Nobutaka Hanagata

Tokyo Institute of Technology, Edo, Tōkyō, Japan

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Publications (134)472.04 Total impact

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    ABSTRACT: The interaction of antimetabolite 5-fluorouracil (5FU) with bovine serum albumin (BSA) under UVC (253.7 nm) irradiation was investigated in the present study using UV-Vis spectroscopy, steady state/time resolved fluorescence spectroscopic techniques. The stability of protein was found to be very strong when BSA gets bind to 5FU and moreover it is compared with the free BSA under UVC irradiation. From the fluorescence spectroscopic study, the stability of the complex was found to acquire 2-fold stronger than free protein. From the molecular modelling studies, we came to know the hydrogen bonds between BSA and antimetabolite 5FU are strong, up to 70.4 J/m 2 under UVC irradiation.
    International Journal of Spectroscopy 01/2015; 2015:1-12.
  • Cuilian Tao, Yufang Zhu, Xianglan Li, Nobutaka Hanagata
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    ABSTRACT: We developed a potential cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) delivery system by binding of CpG ODN onto aminated mesoporous silica nanoparticles (MSNs) to form CpG/MSN-NH2 complexes for Toll-like receptor 9 (TLR9)-mediated induction of cytokines. Serum stability, in vitro cytotoxicity, cellular uptake, and interleukin-6 (IL-6) induction of CpG/MSN-NH2 complexes were investigated. The results showed that MSN-NH2 nanoparticles had no cytotoxicity to Raw 264.7 cells, and binding of CpG ODN to MSN-NH2 nanoparticles enhanced serum stability of CpG ODN due to the protection by nanoparticles. Furthermore, CpG/MSN-NH2 complexes could be efficiently taken up by cells due to small particle size and good dispersity. Most importantly, CpG/MSN-NH2 complexes significantly enhanced the level of IL-6 induction, stimulated by interaction between CpG ODN and TLR9 in endolysosomes. Therefore, MSNs would be a promising carrier for enhancing the delivery efficiency of CpG ODN.
    Microporous and Mesoporous Materials 11/2014; · 3.21 Impact Factor
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    ABSTRACT: Theranostic nanoparticles currently have been regarded as an emerging concept of 'personalized medicine' with diagnostic and therapeutic dual-functions. Eu3+ doped hydroxyapatite (HAp) has been regarded as a promising fluorescent probe for in vivo imaging applications. Additionally, substitution of Ca2+ with Fe3+ in HAp crystal may endow the capability of producing heat upon exposure to a magnetic field. Here we report a preliminary study of doping mechanism and photoluminescence of Eu3+ and Fe3+ doped HAp nanoparticles (Eu/Fe:HAp). HAp with varied concentration of Eu3+ and Fe3+ doping are presented as Eu(10 mol%):HAp, Eu(7 mol%)-Fe(3 mol%):HAp, Eu(5 mol%)-Fe(5 mol%):HAp, Eu(3 mol%)-Fe(7 mol%):HAp, and Fe(10 mol%):HAp in the study. The results showed that the HAp particles, in nano-size with rod-like morphology, were successfully doped with Eu3+ and Fe3+, and the particles can be well suspended in cell culture medium. Photoluminescence analysis revealed that particles have prominent emissions at 536 nm, 590 nm, 615 nm, 650 nm and 695 nm upon excitation at a wavelength of 397 nm. Moreover, these Eu/Fe:HAp nanoparticles belonged to B-type carbonated HAp, which has been considered an effective biodegradable and biocompatible drug/gene carrier in biological applications.
    Science and Technology of Advanced Materials 09/2014; 15(5):055005. · 2.61 Impact Factor
  • Cuilian Tao, Yufang Zhu, Xianglan Li, Nobutaka Hanagata
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    ABSTRACT: We developed a potential cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) delivery system based on magnetic mesoporous silica (MMS) nanoparticles by binding of CpG ODN onto aminated MMS (MMS-NH2) nanoparticles to form CpG/MMS-NH2 complexes for Toll-like receptor 9 (TLR9)-mediated induction of cytokines. Magnetization, serum stability, in vitro cytotoxicity, cellular uptake, and interleukin-6 (IL-6) induction of CpG/MMS-NH2 complexes were evaluated. The results showed that MMS nanoparticles exhibited superparamagnetic behavior with a saturation magnetization of 6.5 emu/g. Also, MMS-NH2 nanoparticles had no cytotoxicity to Raw 264.7 cells, and CpG/MMS-NH2 complexes enhanced serum stability of CpG ODN and could be localized in the endolysosomes after endocytosis by cells. Importantly, CpG/MMS-NH2 complexes significantly enhanced the TLR9-mediated IL-6 induction compared to free CpG ODN. Therefore, CpG/MMS-NH2 complexes could be magnetic targeted delivery and significantly enhance the TLR9-mediated cytokine induction for stimulating immune responses.
    RSC Advances 09/2014; · 3.71 Impact Factor
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    ABSTRACT: T cell receptor (TCR) phosphorylation requires the kinase Lck and the phosphatase CD45. CD45 activates Lck by dephosphorylating an inhibitory tyrosine of Lck to relieve autoinhibition. However, CD45 also dephosphorylates the TCR, and the spatial exclusion of CD45 from TCR clustering in the plasma membrane appears to attenuate this negative effect of CD45. To further investigate the role of CD45 in signal initiation, we reconstituted membrane TCR clusters in vitro on supported lipid bilayers. Fluorescence microscopy of single clusters showed that incorporation of CD45 enhanced phosphorylation of TCR clusters, but only when Lck co-clustered with TCR. We found that clustered Lck autophosphorylated the inhibitory tyrosine and thus could be activated by CD45, whereas diffusive Lck molecules did not. In the TCR-Lck clusters and at low CD45 density, we speculate that the effect of Lck activation may overcome dephosphorylation of TCR, resulting in a net positive regulation. The CD45 density in physiological TCR clusters is also low owing to the exclusion of CD45. Thus, we propose that the spatial organization of TCR/Lck/CD45 in T cell membranes is important not only for modulating the negative role of CD45 but also for creating conditions in which CD45 has a positive role in signal initiation.
    Journal of Biological Chemistry 08/2014; · 4.60 Impact Factor
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    ABSTRACT: To evaluate the in vivo foreign body reaction to bio-inert 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers, MPC polymer-coated porous substrates, with large surface area, were implanted subcutaneously in mice for 7 and 28 days, and the surrounding tissue response and cells infiltrating into the porous structure were evaluated. The MPC polymer surface induced low angiogenesis and thin encapsulation around the porous substrate, and slightly suppressed cell infiltration into the porous substrate. M1-type macrophage specific gene (CCR7) expression was suppressed by the MPC polymer surface after 7 days, resulting in the suppression of inflammatory cytokine/chemokine gene expression. However, the expression of these genes on the MPC polymer surface was higher than on the non-coated surface after 28 days. These findings suggest that MPC polymer surfaces successfully inhibit inflammatory responses during the early stage of tissue response, and seem to retard its occurrence over time.
    Journal of Biomaterials Science Polymer Edition 07/2014; · 1.36 Impact Factor
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    ABSTRACT: Graphene-like two-dimensional materials (2DMats) show application potential in optoelectronics and biomedicine due to their unique properties. However, environmental and biological influences of these 2DMats remain to be unveiled. Here we reported the antibacterial activity of two-dimensional (2D) chemically exfoliated MoS2 (ce-MoS2) sheets. We found that the antibacterial activity of ce-MoS2 sheets was much more potent than that of the raw MoS2 powders used for the synthesis of ce-MoS2 sheets possibly due to the 2D planar structure (high specific surface area) and higher conductivity of the ce-MoS2. We investigated the antibacterial mechanisms of the ce-MoS2 sheets and proposed their antibacterial pathways. We found that the ce-MoS2 sheets could produce reactive oxygen species (ROS), different from a previous report on graphene-based materials. Particularly, the oxidation capacity of the ce-MoS2 sheets toward glutathione oxidation showed a time and concentration dependent trend, which is fully consistent with the antibacterial behaviour of the ce-MoS2 sheets. The results suggest that antimicrobial behaviors were attributable to both membrane and oxidation stress. The antibacterial pathways include MoS2-bacteria contact induced membrane stress, superoxide anion (O2˙(-)) induced ROS production by the ce-MoS2, and the ensuing superoxide anion-independent oxidation. Our study thus indicates that the tailoring of the dimension of nanomaterials and their electronic properties would manipulate antibacterial activity.
    Nanoscale 07/2014; · 6.74 Impact Factor
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    ABSTRACT: Novel silica hollow flowers (1–5 μm) were synthesized using globular apatite flowers as sacrificed template via a sol–gel route and then employed as biocompatible carrier of bone morphogenetic protein-2 (BMP-2) to stimulate osteoblast differentiation. Apatite was bio-mimetically synthesized from a well-known Kokubo’s simulated body fluid (SBF), then coated with silica in a Stöber-type silica sol–gel system, and finally dissolved in an acetic solution to yield silica hollow flowers. Analyses of SEM and TEM images show that the resultant silica flowers had a porous and hollow structure due to removal of apatite template by acetic treatment and their shell was constructed by numerous silica nanosheets (∼10 nm in silica shell). A larger specific surface of 890 m2/g was obtained for silica hollow flowers compared to silica-coated apatite due to the presence of porous and hollow structure. Silica hollow flowers had no significant toxicity after incubation with osteoblast MC3T3-E1 cells, indicating a good biocompatibility. They favored adsorption and supported a sustained release behavior of BMP-2. The released BMP-2 was biological active and enhanced osteoblast differentiation with higher ALP activity and larger amount of osteocalcin. The present silica hollow flowers are thus applicable to delivery system in tissue generation.
    Chemical Engineering Journal 06/2014; 246:1–9. · 4.06 Impact Factor
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    ABSTRACT: Developing materials for "Nano-vehicles" with clinically approved drugs encapsulated is envisaged to enhance drug therapeutic effects and reduce the adverse effects. However, design and preparation of the biomaterials that are porous, nontoxic, soluble and stable in physiological solutions, and could be easily functionalized for effective drug deliveries are still challenging. Here we report an original and simple thermal substitution method to fabricate perfectly water-soluble and porous boron nitride (BN) materials featuring unprecedentedly high hydroxylation degrees. These hydroxylated BNs are biocompatible and can effectively load anticancer drugs (e.g. doxorubicin, DOX) up to contents three times exceeding their own weight. The same or even fewer drugs that are loaded on such BN carriers exhibit much higher potency for reducing the viability of LNcaP cancer cells than free drugs.
    ACS Nano 05/2014; · 12.03 Impact Factor
  • Kota Shiba, Motohiro Tagaya, Nobutaka Hanagata
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    ABSTRACT: Luminescent titania-fluorescein (FS) hybrid nanoparticles (NPs) were successfully synthesized by a sol–gel reaction of titanium alkoxide in the presence of octadecylamine using a fluidic reactor with a Y-type channel. The molar ratio of FS/Ti ratio was varied in the range from 1/1000 to 1/100 in order to obtain the hybrid NPs with the different luminescent behavior. The shape of the NPs is spherical and their sizes are 400 nm which is almost the same irrespective of the FS content, suggesting the different FS molecular states in one NP. We also demonstrated that the hybrid NPs exhibited a characteristic luminescence; the NPs with the higher and lower FS contents exhibited an enhanced luminescence in PBS and air, respectively, indicating that the FS states responded to the molecular environment. Through cytocompatible experiments using the NPs, it turned out that they had a high compatibility for fibroblasts. Therefore, the preparation of a series of the luminescent NPs with a tunable luminescence property was achieved. The results will lead to a guideline to determine a proper combination between material composition and an environment where they are used, being useful for biomedical applications.
    ACS Applied Materials & Interfaces 04/2014; 6(9):6825–6834. · 5.90 Impact Factor
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    ABSTRACT: Chitosan/cytosine-phosphodiester-guanine oligodeoxynucleotide (CpG ODN) nanoparticles as potential immunostimulatory adjuvants were synthesized by the conventional bulk mixing (BM) method and a novel microfluidic (MF) method. Their size and size distribution, CpG ODN loading efficiency, surface charge, biocompatibility, cellular uptake, and immunostimulatory response were investigated. In the BM method, nanoparticles were synthesized by vortexing a mixture of chitosan solution and CpG ODN2006x3-PD solution. In the MF method, the nanoparticles were synthesized by rapidly mixing a chitosan solution and CpG ODN solution in a poly(dimethylsiloxane) microfluidic device. Our results indicated that particle size and size distribution, CpG ODN loading efficiency, and surface charge could be easily adjusted by using the tuning preparation method and controlling the flow ratio of fluid rates in the different microfluidic channels. Compared with the BM method, the MF method yielded a decrease in particle size and size range, an increase in CpG ODN loading efficiency, and a decrease in surface charge. After the particles were exposed to 293XL-hTLR9 cells, a water-soluble tetrazolium salt assay indicated that the BM and MF-processed nanoparticles had no significant toxicity and were biocompatible. An immunochemical assay indicated that both types of nanoparticles entered 293XL-hTLR9 cells and were located in the endolysosomes. The MF-processed nanoparticles showed much higher cellular uptake efficiency. After the particles were exposed to peripheral blood mononuclear cells, an enzyme-linked immunosorbent assay quantitatively indicated that both types of nanoparticles stimulated the production of interleukin-6 and the MF-processed nanoparticles showed a much stronger immunostimulatory response. These results indicate that the MF method can be used to synthesize nanoparticles with a controllable size and size range for enhancing the biological activity of DNA and other biomolecules.
    Lab on a Chip 04/2014; · 5.70 Impact Factor
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    ABSTRACT: Boron nitride nanotubes@NaGdF4:Eu composites with core@shell structures were fabricated giving the opportunity to trace, target and thus to manipulate BNNTs in vitro. The composites show a significantly higher cellular uptake and chemotherapy drug intracellular delivery ability in the presence of an external magnetic field than that in its absence.
    Chemical Communications 03/2014; · 6.38 Impact Factor
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    ABSTRACT: a b s t r a c t 5-Fluorouracil is clinically used as antitumor drug to treat many types of cancer, which is made available to the target tissues in conjugation with transport protein serum albumin. 5-Fluorouracil which is low toxic when compared to the other drugs of this family and hence its binding characteristics are therefore of prime interest. The steady state and time resolved fluorescence studies, Fourier transform infrared spectroscopy and circular dichroism studies were employed to explain the mode and the mechanism of interaction of 5FU with BSA. 5-Fluorouracil binding is characterized with one high affinity binding site, with the binding constant of the order of 10 4 . The molecular distance r ($1.5 nm) between donor (bovine serum abumin) and acceptor (5-fluorouracil) was estimated according to Forster's theory of non-radiative energy transfer. The feature of 5-fluorouracil induced structural changes of bovine serum albumin has been studied in detail by circular dichroism and Fourier transform infrared spectroscopy analysis. The binding dynamics was expounded by synchronous fluorescence spectroscopy, florescence lifetime measurements and molecular modeling elicits that hydrophobic interactions and hydrogen bonding, stabilizes the 5-fluorouracil interaction with BSA. & 2014 Elsevier B.V. All rights reserved.
    Journal of Luminescence 02/2014; 151:1-10. · 2.37 Impact Factor
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    ABSTRACT: We developed a potential immunostimulatory double-stranded DNA (dsDNA) delivery system by the binding of dsDNA to amino-modified mesoporous silica nanoparticles (MSNs) to form MSN-NH2/dsDNA complexes. Serum stability, in vitro cytotoxicity, cell uptake, and type I interferon-α (IFN-α) induction of MSN-NH2/dsDNA complexes were evaluated. The results showed that MSN-NH2 nanoparticles had no cytotoxicity to Raw 264.7 cells, and MSN-NH2/dsDNA complexes enhanced the serum stability of dsDNA due to the protection by nanoparticles and exhibited a high efficiency of cell uptake due to a small particle size and excellent dispersity. Most importantly, MSN-NH2/dsDNA complexes significantly enhanced the level of IFN-α induction, triggered by cytosolic DNA sensor proteins. Therefore, binding of immunostimulatory DNA to MSNs would play a promising role for enhancing the delivery efficiency of immunostimulatory DNA drugs.
    Dalton Transactions 02/2014; · 4.10 Impact Factor
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    ABSTRACT: To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of early host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1β and IL-10 are important cytokines in tissue responses to biomaterials because IL-1β promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1β was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1- and M2-macrophage-related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these genetic regulations.
    PLoS ONE 01/2014; 9(1):e85132. · 3.53 Impact Factor
    This article is viewable in ResearchGate's enriched format
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    ABSTRACT: An environmental cell with a 50-nm-thick cathodolumi-nescent window was attached to a scanning electron microscope, and diffraction-unlimited near-field optical imaging of unstained living human lung epithelial cells in liquid was demonstrated. Electrons with energies as low as 0.8 – 1.2 kV are sufficiently blocked by the window without damaging the specimens, and form a sub-wavelength-sized illumination light source. A super-resolved optical image of the specimen adhered to the opposite window surface was acquired by a photomultiplier tube placed below. The cells after the observation were proved to stay alive. The image was formed by enhanced dipole radiation or energy transfer, and features as small as 62 nm were resolved.
    Optics Express 11/2013; 21(23):28198-28218. · 3.53 Impact Factor
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    ABSTRACT: We have prepared multifunctional magnetic mesoporous Fe-CaSiO3 materials using triblock copolymer (P123) as a structure-directing agent. The effects of Fe substitution on the mesoporous structure, in vitro bioactivity, magnetic heating ability and drug delivery property of mesoporous CaSiO3 materials were investigated. Mesoporous Fe-CaSiO3 materials had similar mesoporous channels (5-6 nm) with different Fe substitution. When 5 and 10% Fe were substituted for Ca in mesoporous CaSiO3 materials, mesoporous Fe-CaSiO3 materials still showed good apatite-formation ability and had no cytotoxic effect on osteoblast-like MC3T3-E1 cells evaluated by the elution cell culture assay. On the other hand, mesoporous Fe-CaSiO3 materials could generate heat to raise the temperature of the surrounding environment in an alternating magnetic field due to their superparamagnetic property. When we use gentamicin (GS) as a model drug, mesoporous Fe-CaSiO3 materials release GS in a sustained manner. Therefore, magnetic mesoporous Fe-CaSiO3 materials would be a promising multifunctional platform with bone regeneration, local drug delivery and magnetic hyperthermia.
    Science and Technology of Advanced Materials 10/2013; 14(5):5009-. · 3.75 Impact Factor
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    ABSTRACT: Recently, one of the interferon-induced transmembrane (IFITM) family proteins, IFITM3, has become an important target for the activity against influenza A (H1N1) virus infection. In this protein, a post-translational modification by fatty acids covalently attached to cysteine, termed S-palmitoylation, plays a crucial role for the antiviral activity. IFITM3 possesses three cysteine residues for the S-palmitoylation in the first transmembrane (TM1) domain and in the cytoplasmic (CP) loop. Because these cysteines are well conserved in the mammalian IFITM family proteins, the S-palmitoylation on these cysteines is significant for their functions. IFITM5 is another IFITM family protein and interacts with the FK506-binding protein 11 (FKBP11) to form a higher-order complex in osteoblast cells, which induces the expression of immunologically relevant genes. In this study, we investigated the role played by S-palmitoylation of IFITM5 in its interaction with FKBP11 in the cells, because this interaction is a key process for the gene expression. Our investigations using an established reporter, 17-octadecynoic acid (17-ODYA), and an inhibitor for the S-palmitoylation, 2-bromopalmitic acid (2BP), revealed that IFITM5 was S-palmitoylated in addition to IFITM3. Specifically, we found that cysteine residues in the TM1 domain and in the CP loop were S-palmitoylated in IFITM5. Then, we revealed by immunoprecipitation and western blot analyses that the interaction of IFITM5 with FKBP11 was inhibited in the presence of 2BP. The mutant lacking the S-palmitoylation site in the TM1 domain lost the interaction with FKBP11. These results indicate that the S-palmitoylation on IFITM5 promotes the interaction with FKBP11. Finally, we investigated bone nodule formation in osteoblast cells in the presence of 2BP, because IFITM5 was originally identified as a bone formation factor. The experiment resulted in a morphological aberration of the bone nodule. This also indicated that the S-palmitoylation contributes to bone formation.
    PLoS ONE 09/2013; 8(9):e75831. · 3.53 Impact Factor
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    ABSTRACT: Semiconductor nanoparticles (or quantum dots, QDs) exhibit unique optical and electronic properties such as size-controlled fl uorescence, high quantum yields, and stability against photobleaching. These properties allow QDs to be used as optical labels for multiplexed imaging and in drug delivery detection systems. Luminescent silicon QDs and surface-modifi ed silicon QDs have also been developed as potential minimally toxic fl uorescent probes for bioapplications. Silicon, a well-known power electronic semiconductor material, is considered an extremely biocompatible material, in particular with respect to blood. This review article summarizes existing knowledge related to and recent research progress made in the methods for synthesizing silicon QDs, as well as their optical properties and surface-modifi cation processes. In addition, drug delivery systems and in vitro and in vivo imaging applications that use silicon QDs are also discussed.
    Advanced Healthcare Materials 08/2013;
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    ABSTRACT: Since the discovery of carbon nanotubes by Iijima et al., [ 1 ] carbon nanotubes and inorganic nanotubes have become very important in electronic, photothermal, and biomedical applica-tions because of their unique one-dimensional tubular struc-tures, high surface-to-volume ratios, and excellent mechanical properties and biocompatibilities. [ 2–5 ] Inorganic nanotubes have been micropatterned with highly organized spatial microstruc-tures for the realization of physicochemical and biomedical properties that are superior to those of the individual nano-tubes. Miyako et al. micropatterned sodium dodecyl sulfate (SDS) carbon-nanotube agarose gel to create photothermal materials, [ 2 ] and Park et al. micropatterned carbon nanotube monolayers on Au fi lms coated on glass slides in order to direct the growth of mesenchymal stem cells. [ 3 ] In addition, Zhang et al. micropatterned carbon nanotubes on silicon substrates to guide neurite growth, [ 4 ] while Pittrof et al. micropatterned TiO 2 nanotubes on Ti foils for the site-selective nucleation of bone-like apatite, which stimulated bone generation. [ 5 ] However, in most cases, the micropatterning procedure not only involved multiple complex steps, but also generally needed a supporting substrate, seriously limiting the practical applications of these micropatterned samples. Therefore, the fabrication of free-standing, micropatterned inorganic nanotubes is still a signifi -cant challenge. In the present study, we developed the facile and large-scale fabrication of free-standing, micropatterned silica nanotubes via a hybrid hydrogel-based template route. Silica nanotubes are typical inorganic nanotubes, and have been explored as die-lectric materials for nanoelectronics applications, [ 6 ] as carriers for anti-cancer drugs and DNA, and as biocompatible matrices for enzymes. [ 7–9 ] Compared with other kinds of nanotubes such as carbon and titania nanotubes, silica nanotubes are not only more easily fabricated via an ambient and low-cost sol-gel route, but also exhibit better biocompatibility because of their hydrophilic silanol groups (Si–OH) and silicate networks (Si– O–Si). [ 10 ] Thus, micropatterned silica nanotubes may be inter-esting and useful for practical applications. Figure 1 (a) illustrates the fabrication procedure for the large-scale production of free-standing, micropatterned silica nano-tubes. Collagen fi bril hydrogels (named Co) were reassembled in vitro in a silicone rubber mold (1 cm × 1 cm × 0.2 cm) by neutralizing 0.5% (w/v) acid-soluble type-I collagen with phosphate buffered saline (PBS, 1370 mM NaCl, 27 mM KCl, 80 mM Na 2 HPO 4 , and 15 mM KH 2 PO 4) in a collagen/PBS volume ratio of 9/1 at 37 ° C for 2 h. They were then soaked in a conventional Stöber-type sol-gel system consisting of tetraethy-lorthosilicate (TEOS, 1 mL), ethanol (9 mL), water (9 mL), and ammonia (28%, 0.5 mL) at room temperature for 12 h to yield a silica-coated collagen fi bril hybrid hydrogel (named SiCo). Sub-sequently, the SiCo was placed on either a fl at polydimethylsi-loxane (PDMS) sheet or a microgrooved PDMS mold (200 μ m in ridge width, 180 μ m in groove width, and 50 μ m in depth, 1 cm × 1 cm), which was maintained at 50 ° C in an incubator. At the same time, a force (5 N) was applied to the SiCo sur-face. After 12 h, the SiCo was compressed and dried to produce silica-coated collagen fi bril hybrid membranes with either a fl at surface (named FSiCo) or a microgrooved surface (named MGSiCo). Finally, both FSiCo and MGSiCo were calcined at 600 ° C for 2 h to remove the collagen fi brils and produce the corresponding silica nanotube membrane with either a fl at sur-face (named FSi) or a microgrooved surface (named MGSi). Figure 1 (b) shows the photographs of Co, SiCo, MGSiCo, and MGSi. Scanning electron microscopy images of FSiCo (a, b), MGSiCo (c, d), and MGSi (e) are shown in Figure 2 . When SiCo was compressed and dried on the fl at PDMS sheet, the resultant FSiCo (Figure 2 (a)) exhibited a similar fl at and smooth surface with a porous and fi brous structure (Figure 2 (b)) owing to the presence of the collagen fi brils. When SiCo was compressed and dried on the microgrooved PDMS mold, the resultant MGSiCo (Figure 2 (c)) exhibited a typical microgroove/ridge surface topography (about 200 μ m in groove width and about 180 μ m in ridge width). The high-magnifi cation image in Figure 2 (d) clearly shows that both the ridge and microgroove parts were fi brous, indicating that the silica-coated collagen fi bril hybrid hydrogel could be micropatterned well. After calcination, the
    Advanced Healthcare Materials. 08/2013; 2:1091-1095.

Publication Stats

2k Citations
472.04 Total Impact Points


  • 2011–2014
    • Tokyo Institute of Technology
      • Department of Metallurgy and Ceramics Science
      Edo, Tōkyō, Japan
    • Zhejiang University
      • State Key Lab of Silicon Materials
      Hangzhou, Zhejiang Sheng, China
  • 2006–2014
    • National Institute for Materials Science
      • • Nanotechnology Innovation Station
      • • International Center for Young Scientist (ICYS)
      Tsukuba, Ibaraki, Japan
  • 2013
    • National Institutes for Food and Drug Control, China
      Peping, Beijing, China
  • 2012–2013
    • Anna University, Chennai
      • Department of Medical Physics
      Chennai, Tamil Nādu, India
  • 2011–2013
    • Hokkaido University
      • Graduate School of Life Science
      Sapporo-shi, Hokkaido, Japan
  • 2003–2007
    • Tokyo University of Technology
      • School of Bionics
      Edo, Tōkyō, Japan
  • 1993–2006
    • The University of Tokyo
      • Research Center for Advanced Science and Technology
      Tokyo, Tokyo-to, Japan
  • 2002
    • Bar Ilan University
      • Faculty of Life Sciences
      Ramat Gan, Tel Aviv, Israel
  • 1992
    • Research Institute of Innovative Technology for the Earth
      Kioto, Kyōto, Japan