Koichiro Uto - Academia.edu (original) (raw)
Papers by Koichiro Uto
International Journal of Biological Macromolecules
Biomaterials Science
This paper proposes a shape-memory balloon (SMB) to improve bone cement injection efficiency and ... more This paper proposes a shape-memory balloon (SMB) to improve bone cement injection efficiency and postoperative thermo/chemotherapy for bone tumors.
International Journal of Molecular Sciences
This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can ... more 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.
Polymers
Vital pulp therapy is an important endodontic treatment. Strategies using growth factors and biol... more 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 reveale...
Biomaterials Science
Temporal elasticity and roughness modulation with temperature-responsive poly(ε-caprolactone) ind... more Temporal elasticity and roughness modulation with temperature-responsive poly(ε-caprolactone) induced the alternation of hepatocellular function dynamically.
International Journal of Molecular Sciences
Background: We propose the potential studies on material fluidity to induce epithelial to mesench... more 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...
Plastic and Reconstructive Surgery - Global Open
Cold Spring Harbor Perspectives in Biology
Applied Sciences
Shape-memory polymers have seen tremendous research efforts driven by the need for better drug ca... more 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.
Advanced Healthcare Materials
Fibers
Excellent water-absorbing nanofiber meshes were developed as a potential material for removing ex... more 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...
This paper reports a rational design of temperature-responsive nanofiber meshes with shape-memory... more This paper reports a rational design of temperature-responsive nanofiber meshes with shape-memory effect. The meshes were fabricated by electrospinning a poly(ε-caprolactone) (PCL)-based polyurethane with different contents of soft and hard segments. The effects of PCL diol/hexamethylene diisocyanate (HDI)/1,4-butanediol (BD) molar ratio in terms of the contents of soft and hard segments on the shape-memory properties were investigated. Although the mechanical property improved with increasing hard segment ratio, optimal shape-memory properties were obtained with a PCL/HDI/BD molar ratio of 1:4:3. At a microscopic level, the original nanofibrous structure was easily deformed into a temporary shape, and recovered its original structure when the sample was reheated. A higher recovery rate (>89%) was achieved even when the mesh was deformed up to 400%. Finally, the nanofiber meshes were used to control the alignment of human mesenchymal stem cells (hMSCs). The hMSCs aligned ...
Theranostics, 2017
Objective: We propose here material-induced senescence (MIS) as a new therapeutic concept that li... more Objective: We propose here material-induced senescence (MIS) as a new therapeutic concept that limits cancer progression by stable cell cycle arrest. This study examined for the first time the effect of material fluidity on cellular senescence in lung carcinoma using poly(ε-caprolactone-co-D, L-lactide) (P(CL-co-DLLA)) with tunable elasticity and fluidity. Methods: The fluidity was varied by chemically crosslinking the polymer networks: the crosslinked P(CL-co-DLLA) shows solid-like properties with a stiffness of 260 kPa, while the non-crosslinked polymer exists in a quasi-liquid state with loss and storage moduli of 33 kPa and 11 kPa, respectively. Results: We found that cancer cells growing on the non-crosslinked, fluidic substrate undergo a non-apoptotic form of cell death and the cell cycle was accumulated in a G0/G1 phase. Next, we investigated the expression of biomarkers that are associated with cancer pathways. The cancer cells on the fluidic substrate expressed several biom...
Advanced healthcare materials, 2017
A novel shape-memory cell culture platform has been designed that is capable of simultaneously tu... more A novel shape-memory cell culture platform has been designed that is capable of simultaneously tuning surface topography and dimensionality to manipulate cell alignment. By crosslinking poly(ε-caprolactone) (PCL) macromonomers of precisely designed nanoarchitectures, a shape-memory PCL with switching temperature near body temperature is successfully prepared. The temporary strain-fixed PCLs are prepared by processing through heating, stretching, and cooling about the switching temperature. Temporary nanowrinkles are also formed spontaneously during the strain-fixing process with magnitudes that are dependent on the applied strain. The surface features completely transform from wrinkled to smooth upon shape-memory activation over a narrow temperature range. Shape-memory activation also triggers dimensional deformation in an initial fixed strain-dependent manner. A dynamic cell-orienting study demonstrates that surface topographical changes play a dominant role in cell alignment for s...
Acta biomaterialia, Apr 5, 2017
Peripheral nerve injury is one of common traumas. Although injured peripheral nerves have the cap... more Peripheral nerve injury is one of common traumas. Although injured peripheral nerves have the capacity to regenerate, axon regeneration proceeds slowly and functional outcomes are often poor. Pharmacological enhancement of regeneration can play an important role in increasing functional recovery. In this study, we developed a novel electrospun nanofiber sheet incorporating methylcobalamin (MeCbl), one of the active forms of vitamin B12 homologues, to deliver it enough locally to the peripheral nerve injury site. We evaluated whether local administration of MeCbl at the nerve injury site was effective in promoting nerve regeneration. Electrospun nanofiber sheets gradually released MeCbl for at least 8weeks when tested in vitro. There was no adverse effect of nanofiber sheets on function in vivo of the peripheral nervous system. Local implantation of nanofiber sheets incorporating MeCbl contributed to the recovery of the motor and sensory function, the recovery of nerve conduction vel...
Materials, 2015
Inactivated Hemagglutinating Virus of Japan Envelope (HVJ-E) was immobilized on electrospun nanof... more Inactivated Hemagglutinating Virus of Japan Envelope (HVJ-E) was immobilized on electrospun nanofibers of poly(ε-caprolactone) by layer-by-layer (LbL) assembly technique. The precursor LbL film was first constructed with poly-L-lysine and alginic acid via electrostatic interaction. Then the HVJ-E particles were immobilized on the cationic PLL outermost surface. The HVJ-E adsorption was confirmed by surface wettability test, scanning laser microscopy, scanning electron microscopy, and confocal laser microscopy. The immobilized HVJ-E particles were released from the nanofibers under physiological condition. In vitro cytotoxic assay demonstrated that the released HVJ-E from nanofibers induced cancer cell deaths. This surface immobilization technique is possible to perform on anti-cancer drug incorporated nanofibers that enables the fibers to show chemotherapy and immunotherapy simultaneously for an effective eradication of tumor cells in vivo.
International Journal of Biological Macromolecules
Biomaterials Science
This paper proposes a shape-memory balloon (SMB) to improve bone cement injection efficiency and ... more This paper proposes a shape-memory balloon (SMB) to improve bone cement injection efficiency and postoperative thermo/chemotherapy for bone tumors.
International Journal of Molecular Sciences
This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can ... more 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.
Polymers
Vital pulp therapy is an important endodontic treatment. Strategies using growth factors and biol... more 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 reveale...
Biomaterials Science
Temporal elasticity and roughness modulation with temperature-responsive poly(ε-caprolactone) ind... more Temporal elasticity and roughness modulation with temperature-responsive poly(ε-caprolactone) induced the alternation of hepatocellular function dynamically.
International Journal of Molecular Sciences
Background: We propose the potential studies on material fluidity to induce epithelial to mesench... more 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...
Plastic and Reconstructive Surgery - Global Open
Cold Spring Harbor Perspectives in Biology
Applied Sciences
Shape-memory polymers have seen tremendous research efforts driven by the need for better drug ca... more 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.
Advanced Healthcare Materials
Fibers
Excellent water-absorbing nanofiber meshes were developed as a potential material for removing ex... more 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...
This paper reports a rational design of temperature-responsive nanofiber meshes with shape-memory... more This paper reports a rational design of temperature-responsive nanofiber meshes with shape-memory effect. The meshes were fabricated by electrospinning a poly(ε-caprolactone) (PCL)-based polyurethane with different contents of soft and hard segments. The effects of PCL diol/hexamethylene diisocyanate (HDI)/1,4-butanediol (BD) molar ratio in terms of the contents of soft and hard segments on the shape-memory properties were investigated. Although the mechanical property improved with increasing hard segment ratio, optimal shape-memory properties were obtained with a PCL/HDI/BD molar ratio of 1:4:3. At a microscopic level, the original nanofibrous structure was easily deformed into a temporary shape, and recovered its original structure when the sample was reheated. A higher recovery rate (>89%) was achieved even when the mesh was deformed up to 400%. Finally, the nanofiber meshes were used to control the alignment of human mesenchymal stem cells (hMSCs). The hMSCs aligned ...
Theranostics, 2017
Objective: We propose here material-induced senescence (MIS) as a new therapeutic concept that li... more Objective: We propose here material-induced senescence (MIS) as a new therapeutic concept that limits cancer progression by stable cell cycle arrest. This study examined for the first time the effect of material fluidity on cellular senescence in lung carcinoma using poly(ε-caprolactone-co-D, L-lactide) (P(CL-co-DLLA)) with tunable elasticity and fluidity. Methods: The fluidity was varied by chemically crosslinking the polymer networks: the crosslinked P(CL-co-DLLA) shows solid-like properties with a stiffness of 260 kPa, while the non-crosslinked polymer exists in a quasi-liquid state with loss and storage moduli of 33 kPa and 11 kPa, respectively. Results: We found that cancer cells growing on the non-crosslinked, fluidic substrate undergo a non-apoptotic form of cell death and the cell cycle was accumulated in a G0/G1 phase. Next, we investigated the expression of biomarkers that are associated with cancer pathways. The cancer cells on the fluidic substrate expressed several biom...
Advanced healthcare materials, 2017
A novel shape-memory cell culture platform has been designed that is capable of simultaneously tu... more A novel shape-memory cell culture platform has been designed that is capable of simultaneously tuning surface topography and dimensionality to manipulate cell alignment. By crosslinking poly(ε-caprolactone) (PCL) macromonomers of precisely designed nanoarchitectures, a shape-memory PCL with switching temperature near body temperature is successfully prepared. The temporary strain-fixed PCLs are prepared by processing through heating, stretching, and cooling about the switching temperature. Temporary nanowrinkles are also formed spontaneously during the strain-fixing process with magnitudes that are dependent on the applied strain. The surface features completely transform from wrinkled to smooth upon shape-memory activation over a narrow temperature range. Shape-memory activation also triggers dimensional deformation in an initial fixed strain-dependent manner. A dynamic cell-orienting study demonstrates that surface topographical changes play a dominant role in cell alignment for s...
Acta biomaterialia, Apr 5, 2017
Peripheral nerve injury is one of common traumas. Although injured peripheral nerves have the cap... more Peripheral nerve injury is one of common traumas. Although injured peripheral nerves have the capacity to regenerate, axon regeneration proceeds slowly and functional outcomes are often poor. Pharmacological enhancement of regeneration can play an important role in increasing functional recovery. In this study, we developed a novel electrospun nanofiber sheet incorporating methylcobalamin (MeCbl), one of the active forms of vitamin B12 homologues, to deliver it enough locally to the peripheral nerve injury site. We evaluated whether local administration of MeCbl at the nerve injury site was effective in promoting nerve regeneration. Electrospun nanofiber sheets gradually released MeCbl for at least 8weeks when tested in vitro. There was no adverse effect of nanofiber sheets on function in vivo of the peripheral nervous system. Local implantation of nanofiber sheets incorporating MeCbl contributed to the recovery of the motor and sensory function, the recovery of nerve conduction vel...
Materials, 2015
Inactivated Hemagglutinating Virus of Japan Envelope (HVJ-E) was immobilized on electrospun nanof... more Inactivated Hemagglutinating Virus of Japan Envelope (HVJ-E) was immobilized on electrospun nanofibers of poly(ε-caprolactone) by layer-by-layer (LbL) assembly technique. The precursor LbL film was first constructed with poly-L-lysine and alginic acid via electrostatic interaction. Then the HVJ-E particles were immobilized on the cationic PLL outermost surface. The HVJ-E adsorption was confirmed by surface wettability test, scanning laser microscopy, scanning electron microscopy, and confocal laser microscopy. The immobilized HVJ-E particles were released from the nanofibers under physiological condition. In vitro cytotoxic assay demonstrated that the released HVJ-E from nanofibers induced cancer cell deaths. This surface immobilization technique is possible to perform on anti-cancer drug incorporated nanofibers that enables the fibers to show chemotherapy and immunotherapy simultaneously for an effective eradication of tumor cells in vivo.