0.43 μm s(-1) towards 4T1 cells lysates. CD 44 receptor-specific cellular uptake is verified through flow cytometry analysis and confocal imaging, demonstrating enhanced intracellular uptake in CD 44 receptor positive tumor cells compared to normal cells. Therefore, the present study suggests that these bacteriobots have dual-tumor-targeting abilities displaying their potential for targeted anticancer therapy.
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http://dx.doi.org/10.1002/adhm.201500556DOI Listing
January 2016

Experimental and simulation studies on focused ultrasound triggered drug delivery.

Biotechnol Appl Biochem 2017 Jan 14;64(1):134-142. Epub 2016 Apr 14.

Department of Mechanical Engineering, Chonnam National University, Gwangju, Korea.

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.
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http://dx.doi.org/10.1002/bab.1453DOI Listing
January 2017

Modeling of chemotactic steering of bacteria-based microrobot using a population-scale approach.

Biomicrofluidics 2015 Sep 30;9(5):054116. Epub 2015 Sep 30.

School of Mechanical Engineering, Chonnam National University , 300, Yongbong-dong, Buk-gu, Gwangju, South Korea.

The bacteria-based microrobot (Bacteriobot) is one of the most effective vehicles for drug delivery systems. The bacteriobot consists of a microbead containing therapeutic drugs and bacteria as a sensor and an actuator that can target and guide the bacteriobot to its destination. Many researchers are developing bacteria-based microrobots and establishing the model. In spite of these efforts, a motility model for bacteriobots steered by chemotaxis remains elusive. Because bacterial movement is random and should be described using a stochastic model, bacterial response to the chemo-attractant is difficult to anticipate. In this research, we used a population-scale approach to overcome the main obstacle to the stochastic motion of single bacterium. Also known as Keller-Segel's equation in chemotaxis research, the population-scale approach is not new. It is a well-designed model derived from transport theory and adaptable to any chemotaxis experiment. In addition, we have considered the self-propelled Brownian motion of the bacteriobot in order to represent its stochastic properties. From this perspective, we have proposed a new numerical modelling method combining chemotaxis and Brownian motion to create a bacteriobot model steered by chemotaxis. To obtain modeling parameters, we executed motility analyses of microbeads and bacteriobots without chemotactic steering as well as chemotactic steering analysis of the bacteriobots. The resulting proposed model shows sound agreement with experimental data with a confidence level <0.01.
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http://dx.doi.org/10.1063/1.4932304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592439PMC
September 2015

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

Soft Matter 2016 Jan;12(1):246-54

Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.

Unlabelled: 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.
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http://dx.doi.org/10.1039/c5sm00707kDOI Listing
January 2016

Isolation and Characterization of a Monobody with a Fibronectin Domain III Scaffold That Specifically Binds EphA2.

PLoS One 2015 15;10(7):e0132976. Epub 2015 Jul 15.

Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.

Monobodies are binding scaffold proteins originating from a human fibronectin domain III (Fn3) scaffold that can be easily engineered with specificity and affinity. Human EphA2 (hEphA2) is an early detection marker protein for various tumors including lung, breast, and colon cancer. In this study, we isolated two hEphA2-specific monobodies (E1 and E10) by screening a yeast surface display library. They showed the same amino acid sequence except in the DE loop and had high affinity (~2 nM Kd) against hEphA2. E1 bound only hEphA2 and mEphA2, although it bound hEphA2 with an affinity 2-fold higher than that of mEphA2. However, E10 also bound the mEphA6 and mEphA8 homologs as well as hEphA2 and mEphA2. Thus, E1 but not E10 was highly specific for hEphA2. E1 specifically bound human cells and xenograft tumor tissues expressing hEphA on the cell surface. In vivo optical imaging showed strong targeting of Cy5.5-labeled E1 to mouse tumor tissue induced by PC3 cells, a human prostate cancer cell line that expresses a high level of hEphA2. In conclusion, the highly specific monobody E1 is useful as a hEphA2 probe candidate for in vivo diagnosis and therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132976PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503726PMC
May 2016

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

Biotechnol Bioeng 2015 Aug 5;112(8):1623-31. Epub 2015 May 5.

School of Mechanical Engineering, Chonnam National University, Gwangju, 500-757, Republic of Korea.

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.
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http://dx.doi.org/10.1002/bit.25555DOI Listing
August 2015

Shape memory alloy-based biopsy device for active locomotive intestinal capsule endoscope.

Proc Inst Mech Eng H 2015 Mar;229(3):255-63

School of Mechanical Engineering, Chonnam National University, Gwangju, Korea.

Recently, capsule endoscopes have been used for diagnosis in digestive organs. However, because a capsule endoscope does not have a locomotive function, its use has been limited to small tubular digestive organs, such as small intestine and esophagus. To address this problem, researchers have begun studying an active locomotive intestine capsule endoscope as a medical instrument for the whole gastrointestinal tract. We have developed a capsule endoscope with a small permanent magnet that is actuated by an electromagnetic actuation system, allowing active and flexible movement in the patient's gut environment. In addition, researchers have noted the need for a biopsy function in capsule endoscope for the definitive diagnosis of digestive diseases. Therefore, this paper proposes a novel robotic biopsy device for active locomotive intestine capsule endoscope. The proposed biopsy device has a sharp blade connected with a shape memory alloy actuator. The biopsy device measuring 12 mm in diameter and 3 mm in length was integrated into our capsule endoscope prototype, where the device's sharp blade was activated and exposed by the shape memory alloy actuator. Then the electromagnetic actuation system generated a specific motion of the capsule endoscope to extract the tissue sample from the intestines. The final biopsy sample tissue had a volume of about 6 mm(3), which is a sufficient amount for a histological analysis. Consequently, we proposed the working principle of the biopsy device and conducted an in-vitro biopsy test to verify the feasibility of the biopsy device integrated into the capsule endoscope prototype using the electro-magnetic actuation system.
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http://dx.doi.org/10.1177/0954411915576946DOI Listing
March 2015

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

Biotechnol Bioeng 2015 Apr 18;112(4):769-76. Epub 2014 Dec 18.

School of Mechanical Engineering, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju, 500-757, Republic of Korea.

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.
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http://dx.doi.org/10.1002/bit.25476DOI Listing
April 2015

Monocyte-based microrobot with chemotactic motility for tumor theragnosis.

Biotechnol Bioeng 2014 Oct 9;111(10):2132-8. Epub 2014 Jun 9.

School of Mechanical Engineering, Chonnam National University, Gwangju, 500-757, Republic of Korea.

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.
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http://dx.doi.org/10.1002/bit.25270DOI Listing
October 2014

Controlling uniformity of photopolymerized microscopic hydrogels.

Lab Chip 2014 May 14;14(9):1551-63. Epub 2014 Mar 14.

School of Mechanical Engineering, Chonnam National University, South Korea.

This paper studies hydrogels created by photopolymerization with a uniform beam of light. Under some conditions the density profiles of the resulting hydrogels were uniform cylinders, mirroring the illumination profiles. However, under other conditions, gels with hollow cylindrical shapes were formed. We studied the photopolymerization of poly-N-isopropylacrylamide (pNIPAAM), a hydrogel that has been widely used in tissue engineering and microfluidic applications, and examined how the size and uniformity of pNIPAAM microscopic gels can be controlled by varying parameters such as exposure time, exposure area, exposure intensity, monomer concentration, photoinitiator concentration and terminator concentration. A simplified reaction-diffusion model of the polymerization process was developed and was found to describe the experiment for a wide range of parameters. This general framework will guide attempts to establish optimal conditions for the construction of microscopic hydrogels using photolithography, which is a method that has found applications in fields such as microfluidics, drug delivery, cell and tissue culturing, and high resolution 3D printing.
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http://dx.doi.org/10.1039/c4lc00158cDOI Listing
May 2014

New paradigm for tumor theranostic methodology using bacteria-based microrobot.

Sci Rep 2013 Dec 2;3:3394. Epub 2013 Dec 2.

School of Mechanical Systems Engineering, Chonnam National University.

We propose a bacteria-based microrobot (bacteriobot) based on a new fusion paradigm for theranostic activities against solid tumors. We develop a bacteriobot using the strong attachment of bacteria to Cy5.5-coated polystyrene microbeads due to the high-affinity interaction between biotin and streptavidin. The chemotactic responses of the bacteria and the bacteriobots to the concentration gradients of lysates or spheroids of solid tumors can be detected as the migration of the bacteria and/or the bacteriobots out of the central region toward the side regions in a chemotactic microfluidic chamber. The bacteriobots showed higher migration velocity toward tumor cell lysates or spheroids than toward normal cells. In addition, when only the bacteriobots were injected to the CT-26 tumor mouse model, Cy5.5 signal was detected from the tumor site of the mouse model. In-vitro and in-vivo tests verified that the bacteriobots had chemotactic motility and tumor targeting ability. The new microrobot paradigm in which bacteria act as microactuators and microsensors to deliver microstructures to tumors can be considered a new theranostic methodology for targeting and treating solid tumors.
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http://dx.doi.org/10.1038/srep03394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3844944PMC
December 2013

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

Biotechnol Bioeng 2014 Jan 21;111(1):134-43. Epub 2013 Aug 21.

School of Mechanical Systems Engineering, Chonnam National University, Gwangju, 500-757, Korea.

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.
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http://dx.doi.org/10.1002/bit.25007DOI Listing
January 2014
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