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Koichiro Uto
Research Center for Functional Materials, National Institute for Materials Science (NIMS), Tsukuba, Japan

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Focus on trends in biomaterials in japan
Published: 24 June 2021 in Science and Technology of Advanced Materials
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We reports a novel thermally enhanced drug release system synthesized via a dynamic Diels-Alder (DA) reaction to develop chemotherapy for pancreatic cancer. The anticancer prodrug was designed by tethering gemcitabine (GEM) to poly(furfuryl methacrylate) (PFMA) via N-(3-maleimidopropionyloxy)succinimide as a linker by DA reaction (PFMA-L-GEM). The conversion rate of the DA reaction was found to be approximately 60% at room temperature for 120 h. The reversible deconstruction of the DA covalent bond in retro Diels-Alder (rDA) reaction was confirmed by proton nuclear magnetic resonance, and the reaction was significantly accelerated at 90 °C. A PFMA-LGEM film containing magnetic nanoparticles (MNPs) was prepared for thermally enhanced release of the drug via the rDA reaction. Drug release was initiated by heating MNPs by alternating magnetic field. This enables local heating within the film above the rDA reaction temperature while maintaining a constant surrounding medium temperature. The MNPs/PFMA-L-GEM film decreased the viability of pancreatic cancer cells by 49% over 24 h. Our results suggest that DA/rDA-based thermally enhanced drug release systems can serve as a local drug release platform and deliver the target drug within locally heated tissue, thereby improving the therapeutic efficiency and overcoming the side effects of conventional drugs used to treat pancreatic cancer. Graphical abstract

ACS Style

Nanami Fujisawa; Masato Takanohashi; Lili Chen; Koichiro Uto; Yoshitaka Matsumoto; Masayuki Takeuchi; Mitsuhiro Ebara. A Diels-Alder polymer platform for thermally enhanced drug release toward efficient local cancer chemotherapy. Science and Technology of Advanced Materials 2021, 22, 522 -531.

AMA Style

Nanami Fujisawa, Masato Takanohashi, Lili Chen, Koichiro Uto, Yoshitaka Matsumoto, Masayuki Takeuchi, Mitsuhiro Ebara. A Diels-Alder polymer platform for thermally enhanced drug release toward efficient local cancer chemotherapy. Science and Technology of Advanced Materials. 2021; 22 (1):522-531.

Chicago/Turabian Style

Nanami Fujisawa; Masato Takanohashi; Lili Chen; Koichiro Uto; Yoshitaka Matsumoto; Masayuki Takeuchi; Mitsuhiro Ebara. 2021. "A Diels-Alder polymer platform for thermally enhanced drug release toward efficient local cancer chemotherapy." Science and Technology of Advanced Materials 22, no. 1: 522-531.

Research article
Published: 28 March 2021 in BioMed Research International
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Hepatic fibrosis is a progressive disease with serious clinical complications that arise from abnormal propagation and activation of multiple inflammatory pathways. Nilotinib is an oral tyrosine kinase inhibitor with antifibrotic activity. Mesenchymal stem cells (MSCs) are blank cells and can differentiate into specific cell types. They have the potential to repair and regenerate cells. MSCs have a special paracrine fashion where they produce special exosomes, microvesicles, and cytokines like IL-6, transforming growth factor-beta (TGF-β), and HGF as well as hepatic stellate cell suppressors. This paracrine fashion can decrease collagen deposition, enhance antifibrotic, anti-inflammatory, and angiogenic activity in vitro and in vivo. In our study, the rat’s hepatic stellate cells (HSCs) in addition to different normal cell lines were treated with Nilotinib alone and in combination with liver mesenchymal stem cells conditioned medium (LMSCs-CM) for 24 h. Mono and combined therapy antifibrotic and cytotoxicity effects were evaluated using different parameters including α-SMA, cytochrome c, P53 expression, collagen deposition, DNA content, oxidative stress parameters, cell viability, and apoptosis by flow cytometry analysis. Our results showed that Nilotinib and LMSCs-CM in combination had a significantly potent antifibrotic and anti-inflammatory effect on activated hepatic stellate cells than Nilotinib alone; otherwise, this combination showed the best safety with minimal cytotoxicity on different normal cell lines.

ACS Style

Ahmed Nabil; Koichiro Uto; Faten Zahran; Reham Soliman; Ayman A. Hassan; Mohamed M. Elshemy; Islam S. Ali; Mitsuhiro Ebara; Gamal Shiha. The Potential Safe Antifibrotic Effect of Stem Cell Conditioned Medium and Nilotinib Combined Therapy by Selective Elimination of Rat Activated HSCs. BioMed Research International 2021, 2021, 1 -9.

AMA Style

Ahmed Nabil, Koichiro Uto, Faten Zahran, Reham Soliman, Ayman A. Hassan, Mohamed M. Elshemy, Islam S. Ali, Mitsuhiro Ebara, Gamal Shiha. The Potential Safe Antifibrotic Effect of Stem Cell Conditioned Medium and Nilotinib Combined Therapy by Selective Elimination of Rat Activated HSCs. BioMed Research International. 2021; 2021 ():1-9.

Chicago/Turabian Style

Ahmed Nabil; Koichiro Uto; Faten Zahran; Reham Soliman; Ayman A. Hassan; Mohamed M. Elshemy; Islam S. Ali; Mitsuhiro Ebara; Gamal Shiha. 2021. "The Potential Safe Antifibrotic Effect of Stem Cell Conditioned Medium and Nilotinib Combined Therapy by Selective Elimination of Rat Activated HSCs." BioMed Research International 2021, no. : 1-9.

Journal article
Published: 03 March 2021 in International Journal of Molecular Sciences
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This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.

ACS Style

Lili Chen; Nanami Fujisawa; Masato Takanohashi; Mazaya Najmina; Koichiro Uto; Mitsuhiro Ebara. A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy. International Journal of Molecular Sciences 2021, 22, 2542 .

AMA Style

Lili Chen, Nanami Fujisawa, Masato Takanohashi, Mazaya Najmina, Koichiro Uto, Mitsuhiro Ebara. A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy. International Journal of Molecular Sciences. 2021; 22 (5):2542.

Chicago/Turabian Style

Lili Chen; Nanami Fujisawa; Masato Takanohashi; Mazaya Najmina; Koichiro Uto; Mitsuhiro Ebara. 2021. "A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy." International Journal of Molecular Sciences 22, no. 5: 2542.

Research article
Published: 02 February 2021 in Oxidative Medicine and Cellular Longevity
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Type 2 diabetes mellitus (T2DM) is mainly characterized by insulin resistance and impaired insulin secretion, which cannot be reversed with existing therapeutic strategies. Using mesenchymal stem cells (MSCs), cell-based therapy has been demonstrated in displaying therapeutic effects in T2DM for their self-renewable, differentiation potential, and immunosuppressive properties and higher levels of angiogenic factors. Stem cell therapies are complicated and have a serious adverse effect including tumor formation and immunogenicity, while using mesenchymal stem cell-conditioned media (MSC-CM) significantly reduces stem cell risk, maintaining efficacy and showing significantly higher levels of growth factors, cytokines, and angiogenic factors that stimulate angiogenesis and promote fracture healing in diabetes. In the present study, we investigated the therapeutic potential of the liver and adipose MSC-CM in diabetic endothelial dysfunction compared with standard insulin therapy. Fifty adult male Sprague Dawley rats were divided equally into 5 groups as follows: control, diabetic, diabetic+insulin, diabetic+liver MSC-CM, and diabetic+adipose MSC-CM; all treatments continued for 4 weeks. Finally, we observed that liver MSC-CM therapy had the most apparent improvement in levels of blood glucose; HbA1c; AGEs; lipid panel (cholesterol, TG, LDL, HDL, and total lipids); renal function (urea, uric acid, creatinine, and total protein); liver function (AST, ALT, ALP, bilirubin, and albumin); CPK; C-peptide; HO-1; inflammatory markers including IL-6, TNF-α, and CRP; growth factors (liver and serum IGF-1); amylase; histopathological changes; pancreatic cell oxidative stress; and antioxidant markers (MDA, GSH, ROS, CAT, SOD, HO-1, and XO) toward the normal levels compared with insulin and adipose MSCs-CM. Moreover, both the liver and adipose MSC-CM relieved the hyperglycemic status by improving pancreatic islet β cell regeneration, promoting the conversion of alpha cells to beta cells, reducing insulin resistance, and protecting pancreatic tissues against oxidative stress-induced injury as well as possessing the ability to modulate immunity and angiogenesis. These results indicated that MSC-CM infusion has therapeutic effects in T2DM rats and may be a promising novel therapeutic target.

ACS Style

Mohamed M. Elshemy; Medhat Asem; Khaled S. Allemailem; Koichiro Uto; Mitsuhiro Ebara; Ahmed Nabil. Antioxidative Capacity of Liver- and Adipose-Derived Mesenchymal Stem Cell-Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats. Oxidative Medicine and Cellular Longevity 2021, 2021, 1 -11.

AMA Style

Mohamed M. Elshemy, Medhat Asem, Khaled S. Allemailem, Koichiro Uto, Mitsuhiro Ebara, Ahmed Nabil. Antioxidative Capacity of Liver- and Adipose-Derived Mesenchymal Stem Cell-Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats. Oxidative Medicine and Cellular Longevity. 2021; 2021 ():1-11.

Chicago/Turabian Style

Mohamed M. Elshemy; Medhat Asem; Khaled S. Allemailem; Koichiro Uto; Mitsuhiro Ebara; Ahmed Nabil. 2021. "Antioxidative Capacity of Liver- and Adipose-Derived Mesenchymal Stem Cell-Conditioned Media and Their Applicability in Treatment of Type 2 Diabetic Rats." Oxidative Medicine and Cellular Longevity 2021, no. : 1-11.

Research article
Published: 29 May 2020 in Oxidative Medicine and Cellular Longevity
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Cancer, as a group, represents the most important cause of death worldwide. Unfortunately, the available therapeutic approaches of cancer including surgery, chemotherapy, radiotherapy, and immunotherapy are unsatisfactory and represent a great challenge as many patients have cancer recurrence and severe side effects. Methotrexate (MTX) is a well-established (antineoplastic or cytotoxic) chemotherapy and immunosuppressant drug used to treat different types of cancer, but its usage requires high doses causing severe side effects. Therefore, we need a novel drug with high antitumor efficacy in addition to safety. The aim of this study was the evaluation of the antitumor efficacy of zinc oxide nanoparticle (ZnO-NPs) and sorafenib alone or in combination on solid Ehrlich carcinoma (SEC) in mice. Sixty adult female Swiss-albino mice were divided equally into 6 groups as follows: control, SEC, MTX, ZnO-NPs, sorafenib, and ZnO-NPs+sorafenib; all treatments continued for 4 weeks. ZnO-NPs were characterized by TEM, zeta potential, and SEM mapping. Data showed that ZnO-NPs synergized with sorafenib as a combination therapy to execute more effective and safer anticancer activity compared to monotherapy as showed by a significant reduction (P<0.001) in tumor weight, tumor cell viability, and cancer tissue glutathione amount as well as by significant increase (P<0.001) in tumor growth inhibition rate, DNA fragmentation, reactive oxygen species generation, the release of cytochrome c, and expression of the apoptotic gene caspase-3 in the tumor tissues with minimal changes in the liver, renal, and hematological parameters. Therefore, we suggest that ZnO-NPs might be a safe candidate in combination with sorafenib as a more potent anticancer. The safety of this combined treatment may allow its use in clinical trials.

ACS Style

Ahmed Nabil; Mohamed M. Elshemy; Medhat Asem; Marwa Abdel-Motaal; Heba F. Gomaa; Faten Zahran; Koichiro Uto; Mitsuhiro Ebara. Zinc Oxide Nanoparticle Synergizes Sorafenib Anticancer Efficacy with Minimizing Its Cytotoxicity. Oxidative Medicine and Cellular Longevity 2020, 2020, 1 -11.

AMA Style

Ahmed Nabil, Mohamed M. Elshemy, Medhat Asem, Marwa Abdel-Motaal, Heba F. Gomaa, Faten Zahran, Koichiro Uto, Mitsuhiro Ebara. Zinc Oxide Nanoparticle Synergizes Sorafenib Anticancer Efficacy with Minimizing Its Cytotoxicity. Oxidative Medicine and Cellular Longevity. 2020; 2020 ():1-11.

Chicago/Turabian Style

Ahmed Nabil; Mohamed M. Elshemy; Medhat Asem; Marwa Abdel-Motaal; Heba F. Gomaa; Faten Zahran; Koichiro Uto; Mitsuhiro Ebara. 2020. "Zinc Oxide Nanoparticle Synergizes Sorafenib Anticancer Efficacy with Minimizing Its Cytotoxicity." Oxidative Medicine and Cellular Longevity 2020, no. : 1-11.

Journal article
Published: 22 April 2020 in Polymer Journal
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Although the roles of elastic components in breast cancer progression have been widely studied, the importance of matrix dissipative elements in regulating breast cancer behavior is still poorly understood. In this study, we designed viscosity-tunable fluidic substrates to investigate the effects of matrix viscosity on the alteration of breast cancer cellular fate using a hydrophobic molten polymer of poly(ε-caprolactone-co-D,L-lactide) [P(CL-co-DLLA)] with different levels of fluidity. The high- and low-fluidity substrates used in this study were shown to behave as viscoelastic liquids at physiological temperature. A nonmetastatic breast cancer cell line (MCF-7) was cultured at the interface of the fibronectin-coated substrate, and its behavior towards the substrate fluidity level was thoroughly characterized. Despite fibronectin-mediated cell-substrate interactions, MCF-7 cells show sensitivity to substrate fluidity levels by forming types aggregates of different sizes and structures over time. Accordingly, MCF-7 cells were undergoing senescence on fluidic substrates, as shown by high metabolic activity over time, suppressed proliferation ability, and positive expression of senescence markers. Moreover, senescence implies more resistance towards anticancer drug treatment. This indicates that a fluidic substrate, as a two-dimensional synthetic matrix system, could demonstrate the importance of mechanical cues in redefining cellular function and cellular fate by changing the viscosity of the pure substrate.

ACS Style

Mazaya Najmina; Koichiro Uto; Mitsuhiro Ebara. Fluidic substrate as a tool to probe breast cancer cell adaptive behavior in response to fluidity level. Polymer Journal 2020, 52, 985 -995.

AMA Style

Mazaya Najmina, Koichiro Uto, Mitsuhiro Ebara. Fluidic substrate as a tool to probe breast cancer cell adaptive behavior in response to fluidity level. Polymer Journal. 2020; 52 (8):985-995.

Chicago/Turabian Style

Mazaya Najmina; Koichiro Uto; Mitsuhiro Ebara. 2020. "Fluidic substrate as a tool to probe breast cancer cell adaptive behavior in response to fluidity level." Polymer Journal 52, no. 8: 985-995.

Journal article
Published: 17 April 2020 in Polymers
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Vital pulp therapy is an important endodontic treatment. Strategies using growth factors and biological molecules are effective in developing pulp capping materials based on wound healing by the dentin-pulp complex. Our group developed biodegradable viscoelastic polymer materials for tissue-engineered medical devices. The polymer contents help overcome the poor fracture toughness of hydroxyapatite (HAp)-facilitated osteogenic differentiation of pulp cells. However, the composition of this novel polymer remained unclear. This study evaluated a novel polymer composite, P(CL-co-DLLA) and HAp, as a direct pulp capping carrier for biological molecules. The biocompatibility of the novel polymer composite was evaluated by determining the cytotoxicity and proliferation of human dental stem cells in vitro. The novel polymer composite with BMP-2, which reportedly induced tertiary dentin, was tested as a direct pulp capping material in a rat model. Cytotoxicity and proliferation assays revealed that the biocompatibility of the novel polymer composite was similar to that of the control. The novel polymer composite with BMP-2-induced tertiary dentin, similar to hydraulic calcium-silicate cement, in the direct pulp capping model. The BMP-2 composite upregulated wound healing-related gene expression compared to the novel polymer composite alone. Therefore, we suggest that novel polymer composites could be effective carriers for pulp capping.

ACS Style

Motoki Okamoto; Sayako Matsumoto; Ayato Sugiyama; Kei Kanie; Masakatsu Watanabe; Hailing Huang; Manahil Ali; Yuki Ito; Jiro Miura; Yujiro Hirose; Koichiro Uto; Mitsuhiro Ebara; Ryuji Kato; Aika Yamawaki-Ogata; Yuji Narita; Shigetada Kawabata; Yusuke Takahashi; Mikako Hayashi. Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair. Polymers 2020, 12, 937 .

AMA Style

Motoki Okamoto, Sayako Matsumoto, Ayato Sugiyama, Kei Kanie, Masakatsu Watanabe, Hailing Huang, Manahil Ali, Yuki Ito, Jiro Miura, Yujiro Hirose, Koichiro Uto, Mitsuhiro Ebara, Ryuji Kato, Aika Yamawaki-Ogata, Yuji Narita, Shigetada Kawabata, Yusuke Takahashi, Mikako Hayashi. Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair. Polymers. 2020; 12 (4):937.

Chicago/Turabian Style

Motoki Okamoto; Sayako Matsumoto; Ayato Sugiyama; Kei Kanie; Masakatsu Watanabe; Hailing Huang; Manahil Ali; Yuki Ito; Jiro Miura; Yujiro Hirose; Koichiro Uto; Mitsuhiro Ebara; Ryuji Kato; Aika Yamawaki-Ogata; Yuji Narita; Shigetada Kawabata; Yusuke Takahashi; Mikako Hayashi. 2020. "Performance of a Biodegradable Composite with Hydroxyapatite as a Scaffold in Pulp Tissue Repair." Polymers 12, no. 4: 937.

Journal article
Published: 04 March 2020 in International Journal of Molecular Sciences
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Background: We propose the potential studies on material fluidity to induce epithelial to mesenchymal transition (EMT) in MCF-7 cells. In this study, we examined for the first time the effect of material fluidity on EMT using poly(ε-caprolactone-co-D,L-lactide) (P(CL-co-DLLA)) with tunable elasticity and fluidity. Methods: The fluidity was altered by chemically crosslinking the polymer networks. The crosslinked P(CL-co-DLLA) substrate showed a solid-like property with a stiffness of 261 kPa, while the non-crosslinked P(CL-co-DLLA) substrate of 100 units (high fluidity) and 500 units (low fluidity) existed in a quasi-liquid state with loss modulus of 33 kPa and 30.8 kPa, respectively, and storage modulus of 10.8 kPa and 20.1 kPa, respectively. Results: We observed that MCF-7 cells on low fluidic substrates decreased the expression of E-cadherin, an epithelial marker, and increased expression of vimentin, a mesenchymal marker. This showed that the cells lose their epithelial phenotype and gain a mesenchymal property. On the other hand, MCF-7 cells on high fluidic substrates maintained their epithelial phenotype, suggesting that the cells did not undergo EMT. Conclusion: Considering these results as the fundamental information for material fluidity induced EMT, our system could be used to regulate the degree of EMT by turning the fluidity of the material.

ACS Style

Sharmy Saimon Mano; Koichiro Uto; Mitsuhiro Ebara. Fluidity of Poly (ε-Caprolactone)-Based Material Induces Epithelial-to-Mesenchymal Transition. International Journal of Molecular Sciences 2020, 21, 1757 .

AMA Style

Sharmy Saimon Mano, Koichiro Uto, Mitsuhiro Ebara. Fluidity of Poly (ε-Caprolactone)-Based Material Induces Epithelial-to-Mesenchymal Transition. International Journal of Molecular Sciences. 2020; 21 (5):1757.

Chicago/Turabian Style

Sharmy Saimon Mano; Koichiro Uto; Mitsuhiro Ebara. 2020. "Fluidity of Poly (ε-Caprolactone)-Based Material Induces Epithelial-to-Mesenchymal Transition." International Journal of Molecular Sciences 21, no. 5: 1757.

Communication
Published: 09 December 2019 in Advanced Materials
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There is a growing interest in the development of dynamic adaptive biomaterials for regulation of cellular functions. However, existing materials are limited to two‐state switching of the presentation and removal of cell‐adhesive bioactive motifs that cannot emulate the native extracellular matrix (ECM) in vivo with continuously adjustable characteristics. Here, tunable adaptive materials composed of a protein monolayer assembled at a liquid–liquid interface are demonstrated, which adapt dynamically to cell traction forces. An ultrastructure transition from protein monolayer to hierarchical fiber occurs through interfacial jamming. Elongated fibronectin fibers promote formation of elongated focal adhesion structures, increase focal adhesion kinase activation, and enhance neuronal differentiation of stem cells. Cell traction force results in spatial rearrangement of ECM proteins, which feeds back to alter stem cell fate. The reported biomimetic adaptive liquid interface enables dynamic control of stem cell behavior and has potential translational applications.

ACS Style

Xiaofang Jia; Kosuke Minami; Koichiro Uto; Alice Chinghsuan Chang; Jonathan P. Hill; Jun Nakanishi; Katsuhiko Ariga. Adaptive Liquid Interfacially Assembled Protein Nanosheets for Guiding Mesenchymal Stem Cell Fate. Advanced Materials 2019, 32, e1905942 .

AMA Style

Xiaofang Jia, Kosuke Minami, Koichiro Uto, Alice Chinghsuan Chang, Jonathan P. Hill, Jun Nakanishi, Katsuhiko Ariga. Adaptive Liquid Interfacially Assembled Protein Nanosheets for Guiding Mesenchymal Stem Cell Fate. Advanced Materials. 2019; 32 (4):e1905942.

Chicago/Turabian Style

Xiaofang Jia; Kosuke Minami; Koichiro Uto; Alice Chinghsuan Chang; Jonathan P. Hill; Jun Nakanishi; Katsuhiko Ariga. 2019. "Adaptive Liquid Interfacially Assembled Protein Nanosheets for Guiding Mesenchymal Stem Cell Fate." Advanced Materials 32, no. 4: e1905942.

Rapid communication
Published: 05 July 2019 in Chemistry Letters
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Control of biodegradability of slow degradable poly(ε-caprolactone) (PCL) is a key challenge in biomedical fields. In this study, the degradation control of electrospun PCL fiber meshes was successfully achieved by simply blending polymers with high- and low-molecular weight without incorporating non-PCL components. Although lower molecular weight polymers are generally difficult to be electrospun into nanofibers, our polyblends strategy enabled to electrospun low-PCL by blending it with high-one without sacrificing accelerated degradation speed.

ACS Style

Eri Niiyama; Koichiro Uto; Mitsuhiro Ebara. Electrospun PCL-PCL Polyblend Nanofibers with High- and Low-molecular Weight for Controlled Degradation. Chemistry Letters 2019, 48, 623 -626.

AMA Style

Eri Niiyama, Koichiro Uto, Mitsuhiro Ebara. Electrospun PCL-PCL Polyblend Nanofibers with High- and Low-molecular Weight for Controlled Degradation. Chemistry Letters. 2019; 48 (7):623-626.

Chicago/Turabian Style

Eri Niiyama; Koichiro Uto; Mitsuhiro Ebara. 2019. "Electrospun PCL-PCL Polyblend Nanofibers with High- and Low-molecular Weight for Controlled Degradation." Chemistry Letters 48, no. 7: 623-626.

Journal article
Published: 01 May 2019 in Fibers
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Excellent water-absorbing nanofiber meshes were developed as a potential material for removing excess fluids from the blood of chronic renal failure patients toward a wearable blood purification system without requiring specialized equipment. The nanofiber meshes were successfully fabricated from poly(acrylic acid) (PAA) under various applied voltages by appropriately setting the electrospinning conditions. The electrospun PAA nanofibers were thermally crosslinked via heat treatment and then neutralized from their carboxylic acid form (PAA) to a sodium carboxylate form poly(sodium acrylate) (PSA). The PSA nanofiber meshes exhibited a specific surface area 393 times that of the PSA film. The PSA fiber meshes showed a much faster and higher swelling than its corresponding film, owing to the higher capillary forces from the fibers in addition to the water absorption of the PSA gel itself. The proposed PSA fibers have the potential to be utilized in a new approach to remove excess water from the bloodstream without requiring specialized equipment.

ACS Style

Mirei Tsuge; Kanoko Takahashi; Rio Kurimoto; Ailifeire Fulati; Koichiro Uto; Akihiko Kikuchi; Mitsuhiro Ebara. Fabrication of Water Absorbing Nanofiber Meshes toward an Efficient Removal of Excess Water from Kidney Failure Patients. Fibers 2019, 7, 39 .

AMA Style

Mirei Tsuge, Kanoko Takahashi, Rio Kurimoto, Ailifeire Fulati, Koichiro Uto, Akihiko Kikuchi, Mitsuhiro Ebara. Fabrication of Water Absorbing Nanofiber Meshes toward an Efficient Removal of Excess Water from Kidney Failure Patients. Fibers. 2019; 7 (5):39.

Chicago/Turabian Style

Mirei Tsuge; Kanoko Takahashi; Rio Kurimoto; Ailifeire Fulati; Koichiro Uto; Akihiko Kikuchi; Mitsuhiro Ebara. 2019. "Fabrication of Water Absorbing Nanofiber Meshes toward an Efficient Removal of Excess Water from Kidney Failure Patients." Fibers 7, no. 5: 39.

Full paper
Published: 29 April 2019 in Advanced Healthcare Materials
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Effective cancer therapy can be achieved by designing a smart nanofiber system with the combination of chemotherapy and hyperthermia. This study demonstrates the in vivo antitumor effect of a nanofiber mesh that can deliver heat and antitumor drug in a controlled manner. The mesh is composed of biodegradable poly(ε‐caprolactone) (PCL) with paclitaxel (PTX) and magnetic nanoparticles (MNPs). The PCL mesh releases PTX slowly for at least 6 weeks when tested in vitro. The prolonged therapeutic effect is observed in vivo as a continuous release of medication from the mesh over an extended period of time compared with direct injection of PTX into the tumor site. In addition, the synergistic anticancer effect is achieved upon excitation of the mesh with an alternating magnetic field because the MNPs within the nanofiber generate localized heat which causes heat‐induced cell killing as well as enhanced chemotherapeutic effect of PTX. Based on these results, the smart nanofiber system may be very promising for cancer therapeutics in the future and may provide knowledge for new development of localized drug delivery.

ACS Style

Eri Niiyama; Koichiro Uto; Chun Man Lee; Kazuma Sakura; Mitsuhiro Ebara. Hyperthermia Nanofiber Platform Synergized by Sustained Release of Paclitaxel to Improve Antitumor Efficiency. Advanced Healthcare Materials 2019, 8, e1900102 .

AMA Style

Eri Niiyama, Koichiro Uto, Chun Man Lee, Kazuma Sakura, Mitsuhiro Ebara. Hyperthermia Nanofiber Platform Synergized by Sustained Release of Paclitaxel to Improve Antitumor Efficiency. Advanced Healthcare Materials. 2019; 8 (13):e1900102.

Chicago/Turabian Style

Eri Niiyama; Koichiro Uto; Chun Man Lee; Kazuma Sakura; Mitsuhiro Ebara. 2019. "Hyperthermia Nanofiber Platform Synergized by Sustained Release of Paclitaxel to Improve Antitumor Efficiency." Advanced Healthcare Materials 8, no. 13: e1900102.

Focus on bio inspired nanomaterials
Published: 01 March 2019 in Science and Technology of Advanced Materials
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Combining immunotherapeutic and radiotherapeutic technique has recently attracted much attention for advancing cancer treatment. If boron-incorporated hemagglutinating virus of Japan-envelope (HVJ-E) having high membrane fusion ability can be used as a boron delivery agent in boron neutron capture therapy (BNCT), a radical synergistic improvement of boron accumulation efficiency into tumor cells and antitumor immunity may be induced. In this study, we aimed to develop novel boron-containing biocompatible polymers modified onto HVJ-E surfaces. The copolymer consisting of 2-methacryloyloxyethyl phosphorylcholine (MPC) and methacrylamide benzoxaborole (MAAmBO), poly[MPC-co-MAAmBO], was successfully synthesized by using a simple free radical polymerization. The molecular structures and molecular weight of the poly[MPC-co-MAAmBO] copolymer were characterized by nuclear magnetic resonance and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, respectively. The poly[MPC-co-MAAmBO] was coated onto the HVJ-E surface via the chemical bonding between the MAAmBO moiety and the sugar moiety of HVJ-E. DLS, AFM, UV-Vis, and fluorescence measurements clarified that the size of the poly[MPC-co-MAAmBO]-coated HVJ-E, HVJ-E/p[MPC-MAAmBO], to be about 130 ~ 150 nm in diameter, and that the polymer having 9.82 × 106 ~ 7 boron atoms was steadily coated on a single HVJ-E particle. Moreover, cellular uptake of poly[MPC-co-MAAmBO] could be demonstrated without cytotoxicity, and the hemolysis could be successfully suppressed by 20%. These results indicate that the HVJ-E/p[MPC-MAAmBO] may be used as boron nanocarriers in a combination of immunotherapy with BNCT. Graphical Abstract

ACS Style

Shuichiro Yoneoka; Yasuhiro Nakagawa; Koichiro Uto; Kazuma Sakura; Takehiko Tsukahara; Mitsuhiro Ebara. Boron-incorporating hemagglutinating virus of Japan envelope (HVJ-E) nanomaterial in boron neutron capture therapy. Science and Technology of Advanced Materials 2019, 20, 291 -304.

AMA Style

Shuichiro Yoneoka, Yasuhiro Nakagawa, Koichiro Uto, Kazuma Sakura, Takehiko Tsukahara, Mitsuhiro Ebara. Boron-incorporating hemagglutinating virus of Japan envelope (HVJ-E) nanomaterial in boron neutron capture therapy. Science and Technology of Advanced Materials. 2019; 20 (1):291-304.

Chicago/Turabian Style

Shuichiro Yoneoka; Yasuhiro Nakagawa; Koichiro Uto; Kazuma Sakura; Takehiko Tsukahara; Mitsuhiro Ebara. 2019. "Boron-incorporating hemagglutinating virus of Japan envelope (HVJ-E) nanomaterial in boron neutron capture therapy." Science and Technology of Advanced Materials 20, no. 1: 291-304.

Journal article
Published: 01 March 2019 in Fibers
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In this work we report the rational design of temperature-responsive nanofiber meshes with shape-memory properties. Meshes were fabricated by electrospinning poly(ε-caprolactone) (PCL)-based polyurethane with varying ratios of soft (PCL diol) and hard [hexamethylene diisocyanate (HDI)/1,4-butanediol (BD)] segments. By altering the PCL diol:HDI:BD molar ratio both shape-memory properties and mechanical properties could be readily turned and modulated. Though mechanical properties improved by increasing the hard to soft segment ratio, optimal shape-memory properties were obtained using a PCL/HDI/BD molar ratio of 1:4:3. Microscopically, the original nanofibrous structure could be deformed into and maintained in a temporary shape and later recover its original structure upon reheating. Even when deformed by 400%, a recovery rate of >89% was observed. Implementation of these shape memory nanofiber meshes as cell culture platforms revealed the unique ability to alter human mesenchymal stem cell alignment and orientation. Due to their biocompatible nature, temperature-responsivity, and ability to control cell alignment, we believe that these meshes may demonstrate great promise as biomedical applications.

ACS Style

Eri Niiyama; Kanta Tanabe; Koichiro Uto; Akihiko Kikuchi; Mitsuhiro Ebara. Shape-Memory Nanofiber Meshes with Programmable Cell Orientation. Fibers 2019, 7, 20 .

AMA Style

Eri Niiyama, Kanta Tanabe, Koichiro Uto, Akihiko Kikuchi, Mitsuhiro Ebara. Shape-Memory Nanofiber Meshes with Programmable Cell Orientation. Fibers. 2019; 7 (3):20.

Chicago/Turabian Style

Eri Niiyama; Kanta Tanabe; Koichiro Uto; Akihiko Kikuchi; Mitsuhiro Ebara. 2019. "Shape-Memory Nanofiber Meshes with Programmable Cell Orientation." Fibers 7, no. 3: 20.

Communication
Published: 09 January 2019 in Small
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Mechanical cues of cellular microenvironments can modulate cell functions including cell spreading and differentiation. Most studies of cellular functions are performed using a solid substrate, and it is thought that cells cannot spread on fluid substrates because of rapid relaxation, which cannot resist against actomyosin‐based cell contractility. Here, the spreading and growth of anchorage‐dependent cells such as human mesenchymal stem cells at the liquid interface between a perfluorocarbon fluid and the culture medium are observed. It is demonstrated that a monomolecular protein nanosheet self‐assembled at a fluid interface is sufficiently rigid to support cell spreading without additional treatment. Fine tuning of the packing of these proteins at the liquid interface permits tailoring of the mechanics of the protein layer, ultimately allowing for the regulation of cell spreading. The greater stiffness of the protein nanosheets triggers cell spreading, adhesion growth, and yes‐associated protein nuclear translocation. Cell behavior at the fluid interface is explained within the framework of the molecular clutch model. In addition, the freestanding ultrathin protein nanosheets are extremely flexible, easily deformed, and perceived by cells as being much softer. The findings are expected to provide a new perspective for insights into cell–material interactions.

ACS Style

Xiaofang Jia; Kosuke Minami; Koichiro Uto; Alice Chinghsuan Chang; Jonathan Hill; Takeshi Ueki; Jun Nakanishi; Katsuhiko Ariga. Modulation of Mesenchymal Stem Cells Mechanosensing at Fluid Interfaces by Tailored Self‐Assembled Protein Monolayers. Small 2019, 15, e1804640 .

AMA Style

Xiaofang Jia, Kosuke Minami, Koichiro Uto, Alice Chinghsuan Chang, Jonathan Hill, Takeshi Ueki, Jun Nakanishi, Katsuhiko Ariga. Modulation of Mesenchymal Stem Cells Mechanosensing at Fluid Interfaces by Tailored Self‐Assembled Protein Monolayers. Small. 2019; 15 (5):e1804640.

Chicago/Turabian Style

Xiaofang Jia; Kosuke Minami; Koichiro Uto; Alice Chinghsuan Chang; Jonathan Hill; Takeshi Ueki; Jun Nakanishi; Katsuhiko Ariga. 2019. "Modulation of Mesenchymal Stem Cells Mechanosensing at Fluid Interfaces by Tailored Self‐Assembled Protein Monolayers." Small 15, no. 5: e1804640.

Journal article
Published: 13 September 2018 in Polymers
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We have developed a smart anti-cancer fiber mesh that is able to control tumor-killing activity against lung adenocarcinoma precisely. The mesh is capable of carrying large loads of chemotherapeutic drug, paclitaxel (PTX), as well as magnetic nanoparticles (MNPs). The mesh generates heat when the loaded MNPs are activated in an alternating magnetic field (AMF). The mesh is thermo-responsive, so the heat generated can be also used to trigger PTX release from the mesh. An electrospinning method was employed to fabricate the mesh using a copolymer of N-isopropylacrylamide and N-hydroxymethylacrylamide, the phase transition temperature of which was adjusted to the mild-hyperthermia temperature range around 43 °C. In vitro anti-tumor studies demonstrated that both MNP- and PTX-loaded mesh killed about 66% of cells, whereas only PTX-loaded mesh killed about 43% of cells. In a mouse lung cancer model, the thermo-chemotherapy combo displayed enhanced anti-tumor activity and the systemic toxic effects on mice were eliminated due to local release of the chemotherapeutic agents. The proposed fiber system might provide a blueprint to guide the design of the next generation of local drug delivery systems for safe and effective cancer treatment.

ACS Style

Eri Niiyama; Koichiro Uto; Chun Man Lee; Kazuma Sakura; Mitsuhiro Ebara. Alternating Magnetic Field-Triggered Switchable Nanofiber Mesh for Cancer Thermo-Chemotherapy. Polymers 2018, 10, 1018 .

AMA Style

Eri Niiyama, Koichiro Uto, Chun Man Lee, Kazuma Sakura, Mitsuhiro Ebara. Alternating Magnetic Field-Triggered Switchable Nanofiber Mesh for Cancer Thermo-Chemotherapy. Polymers. 2018; 10 (9):1018.

Chicago/Turabian Style

Eri Niiyama; Koichiro Uto; Chun Man Lee; Kazuma Sakura; Mitsuhiro Ebara. 2018. "Alternating Magnetic Field-Triggered Switchable Nanofiber Mesh for Cancer Thermo-Chemotherapy." Polymers 10, no. 9: 1018.

Review article
Published: 14 August 2018 in Biosensors and Bioelectronics
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Biomaterials have gained increasing attention in fabrication of a variety of flexible electronics due to their tunable solubility, robust mechanical property, multi-active binding sites, and excellent biocompatible and biodegradable characterization as well. Here, we review the recent progress of bio-based materials in flexible sensors, mainly describe nature biomaterials (silk fibroin, cellulose and chitin) and chemical-synthesized biomaterials as well as their applications in health monitors, biosensor, human-machine interactions (HMIs) and more, and highlight the current opportunities and challenges that lay ahead in mounting numbers of academia and industry. Furthermore, we expect this review could contribute to unveiling the potentials of developing outstanding and eco-friendly sensors with biomaterials by utilization of printing techniques.

ACS Style

Qingqing Sun; Binbin Qian; Koichiro Uto; Jinzhou Chen; Xuying Liu; Takeo Minari. Functional biomaterials towards flexible electronics and sensors. Biosensors and Bioelectronics 2018, 119, 237 -251.

AMA Style

Qingqing Sun, Binbin Qian, Koichiro Uto, Jinzhou Chen, Xuying Liu, Takeo Minari. Functional biomaterials towards flexible electronics and sensors. Biosensors and Bioelectronics. 2018; 119 ():237-251.

Chicago/Turabian Style

Qingqing Sun; Binbin Qian; Koichiro Uto; Jinzhou Chen; Xuying Liu; Takeo Minari. 2018. "Functional biomaterials towards flexible electronics and sensors." Biosensors and Bioelectronics 119, no. : 237-251.

Journals
Published: 09 March 2018 in Biomaterials Science
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Temporal elasticity and roughness modulation with temperature-responsive poly(ε-caprolactone) induced the alternation of hepatocellular function dynamically.

ACS Style

Koichiro Uto; Takao Aoyagi; Cole A DeFOREST; Mitsuhiro Ebara. Dynamic alterations of hepatocellular function by on-demand elasticity and roughness modulation. Biomaterials Science 2018, 6, 1002 -1006.

AMA Style

Koichiro Uto, Takao Aoyagi, Cole A DeFOREST, Mitsuhiro Ebara. Dynamic alterations of hepatocellular function by on-demand elasticity and roughness modulation. Biomaterials Science. 2018; 6 (5):1002-1006.

Chicago/Turabian Style

Koichiro Uto; Takao Aoyagi; Cole A DeFOREST; Mitsuhiro Ebara. 2018. "Dynamic alterations of hepatocellular function by on-demand elasticity and roughness modulation." Biomaterials Science 6, no. 5: 1002-1006.

Journal article
Published: 26 February 2018 in Polymer Journal
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In this study, a convenient method to synthesize cationic macromonomers containing branched poly(ε-caprolactone) (PCL) was developed, and stable materials were derived by photo-cross-linking reactions. In fact, a bromomethyl-terminated modification was carried out at the hydroxyl end groups of the starting PCL; then, the terminal groups reacted with 2,2′-dimethylaminoethyl methacrylate to afford the objective macromonomers, which had N,N′-dimethylmethacrylamino groups at the chain ends. The resulting PCL-based materials were cross-linked by UV light irradiation and were stable against exposure to organic solvents and heating above the softening points. The surface properties of the cationic, PCL, cross-linked membrane were evaluated by measuring the zeta potentials and performing anionic dye adsorption tests using Acid Red 87. As expected, the cationic, PCL, cross-linked membrane surfaces showed a positive charge and greater dye adsorption than the naked PCL, which depended on the cationic contents and temperature. Over the softening point, the positive charge steeply increased. The morphologies of adhered human mesenchymal stem cells on the PCL materials with lower cationic contents were preliminarily observed and shown to be well dispersed. The PCL-based materials in this study could enhance cell interaction and be useful for scaffold or mechanobiology studies.

ACS Style

Kohei Iwamatsu; Koichiro Uto; Yuta Takeuchi; Toru Hoshi; Takao Aoyagi. Preparation of temperature-responsive, cationized, poly(ε-caprolactone)-based, cross-linked materials by a macromonomer design and positive charge control on the surface. Polymer Journal 2018, 50, 447 -454.

AMA Style

Kohei Iwamatsu, Koichiro Uto, Yuta Takeuchi, Toru Hoshi, Takao Aoyagi. Preparation of temperature-responsive, cationized, poly(ε-caprolactone)-based, cross-linked materials by a macromonomer design and positive charge control on the surface. Polymer Journal. 2018; 50 (6):447-454.

Chicago/Turabian Style

Kohei Iwamatsu; Koichiro Uto; Yuta Takeuchi; Toru Hoshi; Takao Aoyagi. 2018. "Preparation of temperature-responsive, cationized, poly(ε-caprolactone)-based, cross-linked materials by a macromonomer design and positive charge control on the surface." Polymer Journal 50, no. 6: 447-454.

Communication
Published: 22 November 2017 in Applied Sciences
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Shape-memory polymers have seen tremendous research efforts driven by the need for better drug carries and biomedical devices. In contrast to these advancements, fabrication of shape-memory particles which actuate at body temperature remains scarce. We developed a shape-memory microparticle system with dynamically tunable shapes under physiological temperature. Temperature-responsive poly(ε-caprolactone) (PCL) microparticles were successfully prepared by an in situ oil-in-water (o/w) emulsion polymerization technique using linear telechelic and tetra-branched PCL macromonomers. By optimizing the mixing ratios of branched PCL macromonomers, the crystal-amorphous transition temperature was adjusted to the biological relevant temperature. The particles with a disk-like temporal shape were achieved by compression. The shape recovery from the disk to spherical shape was also realized at 37 °C. We also incorporated magnetic nanoparticles within the PCL microparticles, which can be remote-controllable by a magnet, in such a way that they can be actuated and manipulated in a controlled way.

ACS Style

Koichiro Uto; Mitsuhiro Ebara. Magnetic-Responsive Microparticles that Switch Shape at 37 °C. Applied Sciences 2017, 7, 1203 .

AMA Style

Koichiro Uto, Mitsuhiro Ebara. Magnetic-Responsive Microparticles that Switch Shape at 37 °C. Applied Sciences. 2017; 7 (11):1203.

Chicago/Turabian Style

Koichiro Uto; Mitsuhiro Ebara. 2017. "Magnetic-Responsive Microparticles that Switch Shape at 37 °C." Applied Sciences 7, no. 11: 1203.