詳細

古薗　勉 （フルゾノ　ツトム）

  • 生物理工学部 医用工学科　教授/学部長
Last Updated :2024/04/25

コミュニケーション情報 byコメンテータガイド

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    ナノテクノロジーによるバイオマテリアルを開発し、ベンチャー企業を立ち上げて医療機器製造・販売に係る事業化を行っています。また臨床では、我が国の在宅血液透析を推進しています。

  • 報道関連出演・掲載一覧

    ＜報道関連出演・掲載一覧＞ ●2023/6/22 　読売新聞（和歌山版） 　生物理工学部と自衛隊との連携協定締結について ●2023/2/3 　わかやま新報 　広域防災拠点に係る覚書締結について

研究者情報

学位

  • 博士（工学）（鹿児島大学）
  • 博士（医学）（大阪大学）

ホームページURL

J-Global ID

研究キーワード

  • 医療機器   人工臓器   生体材料   ナノ材料   セラミックス   生体機能材料   高分子   透析療法   

現在の研究分野（キーワード）

    ナノテクノロジーによるバイオマテリアルを開発し、ベンチャー企業を立ち上げて医療機器製造・販売に係る事業化を行っています。また臨床では、我が国の在宅血液透析を推進しています。

研究分野

  • ナノテク・材料 / ナノ材料科学
  • ライフサイエンス / 生体材料学
  • ライフサイエンス / 生体医工学

経歴

  • 2010年 - 現在  近畿大学生物理工学部医用工学科教授
  • 2000年 - 2010年  国立循環器病センター研究所研究室長
  • 2001年 - 2004年  国立研究開発法人科学技術振興機構さきがけ研究者（兼任）
  • 1999年 - 2000年  無機材質研究所NEDO提案公募研究員
  • 1997年 - 1999年  蚕糸・昆虫農業研究所COE特別研究員
  • 1996年 - 1997年  ワシントン大学バイオエンジニアリングセンター客員研究員

学歴

  • 2011年 - 2017年   大阪大学   医学部   心臓血管外科学講座 研究生
  • 1994年 - 1996年   鹿児島大学大学院   工学研究科   博士後期課程
  • 1993年 - 1994年   鹿児島大学   医学部   臨床検査医学講座 研究生
  • 1991年 - 1993年   鹿児島大学大学院   工学研究科修士課程
  • 1990年 - 1991年   鹿児島大学   工学部   応用化学科 研究生
  • 1984年 - 1984年   鹿児島大学大学院   農学研究科   修士課程
  • 1980年 - 1984年   鹿児島大学   農学部   農学科

所属学協会

  • 日本セラミックス協会   日本バイオマテリアル学会   日本人工臓器学会   日本透析医学会   アジア環太平洋人工臓器学会   日本生体医工学会   日本医工学治療学会   日本在宅血液透析学会   

研究活動情報

論文

  • In vitro evaluation of antibacterial-induced anaphylactoid reaction for indwelling catheters
    K. Umeda; M. Tachikawa; Y. Azuma; T. Furuzono
    Ren. Replace. Ther. 8 34 1 - 5 2022年08月 [査読有り]
  • Mari Oshita; Koji Umeda; Minami Kataoka; Yoshinao Azuma; Tsutomu Furuzono
    Journal of Biomaterials Applications 37 4 659 - 667 2022年06月 [査読有り]
     
    Percutaneous devices—indwelling catheters—related infections are serious clinical incidents. It is accordingly necessary to develop anti-infective coating materials suitable for the devices for long-term effectiveness. In our research group, highly dispersible and crystalline hydroxyapatite (HAp) nanoparticles doped with metallic or halogen ions possessing antibacterial activities have been developed. In this study, antibacterial, dispersible, and crystalline zinc (Zn)-doped hydroxyapatite [Zn(15)-HAp] nanoparticles substituted with 13.5% Zn content [Zn/(Zn + Ca) × 100] were prepared by a wet chemical method using an anti-sintering agent through calcination. Antibacterial activities of Zn(15)-HAp nanoparticles were evaluated using Escherichia coli ( E. coli) and Staphylococcus aureus. The survival rates of the bacteria on Zn(15)-HAp nanoparticles were significantly lower than that on normal HAp (nHAp) coated surfaces, while no influences were observed on proliferation of L929 cells. Even after soaking Zn(15)-HAp nanoparticles in PBS for 2 weeks, the antibacterial activities against E. coli were maintained at a similar level to a 20 min soaking. The bacterial death was related to not only ion-exchange phenomenon between Zn and magnesium ions but also accumulation of reactive oxygen species (ROS) in the cells. Allergic-like reactions—anaphylactoid reactions—might not readily occur with Zn(15)-HAp nanoparticles because the amounts of histamine released from HMC-1 cells co-cultured with nanoparticles were not significantly different to that of nHAp, but were statistically much lower than that of chlorhexidine.
  • Masanori Okada; Mari Oshita; Minami Kataoka; Yoshinao Azuma; Tsutomu Furuzono
    J. Biomed. Mater. Res.: Part B – Appl. Biomed. 110 4 799 - 805 2021年10月 [査読有り]
     
    Four types of zinc (Zn)-doped hydroxyapatite (Zn-HAp) nanoparticles were prepared using calcium nitrate tetrahydrate as an anti-sintering agent during calcination at 600°C for 1 hr, to prevent calcination-induced aggregation. The Zn content of the nanopowders was determined at 0, 4.3, 9.2, and 14.7% [Zn/(Ca + Zn) × 100] using inductively coupled plasma atomic emission spectroscopic analysis. Based on X-ray diffraction analysis, the products were shown to possess an apatite structure without other crystalline impurities. The cell parameters of Zn-HAp nanoparticles decreased with increasing of Zn content in the HAp structures. This tendency implies that Zn ions substituted for Ca sites in the HAp crystal lattices. To investigate the biological effects of Zn-HAp nanoparticles, cell proliferation activity of MC3T3-E1 osteoblasts and antibacterial activity against Escherichia coli were evaluated in vitro. According to the results obtained, Zn-HAp nanoparticles containing of 14.7% Zn ions was noticeable shown shareability of the conflicting activities at 0.1 mg/mL.
  • Antibacterial coating of titanium-doped hydroxyapatite nanoparticles on a polymer substrate
    M. Okazaki; Y. Azuma; M. Iwasaki; T. Furuzono
    Func. Mater. Lett. 14 4 2151014-1 - 6 2021年 [査読有り]
  • Evaluation of fluorinated hydroxyapatite nanoparticles as an antibacterial material for catheter coating
    H. Gyotoku; Y. Azuma; T. Furuzono
    Ren. Replace. Ther 6 3 1 - 8 2020年 [査読有り]
  • Tsutomu Furuzono; Masatoshi Okazaki; Yoshinao Azuma; Mitsunobu Iwasaki; Yasumichi Kogai; Yoshiki Sawa
    Contrib. Nephrol. 189 144 - 152 2017年 [査読有り]
     
    Background: Thirteen patients with chlorhexidine-silver sulfadiazine-impregnated catheters have experienced serious anaphylactic shock in Japan. These adverse reactions highlight the lack of commercially available catheters impregnated with strong antibacterial chemical agents. A system should be developed that can control both biocompatibility and antibacterial activity. Summary: Hydroxyapatite (HAp) is biocompatible with bone and skin tissues. To provide antibacterial activity by using an external physical stimulus, titanium (Ti) ions were doped into the HAp structure. Highly dispersible, Ti-doped HAp (Ti-HAp) nanoparticles suitable as a coating material were developed. In 3 kinds of Ti-HAp [Ti/(Ca + Ti) = 0.05, 0.1, 0.2], the Ti content in the HAp was approximately 70% of that used in the Ti-HAp preparation, as determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). ICP-AES and X-ray diffraction showed Ti ions were well substituted into the HAp lattice. The nanoparticles were almost uniformly coated on a polyethylene (PE) sheet in a near-monolayer with a surface coverage ratio > 95%. The antibacterial activity of the Ti-HAp nanoparticles containing 7.3% Ti ions and coating the sheet was evaluated by calculating the survival ratio of Pseudomonas aeruginosa on the coated sheet after ultraviolet (UV) irradiation. The Ti-HAp-coated sheet showed a 50% decrease in the number of P. aeruginosa compared with that on an uncoated control PE sheet after UV irradiation for 30 s. Key Messages: A system of biocompatibility and antibacterial activity with an on/off switch controlled by external UV stimulation was developed. The system is expected to be applicable in long-term implanted intravascular catheters.
  • Nobuhiro Kato; Yuka Hatoko; Ei Yamamoto; Tsutomu Furuzono; Shigeki Hontsu
    Key Engineering Materials 720 102 - 107 2017年 [査読有り]
     
    Potassium-substituted calcium phosphate free standing sheet for the treatment of dentin hypersensitivity was prepared and evaluated. The appropriate annealing condition for the target of pulsed laser deposition to prepare the potassium-substituted amorphous calcium phosphate (PS-ACP) sheet was investigated. The target annealed at 1000 �C was used to deposit the PS-ACP sheet. The annealing condition for the potassium-substituted hydroxyapatite (PS-HAp) sheet was evaluated by XRD and EDX. The potassium release rate from PS-ACP sheet in PBS, evaluated by ICP-MS, was 2.5 times larger than that of PS-HAp sheet. The robustness of the PS-ACP sheet was proved by the brushing test of the PS-ACP sheet affixed on a bovine dentin. The dentin tubules on the dentin surface was occluded by the PS-ACP sheet and which confirmed by SEM observations.
  • Tsutomu Furuzono; Yoshinao Azuma; Yuichi Niigawa; Yasumichi Kogai; Yoshiki Sawa
    ASAIO JOURNAL 62 2 197 - 202 2016年03月 [査読有り]
     
    To develop a nanoscaled coating material for medical devices possessing weak antibacterial activity, dispersible and crystalline fluorinated hydroxyapatite (F-HAp) nanoparticles were prepared using antisintering agent to avoid calcination-induced sintering. The product was identical to fluorapatite, as determined by X-ray diffraction and Fourier transform infrared spectroscopy. The primary particles generally showed rod-shaped morphology with a length of 367 +/- 67 nm and a width of 223 +/- 21 nm measured by scanning electron microscopy (SEM). The dispersed average particle size (313 +/- 51 nm) in ethanol analyzed by dynamic light scattering was almost the same as that obtained from the SEM images. In the evaluation of solubility in acidic aqueous solution, F-HAp and original hydroxyapatite (HAp) nanoparticles started to dissolve at around pH 3.4 and 4.2, respectively. Thus, the stability of F-HAp in a living body increased compared with original HAp. The antibacterial activity of F-HAp nanoparticles was higher than that of fluoride in sodium fluoride alone or the original HAp nanoparticles. However, it was estimated that the effect of F-HAp was much lower compared with that of silver, one of the popular antibacterial materials. Thus, the dispersed F-HAp nanoparticles possessing weak antimicrobial activity can be useful without severe damage to the living tissue.
  • 波床侑果; 山本衛; 加藤暢宏; 西川博昭; 吉川一志; 古薗勉; 山本一世; 本津茂樹
    日本歯科理工学会誌 34 5 416 - 416 (一社)日本歯科理工学会 2015年09月 [査読有り]
  • Tsutomu Furuzono; Mazumder Motaharul; Yasumichi Kogai; Yoshinao Azuma; Yoshiki Sawa
    INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS 38 5 251 - 258 2015年05月 [査読有り]
     
    Purpose: Dispersible hydroxyapatite (HAp) nanoparticles are very useful for applying a monolayer to implantable medical devices using the nano-coating technique. To improve tolerance to infection on implanted medical devices, silver-doped HAp (Ag-HAp) nanoparticles with dispersiblity and crystallinity were synthesized, avoiding calcination-induced sintering, and evaluated for antibacterial activity. Methods: The Ca10-xAgx(PO4)(6)(OH)(2) with x = 0 and 0.2 were prepared by wet chemical processing at 100 degrees C. Before calcination at 700 degrees C for 2 h, two kinds of anti-sintering agents, namely a Ca(NO3)(2) (Ca salt) and a polyacrylic acid/Ca salt mixture (PAA-Ca), were used. Escherichia coli was used to evaluate the antibacterial activity of the nanopowder. Results: When PAA-Ca was used as an anti-sintering agent in calcination to prepare the dispersible nanoparticles, strong metallic Ag peaks were observed at 38.1 degrees and 44.3 degrees (2 theta) in the X-ray diffraction (XRD) profile. However, the Ag peak was barely observed when Ca salt was used alone as the anti-sintering agent. Thus, using Ca salt alone was more effective for preparation of dispersible Ag-HAp than PAA-Ca. The particle average size of Ag-HAp with 0.5 mol% of Ag content was found to be 325 +/- 70 nm when the formation of large particle-aggregations was prevented, as determined by dynamic light scattering instrument. The antibacterial activity of the Ag-HAp nanoparticles possessing 0.5 mol% against E. coli was greater than 90.0%. Conclusions: Dispersible and crystalline nano Ag-HAp can be obtained by using Ca salt alone as an anti-sintering agent. The nanoparticles showed antibacterial activity.
  • カリウム含有HAp薄膜の作製および溶解性
    波床侑果; 西川博昭; 古薗 勉; 本津茂樹
    バイオインテグレーション学会誌 5 69 - 72 2015年 [査読有り]
  • Koji Takeda; Shinya Fukumoto; Koka Motoyama; Tomoaki Morioka; Katsuhito Mori; Ken Kageyama; Yukimasa Sakai; Hideki Sato; Masakazu Suzuki; Hidenori Koyama; Tetsuo Shoji; Eiji Ishimura; Masanori Emoto; Tsutomu Furuzono; Koichi Nakajima; Masaaki Inaba
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 454 1 119 - 124 2014年11月 [査読有り]
     
    The clinical success of cell-based therapeutic angiogenesis has been limited in diabetic patients with critical limb ischemia. We previously reported that an injectable cell scaffold (ICS), which is a nano-scaled hydroxyapatite (HAp)-coated polymer microsphere, enhances therapeutic angiogenesis. Subsequently, we developed a modified ICS for clinical use, measuring 50 mu m in diameter using poly(L-lactide-co-epsilon-caprolactone) as a biodegradable polymer, which achieved appropriately accelerated absorption in vivo. The aim of the present study was to evaluate the effectiveness of this practical ICS in diabetic hindlimb ischemia. Bone-marrow mononuclear cells (BMNCs) were intramuscularly injected, without or with a practical ICS, into the ischemic hindlimbs of mice (BMNCs or ICS + BMNCs group, respectively). Kaplan-Meier analysis demonstrated that the beneficial effects of BMNC transplantation for limb salvage after ischemic surgery were almost entirely abrogated in streptozotocin-induced diabetic mice. In contrast, injection of ICS + BMNCs revealed significant limb salvage in diabetic mice to a similar extent as in non-diabetic mice. The number of apoptotic transplanted BMNCs was 1.8-fold higher in diabetic mice 10 days after transplantation compared to non-diabetic mice, while that in the ICS + BMNCs group was markedly lower (8.3% of that in the BMNCs group) even in diabetic mice. The proangiogenic factors VEGF and FGF2, also known as antiapoptotic factors, mostly co-localized with transplanted GFP-positive BMNCs that were closely aggregated around the ICS in ischemic tissue. In conclusion, the practical ICS significantly augmented cell-based therapeutic angiogenesis even in diabetic animals, through local accumulation of proangiogenic factors and antiapoptotic effects in transplanted cells. (C) 2014 Elsevier Inc. All rights reserved.
  • Masahiro Okada; Yuko Omori; Mayuko Awata; Tsubasa Shirai; Naoyuki Matsumoto; Shoji Takeda; Tsutomu Furuzono
    JOURNAL OF NANOPARTICLE RESEARCH 16 7 2469 - 2477 2014年06月 [査読有り]
     
    We investigated the influence of calcination conditions to fabricate dispersible hydroxyapatite (HAp) nanocrystals via calcination with an anti-sintering agent, poly(acrylic acid, calcium salt) (PAA-Ca), surrounding the nanocrystals. First, two kinds of low crystallinity HAp nanoparticles with spherical morphology (58 nm in diameter) and rod-shaped morphology (around 350 nm in length) were synthesized by wet chemical processes, and then coated with PAA-Ca in aqueous media. The HAp/PAA-Ca mixture was dried and calcined at 800 or 1,000 A degrees C for 1 h. The resultant mixture was finally washed with aqueous media to remove CaO-the thermally decomposed product of PAA-Ca-surrounding the nanocrystals. The calcination-induced sintering between the nanocrystals was efficiently prevented by increasing the amount of PAA-Ca, but the increased amount of PAA-Ca also led to the formation of CaCO3 due to the incomplete thermal decomposition of PAA-Ca at 800 A degrees C for 1 h. Highly dispersible and phase pure HAp nanocrystals could be obtained by calcination at higher temperature (1,000 A degrees C). We also found that calcium ions were migrated from the anti-sintering agent into the HAp nanocrystals, and the degree of calcium ion migration varied by the nature of the low crystallinity HAp nanoparticles and the calcination temperature.
  • Tetsushi Taguchi; Masahiro Okada; Yasumichi Kogai; Miwa Masuda; Yumi Shimomura; Motoki Inoue; Temmei Ito; Takashi Hamahata; Keiji Funatogawa; Teruo Kirikae; Tsutomu Furuzono
    JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS 29 3 284 - 297 2014年03月 [査読有り]
     
    A new material was prepared to reduce catheter infection composed of a flocked silicone sheet (AmTiO2NP-F) with TiO2 nanoparticle-immobilized poly(ethylene terephthalate) fibers modified with surface amino groups. This system was used in conjunction with a tissue adhesive composed of disuccinimidyl tartrate and human serum albumin. At a fixed disuccinimidyl tartrate content of 0.2 mmol in human serum albumin solution, AmTiO2NP-F bonded well with collagen-based casing (a model material for skin), with bond strength increasing to a maximum of 38 w/v% human serum albumin. The adhesive bonded AmTiO2NP-F to subcutaneous tissue in mice, and infiltration of the tissue into the AmTiO2NP-F further increased the bond strength for long-term insertions. The material was degraded within 7 days of implantation, and tissue reaction was mild, while infection was completely prevented. These results indicate that the combined use of AmTiO2NP-F and disuccinimidyl tartrate-A for implanted catheters can significantly alleviate the associated risk of infection.
  • Tsutomu Furuzono; Takashi Iwamoto; Yoshinao Azuma; Masahiro Okada; Yoshiki Sawa
    JOURNAL OF ARTIFICIAL ORGANS 16 4 451 - 457 2013年12月 [査読有り]
     
    Carboxyl group-donated silver (Ag) nanoparticles for coating on medical devices were prepared by a two-phase reduction system in situ. AgNO3 was the Ag ion source, tetraoctylammonium bromide [N(C8H17)(4)Br] the phase-transfer agent, sodium tetrahydroborate (NaBH4) the reducing agent and 10-carboxy-1-decanthiol (C11H22O2S, CDT) the capping agent. The characterizations of the Ag nanoparticles were conducted by diffuse reflectance Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric differential thermal analysis (TG/DTA) and transmission electron microscope. With CDT capped on Ag nanoparticles, we found that the band around 3,100 cm(-1) was attributed to COO-H stretching vibration, two adsorptions at 2,928 and 2,856 cm(-1) to C-H symmetric/anti-symmetric stretching vibration, and at 1,718 cm(-1) to C=O stretching vibration in the FT-IR spectra. The organic components of the carboxylated Ag nanoparticles were 5.8-25.9 wt%, determined by TG/DTA. The particle sizes of the carboxylated Ag nanoparticles were well controlled by the addition of the capping agent, CDT, into the reaction system. The antimicrobial activity of the Ag nanoparticles covered with different contents of CDT against E. coli was evaluated. Smaller-size Ag nanoparticles showed higher antibacterial activity, which depended on a surface area that attached easily to a microorganism cell membrane.
  • Hiroyuki Shinto; Takuya Hirata; Tomonori Fukasawa; Syuji Fujii; Hayata Maeda; Masahiro Okada; Yoshinobu Nakamura; Tsutomu Furuzono
    COLLOIDS AND SURFACES B-BIOINTERFACES 108 8 - 15 2013年08月 [査読有り]
     
    We have measured the interaction forces between a murine melanoma cell and a poly(L-lactic acid) (PLLA) microsphere coated with/without hydroxyapatite (HAp) nanoparticles (i.e., an HAp/PLLA or a bare PLLA microsphere) in a serum-free culture medium, using atomic force microscopy (AFM) with colloid probe technique, in order to investigate how the HAp-nanoparticle coating as well as interfacial serum proteins influence the cell microsphere adhesion. The cell adhesion force of the HAp/PLLA microspheres was 1.4-fold stronger than that of the bare PLLA microspheres. When the microspheres were pretreated with a culture medium supplemented with 10% fetal bovine serum, the cell adhesion force of the HAp/PLLA microspheres was increased by a factor of 2.1; in contrast, no change was observed in the cell adhesion force of the bare PLLA microspheres before/after the pretreatment. Indeed, the cell adhesion force of the HAp/PLLA was 2.8-fold larger than that of the bare PLLA after the pretreatment. Additionally, we have investigated the effect of interfacial serum proteins on the zeta potentials of these microspheres. On the basis of the obtained results, possible mechanism of cell adhesion to the HAp/PLLA and bare PLLA microspheres in the presence/absence of the interfacial serum proteins is discussed. (C) 2013 Elsevier B.V. All rights reserved.
  • S. Fujii; M. Okada; T. Nishimura; T. Sugimoto; H. Maeda; H. Hamasaki; T. Furuzono; Y. Nakamura
    Composite Interfaces 20 1 45 - 56 2013年02月 [査読有り]
     
    Hydroxyapatite (HAp) nanoparticle-coated poly(E-caprolactone) (PCL) microspheres were fabricated via surfactant-free Pickering-type' emulsion solvent evaporation method in the absence of any molecular surfactants. HAp nanoparticles worked as an efficient stabilizer for dispersion of emulsions and microspheres. Optical microscopy, scanning electron microscopy, laser diffraction particle size analyzer, and elemental analysis were used to characterize the microspheres in terms of their size, dispersibility in aqueous media, morphology of the microspheres, and chemical compositions. The microsphere size and PCL/HAp weight ratio were successfully controlled by fabrication parameters (PCL concentration in the oil phase, HAp nanoparticle concentration in the aqueous phase, and homogenization rate): number-average diameter of the microspheres was systematically controlled over a wide range (9.225.1m) and PCL/HAp weight ratio was controlled to be between 74.0/26.0 and 99.8/0.2. Laser diffraction and optical microscopy studies of dilute aqueous dispersions indicate that the polymer microspheres disperse stably before and after evaporation of the oil. Potential applications for these HAp-coated PCL microspheres include carriers for cell delivery in tissue engineering and for sustained release of therapeutics.
  • Syuji Fujii; Yuki Miyanari; Taiki Nishimura; Yuichi Yokoyama; Sho Hamasaki; Masahiro Okada; Tsutomu Furuzono; Shojiro Matsuda; Hideki Takamori; Yoshinobu Nakamura
    POLYMER DEGRADATION AND STABILITY 98 1 377 - 386 2013年01月 [査読有り]
     
    In vitro degradation behavior of hydroxyapatite (HAp) nanoparticle-coated poly(L-lactide-co-epsilon-caprolactone) (PLCL) microspheres, which were fabricated via 'Pickering emulsion' route, has been examined in terms of weight, molecular weight, thermal property, and morphological changes through incubation in a phosphate buffered saline up to 48 weeks. Gel permeation chromatography, scanning electron microscopy (SEM) and gravimetrical method were employed to characterize their degradation profiles. It was found that molecular weight of PLCL decreased rapidly after immersing the microspheres in the buffered saline and, on the other hand, the weight of the microspheres started to decrease after 16 weeks. These results support bulk degradation for the HAp-coated PLCL microspheres. During the degradation, the enthalpy of melting increased progressively, which should be due to the increase of crystallinity because of chain rearrangement of amorphous region induced by water uptake and the preferential degradation of amorphous regions. The microspheres retained spherical morphology at least for 48 weeks and the HAp nanoparticles detached from the microsphere surface, which was confirmed by SEM study. The microspheres were easy to be broken by external pressure when the molecular weight became below 35,000 g/mol after 24-week incubation. (C) 2012 Elsevier Ltd. All rights reserved.
  • Masahiro Okada; Syuji Fujii; Taiki Nishimura; Yoshinobu Nakamura; Shoji Takeda; Tsutomu Furuzono
    APPLIED SURFACE SCIENCE 262 39 - 44 2012年12月 [査読有り]
     
    Hydroxyapatite (HAp) nanoparticle-coated biodegradable polymer particles were fabricated from a nanoparticle-stabilized emulsion in the absence of any molecular surfactants or organic solvents. First, a polymer melt-in-water emulsion was prepared by mixing a water phase containing nanosized HAp particles as a particulate emulsifier and an oil phase consisting of poly(epsilon-caprolactone) (PCL) or poly(L-lactide-co-epsilon-caprolactone) (P(LLA-CL)) above its melting point. It was clarified that the interaction between ester/carboxyl groups of the polymers and the HAp nanoparticles at the polymer-water interface played a crucial role to prepare the nanoparticle-stabilized emulsion. The HAp nanoparticle-coated biodegradable polymer particle (a polymer solid-in-water emulsion) was fabricated by cooling the emulsion. The particle morphology and particle size were evaluated using scanning electron microscope. (c) 2012 Elsevier B.V. All rights reserved.
  • M. Okada; S. Takeda; T. Furuzono
    Key. Eng. Mater. 529-530 223 - 228 2012年11月 
    HAp-nanoparticle-coated biodegradable polymer microspheres loaded with magnetic Fe3O4 particles can be successfully prepared by evaporating volatile oil (dichloromethane) from HAp-nanoparticle-stabilized oil droplets containing biodegradable polymer and Fe3O4 particles without any molecular surfactants or polymeric stabilizers. In this study it was found that the hydrophobic surface modification for the Fe3O4 particles was a key factor to prepare stable HAp-nanoparticle-stabilized oil droplets (and HAp-nanoparticle-coated polymer microspheres) loaded with magnetic Fe3O4 particles.
  • Takashi Iwamoto; Takahiro Terada; Yasumichi Kogai; Masahiro Okada; Syuji Fujii; Tsutomu Furuzono
    FUNCTIONAL MATERIALS LETTERS 5 2 1 - 6 2012年06月 [査読有り]
     
    We prepared poly(L-lactide-co-glycolide) cell scaffolds coated with hydroxyapatite (HAp) nanocrystals with 50 100 nm in diameter via the Pickering emulsion method. Our cell scaffolds were composed of biodegradable polymers and HAp nanocrystals as a core and shell, respectively. The scaffolds were spherical but displayed uneven shapes when altering a shear speed of homogenization during syntheses. The surface coverage of HAp nanocrystals was examined because the HAp-coating ratio for the scaffolds was an important factor as cell scaffolds in order to enhance cell adhesion. On the basis of scanning electron microscopy observations and thermogravimetric analyses, it was found that the cell scaffolds showed distorted morphologies, and the HAp-coating ratio decreased with increasing the shear speed in the synthesis because shear stress influenced shapes of the scaffolds.
  • Masahiro Okada; Hayata Maeda; Syuji Fujii; Yoshinobu Nakamura; Tsutomu Furuzono
    LANGMUIR 28 25 9405 - 9412 2012年06月 [査読有り]
     
    The influence of end groups of a polymer dissolved in an oil phase on the formation of a Pickering-type hydroxyapatite (HAp) nanoparticle-stabilized emulsion and on the morphology of HAp nanoparticle-coated microspheres prepared by evaporating solvent from the emulsion was investigated. Polystyrene (PS) molecules with varying end groups and molecular weights were used as model polymers. Although HAp nanoparticles alone could not function as a particulate emulsifier for stabilizing dichloromethane (oil) droplets, oil droplets could be stabilized with the aid of carboxyl end groups of the polymers dissolved in the oil phase. Lower-molecular-weight PS molecules containing carboxyl end groups formed small droplets and deflated microspheres, due to the higher concentration of carboxyl groups on the droplet/microsphere surface and hence stronger adsorption of the nanoparticles at the water/oil interface. In addition, Pickering-type suspension polymerization of styrene droplets stabilized by PS molecules containing carboxyl end groups successfully led to the formation of spherical HAp-coated microspheres.
  • Syuji Fujii; Masahiro Okada; Taiki Nishimura; Hayata Maeda; Tatsuya Sugimoto; Hiroyuki Hamasaki; Tsutomu Furuzono; Yoshinobu Nakamura
    JOURNAL OF COLLOID AND INTERFACE SCIENCE 374 1 - 8 2012年05月 [査読有り]
     
    Hydroxyapatite (HAp) nanoparticle-armored poly(epsilon-caprolactone) (PCL) microspheres were fabricated via a "Pickering-type" emulsion solvent evaporation method in the absence of any molecular surfactants. It was clarified that the interaction between carbonyl/carboxylic acid groups of PCL and the HAp nanoparticles at an oil-water interface played a crucial role in the preparation of the stable Pickering-type emulsions and the HAp nanoparticle-armored microspheres. The HAp nanoparticle-armored PCL microspheres were characterized in terms of size, size distribution, morphology, and chemical compositions using scanning electron microscopy, laser diffraction, energy dispersive X-ray microanalysis, and thermogravimetric analysis. The presence of HAp nanoparticles at the surface of the microspheres was confirmed by scanning electron microscopy and energy dispersive X-ray microanalysis. Pyrolysis of the PCL cores led to the formation of the corresponding HAp hollow microcapsules. (C) 2012 Elsevier Inc. All rights reserved.
  • Yohei Mima; Shinya Fukumoto; Hidenori Koyama; Masahiro Okada; Shinji Tanaka; Tetsuo Shoji; Masanori Emoto; Tsutomu Furuzono; Yoshiki Nishizawa; Masaaki Inaba
    PLOS ONE 7 4 1 - 12 2012年04月 [査読有り]
     
    Background: Clinical trials demonstrate the effectiveness of cell-based therapeutic angiogenesis in patients with severe ischemic diseases; however, their success remains limited. Maintaining transplanted cells in place are expected to augment the cell-based therapeutic angiogenesis. We have reported that nano-hydroxyapatite (HAp) coating on medical devices shows marked cell adhesiveness. Using this nanotechnology, HAp-coated poly(L-lactic acid) (PLLA) microspheres, named nano-scaffold (NS), were generated as a non-biological, biodegradable and injectable cell scaffold. We investigate the effectiveness of NS on cell-based therapeutic angiogenesis. Methods and Results: Bone marrow mononuclear cells (BMNC) and NS or control PLLA microspheres (LA) were intramuscularly co-implanted into mice ischemic hindlimbs. When BMNC derived from enhanced green fluorescent protein (EGFP)-transgenic mice were injected into ischemic muscle, the muscle GFP level in NS+BMNC group was approximate fivefold higher than that in BMNC or LA+BMNC groups seven days after operation. Kaplan-Meier analysis demonstrated that NS+BMNC markedly prevented hindlimb necrosis (P < 0.05 vs. BMNC or LA+BMNC). NS+BMNC revealed much higher induction of angiogenesis in ischemic tissues and collateral blood flow confirmed by three-dimensional computed tomography angiography than those of BMNC or LA+BMNC groups. NS-enhanced therapeutic angiogenesis and arteriogenesis showed good correlations with increased intramuscular levels of vascular endothelial growth factor and fibroblast growth factor-2. NS co-implantation also prevented apoptotic cell death of transplanted cells, resulting in prolonged cell retention. Conclusion: A novel and feasible injectable cell scaffold potentiates cell-based therapeutic angiogenesis, which could be extremely useful for the treatment of severe ischemic disorders.
  • Hydroxyapatite nanoparticles: fabrication methods and medical applications
    M. Okada; T. Furuzono
    Sci. Technol. Adv. Mater. 13 6 1 - 14 2012年
  • Hiroshi Yanagida; Masahiro Okada; Miwa Masuda; Isao Narama; Shigeyuki Nakano; Satoshi Kitao; Kazuo Takakuda; Tsutomu Furuzono
    JOURNAL OF ARTIFICIAL ORGANS 14 4 331 - 341 2011年12月 [査読有り]
     
    A novel hydroxyapatite (HAp)/poly(l-lactic acid) (PLLA) nanocomposite nonwoven fabric, which was coated and mixed with calcined HAp nanocrystals, and has submicron-sized dimples on its surface, was fabricated. First, HAp-mixed PLLA fabric was prepared by electrospinning a HAp nanocrystal dispersion in dichloromethane (DCM)-dissolved PLLA. It was found that most of the HAp nanocrystals were not exposed on the HAp-mixed PLLA fiber surface but covered with the PLLA matrix. A HAp-nanocrystal coating was applied onto the surface of the HAp-mixed PLLA fabric after corona discharge treatment followed by ethanol washing. The submicron-sized dimples were enlarged after the ethanol washing. After the HAp-nanocrystal coating, the HAp-mixed PLLA fabric surface was uniformly coated with the HAp nanocrystals. In vitro cell spread tests showed that the rat osteoblasts spread more on HAp-nanocrystal-coated fabrics than on non-HAp-coated fabrics. Upon covering calvarial defects, the in vivo hard tissue responses suggested earlier restoration of the defects with HAp-nanocrystal-coated fabrics than those with non-HAp-coated fabrics.
  • Masahiro Okada; Tsutomu Furuzono
    JOURNAL OF COLLOID AND INTERFACE SCIENCE 360 2 457 - 462 2011年08月 [査読有り]
     
    The conditions for preparing transparent blocks assembled with low-crystallized hydroxyapatite (HAp) nanoparticles were examined. An aqueous dispersion of 32-nm-sized HAp nanoparticles was prepared by a wet chemical process at room temperature (18-22 degrees C), and then the nanoparticle-assembled block was prepared by casting the dispersion at 60 degrees C. We also proposed a novel casting method on flowable substrates to fabricate crack-free nanoparticle-assembled blocks, because large and thick blocks were not obtained by a conventional casting method on solid substrates due to crack formation. The nanoparticle-assembled transparent HAp had nanosized pores among the particles. Cell adhesion and proliferation on the block could be directly observed with an optical microscope. (C) 2011 Elsevier Inc. All rights reserved.
  • Shingo Mutsuo; Kazuya Yamamoto; Tsutomu Furuzono; Tsuyoshi Kimura; Tsutomu Ono; Akio Kishida
    JOURNAL OF APPLIED POLYMER SCIENCE 119 5 2725 - 2729 2011年03月 [査読有り]
     
    Our previous research showed that a simple ultra-high-pressure process made poly(vinyl alcohol) (PVA) solution into a macrogel and nanoparticles. To investigate the release properties of PVA hydrogels prepared by the ultra-high-pressure treatment, we prepared hydrogels containing model drugs by pressurizing a PVA solution with Alfa-G Hesperidin or Oil Blue N as a water-soluble or an oil-soluble model drug, respectively. In the case of the oil-soluble drug, an oil-in-water emulsion, Oil Blue N containing dodecane in a PVA solution, was used by homogenization before pressurization. The average diameter and the diameter distribution of oil droplets before and after the ultra-high-pressure treatment were almost the same. However, the PVA hydrogel prepared at 10,000 atm for 10 min exhibited the slowest release rate of model drugs. Thus, we found that the release rates of the model drugs from the PVA hydrogels were controlled by the degree of crosslinking in the resulting gels, which was determined from the operation parameters of the ultrahigh-pressure treatment, such as the pressure, time, and concentration of the PVA solution. Therefore, an ultrahigh-pressure process is promising for drug-carrier development because of the nonharmful simple preparation process. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 2725-2729, 2011
  • Xiangwen Liu; Masahiro Okada; Hayata Maeda; Syuji Fujii; Tsutomu Furuzono
    ACTA BIOMATERIALIA 7 2 821 - 828 2011年02月 [査読有り]
     
    Hydroxyapatite (HAp)/biodegradable poly(L-lactide-co-epsilon-caprolactone) (P(LA/CL)) composite microparticles were fabricated as an injectable scaffold via the Pickering emulsion route in the absence of any molecular surfactants. A stable oil in water emulsion was obtained using water dispersed HAp nanocrystals as the particulate emulsifier and a dichloromethane (CH2Cl2) solution of P(LA/CL) as the oil phase. The concentration-viscosity relationship of the P(LA/CL) solution and its influence on the formation of a stable emulsion were investigated. The dependence of homogenization on the concentration of the P(LA/CL) solution and shear speed of homogenization was also evaluated. HAp/P(LA/CL) microparticles of various morphologies, such as plates and spheres, or with various surface morphologies were realized through adjustment of the concentration and composition of the P(LA/CL) solution. The microparticles were observed by optical microscopy and scanning electronic microscopy and their size distributions measured using a microparticle size analyzer. The weight percentages of HAp nanocrystals on the HAp/P(LA/CL) microparticles of different average sizes were measured by thermogravimetric analysis. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
  • Synthesis of Hydroxyapatite Nanocrystals and Their Application as Coating Agents for Biodegradable Polymers
    M. Okada; S. Takeda; T. Furuzono
    Proceedings of the International Dental Materials Congress 2011 155 - 155 2011年 [査読有り]
  • Preparation of Nanoscaled Ploy(viniyl alcohol)/Hydorxyapatite/DNA Complex Using High Hydrostatic Pressure Technology for In Vitro and In Vivo Gene Delively
    T. Kimura; Y. Nibe; S. Funamoto; M. Okada; T. Furuzono; T. Ono; H. Yoshizawa; T. Fujisato; K. Nam; A. Kishida
    J. Drug Delivery 2011 962743 1 - 8 2011年 [査読有り]
  • Masahiro Okada; Tsutomu Furuzono
    MATERIALS SCIENCE AND ENGINEERING B-ADVANCED FUNCTIONAL SOLID-STATE MATERIALS 173 1-3 199 - 203 2010年10月 [査読有り]
     
    Nano-sized single crystals of calcined hydroxyapatite (HAp) were uniformly coated on poly(L-lactic acid) (PLLA) microspheres through the ionic interaction between calcium ions on the HAp nanocrystal and carboxyl groups on the PLLA microsphere. In order to coat the substrate with HAp nanocrystals through ionic interaction, the surfaces of the PLLA microspheres were hydrolyzed in an alkaline aqueous solution at pH 11.0 for 1 h at room temperature. The interaction between the HAp nanocrystals and the carboxyl groups originating from PLLA end groups was estimated by Fourier transform infrared spectroscopy. The alkali-treated PLLA microspheres were coated with HAp nanocrystals by immersing the microspheres in an ethanol dispersion of HAp nanocrystals followed by washing in an ultrasonic bath. (C) 2009 Elsevier B.V. All rights reserved.
  • T. Furuzono; M. Masuda; N. Nitta; A. Kaya; T. Yamane; M. Okada
    Mater. Sci. Eng. B 173 1-3 191 - 194 2010年10月 [査読有り]
     
    It is recently known that titanium dioxide (TiO2) can be excited by ultrasound and release of OH radicals on the surface. In this study, secretion of an indirect angiogenic factor, tumor necrosis factor-alpha (TNF-alpha), from bone marrow mononuclear cells (BM-MNC) incubated on amino group modified TiO2 nanoparticles covalently coated on polyester fabric (TiO2/PET) under ultrasonic irradiation was examined in vitro. The cell viability and TNF-a secretion were measured under ultrasound irradiation condition with 255 mW/cm(2) of intensity, which is below the highest output (1 W/cm(2)) specified in the safety standard for a medical ultrasonic diagnostic apparatus. The living cell number on the TiO2/PET and original PET with/without continuous ultrasound irradiation was unchanged statistically by ANOVA test. TNF-alpha secretion level from BM-MNC remarkably increased on the TiO2/PET under ultrasonic irradiation without cell damage. It was, therefore, thought that the high level of TNF-alpha secretion on the TiO2 nano-composite by ultrasound irradiation was due to oxidative stress induced from OH radicals on TiO2. (C) 2009 Elsevier B.V. All rights reserved.
  • Hayata Maeda; Masahiro Okada; Syuji Fujii; Yoshinobu Nakamura; Tsutomu Furuzono
    LANGMUIR 26 17 13727 - 13731 2010年09月 [査読有り]
     
    Multihollow hydroxyapatite (HAp)/poly(L-lactic acid) (PLLA) nanocomposite microspheres were readily fabricated by solvent evaporation from a "Pickering-type" water-in-(dichloromethane solution of PLLA)-in-water multiple emulsion stabilized with HAp nanoparticles. The multiple emulsion was stabilized with the aid of PLLA molecules used as a wettability modifier for HAp nanoparticles, although HAp nanoparticles did not work solely as particulate emulsifiers for Pickering-type emulsions consisting of pure dichloromethane and water. The interaction between PLLA and HAp nanoparticles at the oil-water interfaces plays a crucial role toward the preparation of stable multiple emulsion and multihollow microspheres.
  • 古薗 勉; 森 義博; 太田雅顕; 長谷川晋也; 坂巻正倫; 松本良平; 横山和巳; 坂井瑠実
    透析会誌 43 325 - 328 2010年 [査読有り]
  • Hiroyuki Kadono; Tsutomu Furuzono; Miwa Masuda; Masahiro Okada; Mitsuki Ueki; Keiichi Takamizawa; Ryoichi Tanaka; Kunio Miyatake; Yoshihisa Koyama; Kazuo Takakuda
    ASAIO JOURNAL 56 1 61 - 66 2010年01月 [査読有り]
     
    The efficacy of hydroxyapatite (HAp) nanocoating on polyester vascular grafts was investigated in animal experiments. The HAp nanocrystals were covalently bonded separately between hydroxyl groups on a nanocrystal and alkoxysilyl groups in gamma-methacryloxypropyl triethoxysilane graft polymerized on a polyester substrate. Twelve HAp-coated polyester grafts and 10 control grafts of 20, 30, or 50 mm in length were implanted in canine common carotid arteries. Serious complications or occlusions were not observed in any of the dogs after implantation. A histologic evaluation was conducted by staining with hematoxylin and eosin (HE), the von Willebrand factor (vWf), and alpha-smooth muscle actin (alpha-SMA) around the inner lumen of the grafts. The number of inflammation cells and giant cells in the HAp-coated group was significantly lower than that in the group receiving noncoated grafts (p < 0.05). ASAIO Journal 2010; 56:61-66.
  • Naotaka Nitta; Akio Kaya; Takashi Yamane; Koji Hyodo; Masahiro Okada; Tsutomu Furuzono
    JAPANESE JOURNAL OF APPLIED PHYSICS 49 7 07HF24-1 - 7 2010年 [査読有り]
     
    It has been reported that the hydroxyl (OH) radical is produced by irradiating ultrasound to titanium dioxide (TiO2). On the other hand, infection at the exit site of catheter retained in the body has become a serious problem. Therefore, we are developing a novel anti-infective catheter system in which the exit site of a catheter is covered with an aminated titanium dioxide (AmTiO2) composite, which consists of AmTiO2 nanoparticles immobilized on a substrate and exhibits cell adhesiveness, and the anti-infective effect (OH radical production) is induced by irradiating low-intensity focused ultrasound (LIFU) to the composite. In this study, the ability to activate TiO2 nanoparticles by ultrasound irradiation was verified in a preliminary experiment, and then the feasibilities that the AmTiO2 composite is activated and that the OH radical is produced by LIFU irradiation were verified by dye decomposition experiment and dihydroxybenzoic acid (DHBA) measurement. In addition, as a trigger for activating the AmTiO2 composite by LIFU irradiation and for producing the OH radical, the decrease in cavitation threshold was suggested. (C) 2010 The Japan Society of Applied Physics
  • Hiroshi Yanagida; Masahiro Okada; Miwa Masuda; Mitsuki Ueki; Isao Narama; Satoshi Kitao; Yoshihisa Koyama; Tsutomu Furuzono; Kazuo Takakuda
    JOURNAL OF BIOSCIENCE AND BIOENGINEERING 108 3 235 - 243 2009年09月 [査読有り]
     
    Cell adhesion and tissue response to poly(L-lactic acid) (PLLA) fabric coated with nanosized hydroxyapatite (HAp) crystals were studied. The HAp nanocrystals were prepared by the wet chemical process followed by calcination at 800 degrees C with an anti-sintering agent to prevent calcination-induced sintering. After the PLLA fabric was hydrolyzed with an alkaline aqueous solution, the HAp nanocrystals were coated via ionic interaction between the calcium ions on the HAp and the carboxyl groups on the alkali-treated PLLA. The PLLA surface uniformly coated with the HAp nanocrystals was observed by scanning electron microscope. The ionic interaction between the HAp and the PLLA was estimated by FT-IR. Improved cell adhesion to the HAp nanocrystal-coated surface was demonstrated by in vitro testing using a mouse fibroblast cell line L929. Furthermore, reduced inflammatory response to the HAp nanocrystal-coated PLLA fabric (as compared with a non-treated one) was confirmed by a subcutaneous implantation test with rats. Thus the HAp nanocrystal-coated PLLA developed has possible efficacy as an implant material in the fields of general and orthopedic surgery, and as a cell scaffold in tissue engineering. (C) 2009, The Society for Biotechnology, Japan. All rights reserved.
  • Syuji Fujii; Masahiro Okada; Hidekatsu Sawa; Tsutomu Furuzono; Yoshinobu Nakamura
    LANGMUIR 25 17 9759 - 9766 2009年09月 [査読有り]
     
    Hydroxyapatite (HAp) nanoparticle-coated micrometer-sized poly(L-lactic acid) (PLLA) microspheres were fabricated via a "Pickering-type" emulsion route in the absence of Lilly molecular surfactants. Stable oil-in-water emulsions were prepared using 40 nm HAp nanoparticles as a particulate emulsifier and a dichloromethane (CH(2)Cl(2)) Solution of PLLA as an oil phase. It wits clarified that the interaction between carbonyl/carboxylic acid groups of PLLA and the HAp nanoparticles tat the CH(2)Cl(2)-water interface played a crucial role to prepare the stable Pickering-type emulsion. The HAp nanoparticle-coated PI L,A microspheres were fabricated by the evaporation of CH(2)Cl(2) from the emulsion and characterized in terms of size, particle size distribution. and morphology using scanning/transmission electron microscopes. Scanning electron microscopy study and ultrathin cross section observation using transmission electron microscopy confirmed adsorption of the HAp nanoparticles only at the surface of the PLLA microspheres. Cell-adhesion experiments suggested the HAp nanoparticles on the surface of the PLLA microspheres promoted the cell adhesion and spreading.
  • Tsutomu Furuzono; Mltsuki Ueki; Harumi Kitamura; Kazumasa Oka; Enyu Imai
    Journal of Biomedical Materials Research - Part B Applied Biomaterials 89 1 77 - 85 2009年04月 [査読有り]
     
    Rapid tissue-Ingrowth of a sintered hydroxyapatite(HAp)-coated and cell-hybrid subcutaneous cuff equipped with an Indwelling catheter was developed. The rod-like HAp nanoparticles were coated by covalent bonding on the surface of the silk fibroin (SF) fibers for about 100 μm of the length. The fibers were transplanted three-dintensionally on a cuff substrate made of silicone elastomer with an adhesive. The fibroblast-MIke cells, explanted and proliferated from skin tissue containing the epidermis, dermis, and subcutaneous tissue of Japanese white rabbits, were Incubated on the three-dimensional cuff for three days. Three types of cuff-polyester, HAp-coated, and cell-hybrid cuffs-were percutaneously implanted Into the backs of the same animals for 3 and 7 days. The subcutaneous tissues around the cuffs were stained with hematoxylin-eosin. Immunohisto chemical staining to identify macrophages and α-smooth muscle actin (α-SMA) was also done and examined by light microscopy. The α-SMA-positive area was very limited in the polyester cuff group even after 7 days, although many macrophages infiltrated into the fibers. In the cell-hybrid cuff group, on the other hand, an α-SMA-positive area was formed extensively after 3 and 7 days, causing severe inflammation. In the HAp-coated cuff group, an α-SMA-positive area was formed among the fibers with little inflammation. The extent order of the α-SMA-positive area was cell-hybrid cuff » HAp-coated cuff » polyester cuff, while the degree of inflammatory cells order was cell-hybrid cuff » polyester cuff » HAp-coated cuff. © 2008 Wiley Periodicals, Inc.
  • Interfacial interactions between calcined hydroxyapatite nanocrystals and substrates
    M. Okada; K. Furukawa; T. Serizawa; Y. Yanagisawa; H. Tanaka; T. Kawai; T. Furuzono
    Langmuir 25 11 6300 - 6306 2009年 [査読有り]
  • Mitsunobu Iwasaki; Yuki Miyamoto; Seishi Ito; Tsutomu Furuzono; Won-Kyu Park
    JOURNAL OF COLLOID AND INTERFACE SCIENCE 326 2 537 - 540 2008年10月 [査読有り]
     
    Nanometer-sized TiO2 island structure on the platy hydroxyapatite nanocrystals (HAp) has been accomplished by two-step emulsion process. At the first step, platy HAp nanocrystals, of which size was in the range of 70-200 nm after heat-treatment at 1078 K for 1 h, were prepared using the W/O emulsion system. Before the second step, HAp nanocrystals were immersed in NaH2PO4 solution for the formation of hydroxyl group on their surface. In the following, titanium tetraisopropoxide reacted with the hydroxyl group of HAp surface to form TiO2 nanoparticles on the surface of HAp nanocrystals, which were dispersed in the micrometer-sized methanol droplets of polyethylene cetylether-cyclohexane mixture (methanol/oil emulsion). The resulting hydroxyapatite nanocrystals loaded with TiO2 nanoparticles showed the high photocatalytic activity comparing to the commercial TiO2 catalyst. (C) 2008 Elsevier Inc. All rights reserved.
  • Masahiro Okada; Miwa Masuda; Ryoichi Tanaka; Kunio Miyatake; Daisuke Kuroda; Tsutomu Furuzono
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 86A 3 589 - 596 2008年09月 [査読有り]
     
    Calcined nanocrystals of hydroxyapatite (HAp) having spherical or rod-shaped morphologies were coated through covalent linkage on a type 316L stainless steel substrate, which was chemically modified by the graft polymerization of gamma-methacryloxypropyl triethoxysilane (MPTS) at 70-110 degrees C. The grafting of poly(MPTS) on the substrate was confirmed by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR). In order to coat the substrate with the HAp crystals through covalent linkage, the reaction between the alkoxysilyl groups in the poly (MPTS) grafted on the substrate and the OH groups on the HAp crystals was conducted at 80 degrees C. The poly(MPTS)grafted substrate was strongly coated with the HAp nano-crystals, although the HAp crystals adsorbed physically on the original substrate without poly(MPTS) grafting were removed by ultrasonic treatment. Human umbilical vein endothelial cells (HUVEC) adhered in larger numbers on the HAp-coated stainless steel substrate as compared with the original substrate after 24 h of initial incubation. The number of HUVEC adhered on the rod-shaped HAp-coated substrate was not significantly different from that on the spherical HAp-coated substrate under the present conditions. (c) 2007 Wiley Periodicals, Inc.
  • Shingo Mutsuo; Kazuya Yamamoto; Tsutomu Furuzono; Tsuyoshi Kimura; Tsutomu Ono; Akio Kishida
    JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS 46 7 743 - 750 2008年04月 [査読有り]
     
    Controlling the noncovalent bondings such as electrostatic interaction, van der Waals force and hydrogen bond, is the key factor to generate molecular assembly. We show that pressure is one of the most intensive variables for controlling these intermolecular forces and producing assembled structure. Macrogel and nanoparticles of hydrogen-bonded polymers were simply obtained through an ultrahigh-pressure process. The morphology of the obtained assembly depends on concentration and various conditions of the pressurization. These results indicate that the ultrahigh-pressure induces inter/intra-hydrogen bond, which is strong enough to maintain microassemblies such as gels and particles. This methodology leads to the molecular design of pressure-induced molecular assembly, and nonharmful processes for molecular separation and drug development.(C) 2008 Wiley Periodicals, Inc.
  • Atsutomo Nakamura; Atsumasa Shishido; Ippei Kishida; Masahiro Okada; Tsutomu Furuzono; Yoshiyuki Yokogawa
    Journal of the Ceramic Society of Japan 116 1349 100 - 104 2008年 [査読有り]
     
    The crystallographic orientation relationship between hydroxyapatite (HAp) nanocrystals and poly (acrylic acid) (PAA) graftpolymer-modified poly (ethylene terephthalate) (PET) substrate was studied using transmission electron microscopy (TEM). We observed the microstructure of fabricated rod-like HAp nanocrystals and the interface of HAp/PET composite where, the HAp nanocrystals are bonded onto PAA graftpolymer-modified PET substrate. The selected-area electron diffraction (SAED) pattern of interface of the HAp/PET composite indicated that some low index planes in HAp prism plane tended to be contact plane with the PET substrate surface. In particular, the [1120] plane was distinctly found as the contact plane with PET substrate. In this material, it has been reported that the carboxyl groups of PAA graft-polymer are ionically-bonded with Ca ions on surface of the HAp nanocrystal. It was suggested that the periodic ionic arrangements of the [1120] plane play an important role on the bonding between the HAp nanocrystals and the carboxyl groups of graft-polymer on the PET substrate.
  • Syuji Fujii; Masahiro Okada; Tsutomu Furuzono
    JOURNAL OF COLLOID AND INTERFACE SCIENCE 315 1 287 - 296 2007年11月 [査読有り]
     
    Hydroxyapatite (HAp) nanoparticles with spherical, rod-shaped or fiber-shaped morphologies were synthesized by wet chemical method in aqueous media. Scanning electron microscopy, dynamic light scattering, helium pycnometry, and aqueous electrophoresis techniques were used to characterize the nanoparticles in terms of their particle size and morphology, density and zeta potential, respectively. Stable "Pickering-type" emulsions were prepared using the HAp nanoparticles as a particulate emulsifier and methyl myristate as an oil phase above pH 7.7, but not below pH 6.1. These emulsions were characterized in terms of their emulsion type, mean droplet diameter and morphology using electrical conductivity, light diffraction and optical microscopy. Rapid demulsification could be induced by lowering the solution pH: addition of acid led to dissolution of the HAp nanoparticles attached on oil-water interface and the emulsion was destabilized. HAp nanoparticles precipitated by addition of base to the aqueous phase after demulsification and the HAp particles precipitated worked as an effective particulate emulsifier. This emulsification-demulsification cycle was reversible. Sintering of methyl myristate-in-water emulsion stabilized with the HAp nanoparticles led to a porous HAp material. (C) 2007 Elsevier Inc. All rights reserved.
  • M. Okada; T. Furuzono
    JOURNAL OF NANOPARTICLE RESEARCH 9 5 807 - 815 2007年10月 [査読有り]
     
    Sintering-free nanocrystals of calcined hydroxyapatite (HAp) having a rod-like morphology were fabricated by calcination at 800 degrees C for 1 h with an anti-sintering agent surrounding original HAp particles and the agent was subsequently removed after calcination. The original HAp particles having a rod-like morphology with a size ranging from 30 to 80 nm (short axis) and 300 to 500 nm (long axis) were prepared by wet chemical process, and poly(acrylic acid, calcium salt) (PAA-Ca) was used as the anti-sintering agent. In the case of calcination without additives, the mean size of HAp crystals dispersed in an ethanol medium increased by about 4 times and the specific surface area of the crystals exhibited a 25% decrease compared to those of the original HAp particles because of calcination-induced sintering among the crystals. On the other hand, the HAp crystals calcined with the anti-sintering agent, PAA-Ca, could be dispersed in an ethanol medium at the same size as the original particles, and they preserved the specific surface area after calcination. These results indicate that PAA-Ca and/or its thermally decomposed product, CaO, surrounded the HAp particles and protected them against calcination-induced sintering during calcination. The HAp crystals calcined with PAA-Ca showed high crystallinity, and no other calcium phosphate phases could be detected after washing with water.
  • Toshimitsu Tanaka; Motohiro Hirose; Noriko Kotobuki; Hajime Ohgushi; Tsutomu Furuzono; Junichi Sato
    Materials Science and Engineering C 27 4 817 - 823 2007年05月 [査読有り]
     
    A novel biomaterial that was composed of nano-scaled sintered hydroxyapatite (HAp) and silk fibroin (SF) was fabricated. We cultured rat marrow mesenchymal cells (MMCs) on this biomaterial (nano-HAp/SF sheet), on bare SF sheets, and on tissue culture polystyrene (TCPS) dishes as controls, then evaluated cell adhesion, proliferation, and differentiation of the MMCs. After 1 h of culture, a large number of viable cells were observed on the nano-HAp/SF sheets in comparison to the controls. In addition, after 3 h of culture, the morphology of the cells on the nano-HAp/SF sheets was quite different from that on the SF sheets. MMCs extrude their cytoplasmic processes to nano-HAp particles and are well attached to the sheets. After 14 days of culture, under osteogenic conditions, the alkaline phosphatase (ALP) activity and bone-specific osteocalcin secretion of the cells on nano-HAp/SF sheets were higher than were those on the controls. These results indicated that the surface of the nano-HAp/SF sheets is covered with appropriate HAp crystal for MMC adhesion/proliferation and that the sheets effectively support the osteogenic differentiation of MMCs. Therefore, the nano-HAp/SF sheet is an effective biomaterial that is applicable in bone reconstruction surgery. © 2006 Elsevier B.V. All rights reserved.
  • Masahiro Okada; Tsutomu Furuzono
    JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY 7 3 848 - 851 2007年03月 [査読有り]
     
    Nano-sized crystals of calcined hydroxyapatite (HAp) having spherical morphologies were fabricated by calcination at 800 degrees C for 1 h with an anti-sintering agent surrounding the original HAp particles and the agent was subsequently removed by washing after calcination. The original HAp particles were prepared by a modified emulsion system, and surrounded with poly(acrylic acid, calcium salt) (PAA-Ca) by utilizing a precipitation reaction between calcium hydroxide and poly(acrylic acid) adsorbed on the HAp particle surfaces in an aqueous medium. In the case of calcination without PAA-Ca, micron-sized particles consisting of sintered polycrystals were mainly observed by scanning electron microscopy, indicating the calcination-induced sintering among the crystals. On the other hand, most of the crystals calcined with the anti-sintering agent were observed as isolated particles, and the mean size of the HAp crystals was around 80 nm. This result indicates that PAA-Ca and its thermally decomposed product, CaO, surrounding the HAp crystals could protect them against calcination-induced sintering during calcination at 800 degrees C. The HAp crystals calcined with PAA-Ca showed high crystallinity, and no other calcium phosphate phases could be detected.
  • Tsuyoshi Kimura; Sayaka Iwai; Toshiyuki Moritan; Kwangwoo Nam; Shingo Mutsuo; Hidekazu Yoshizawa; Masahiro Okada; Tsutomu Furuzono; Tosihya Fujisato; Akio Kishida
    JOURNAL OF ARTIFICIAL ORGANS 10 2 104 - 108 2007年 [査読有り]
     
    Poly(vinyl alcohol) (PVA) hydrogels interacting with DNA mediated by hydrogen bonds (PVA/DNA hydrogel) were developed using ultra-high pressure (UHP) technology. The goal was to create a new method of gene delivery by controlled release of DNA. Mixed solutions of DNA and PVA at various concentrations were pressurized at 10000 atmospheres at 37 degrees C for 10min. PVA/DNA hydrogels with good formability were produced at PVA concentrations of more than 5% w/v. The presence of DNA in the obtained hydrogels was confirmed by spectroscopic analysis and nucleic acid dye staining. DNA release from the hydrogels was investigated using PVA/DNA hydrogel samples of 5% and 10% w/v formed by UHP treatment or by conventional freeze-thaw methods. The DNA release curves from both types of samples showed a rapid phase in the initial 15 h followed by a sustained release phase. However, there was a difference in the amount of DNA released. Less DNA was released by the pressurized hydrogels than by the freeze-thaw hydrogels. Also, the cumulative amount of DNA released decreased as the PVA content in the hydrogels increased. These results indicate that DNA release from the hydrogels can be modulated by changing the preparation method and the PVA content. Furthermore, it was demonstrated that DNA release could be controlled by varying the amount and duration of pressurizing used to form the hydrogels. Intact fractions of plasmid DNA released from the hydrogels were separated by agarose gel electrophoretic analysis. These results suggest that, using controlled release, DNA from PVA/DNA hydrogels formed by UHP treatment can be transfected into cells.
  • Fabrication of high-dispersibility nanocrystals of calcined hydroxyapatite
    M. Okada; T. Furuzono
    J. Mater. Sci 41 6134 - 6137 2006年09月 [査読有り]
  • Nano-scaled hydroxyapatite/silk fibroin composites as mesenchymal cell culture scaffolds
    M. Hirose; K. Hamada; T. Tanaka; N. Kotobuki; H. Ohgusi; S. Yasuda; T. Furuzono
    Key Engineering Materials 309-311 923 - 926 2006年05月
  • T Furuzono; M Masuda; M Okada; S Yasuda; H Kadono; R Tanaka; K Miyatake
    ASAIO JOURNAL 52 3 315 - 320 2006年05月 [査読有り]
     
    Nano-scaled sintered hydroxyapatite (HAp) crystals were covalently linked onto a poly(ethylene terephthalate) (PET) fabric substrate chemically modified by graft polymerization with gamma-methacryloxypropyl triethoxysilane (MPTS) for development of an artificial blood vessel. The weight gain of graft polymerization with poly(MPTS) on PET in benzyl alcohol containing H2O2 as an initiator increased as increasing the reaction time and finally reached a plateau value of about 3.5 wt%. The surface characterization of surface modification with poly(MPTS)-grafting was conducted by x-ray photoelectron spectroscopy. HAp nanocrystals of approximately 50 nm in diameter, monodispersed in pure ethanol, were coupled with alkoxysilyl groups of the poly(MPTS)-grafted PET substrate. The HAp nanocrystals were uniformly and strongly coated on the surface of the PET fabrics, although HAp particles adsorbed physically on the original PET without poly(MPTS) grafting were almost removed by ultrasonic wave treatment. More human umbilical vein endothelial cells adhered to the HAp/PET composite fabric compared with original PET after only 4 hours of initial incubation, and the same was observed on the collagen-coated PET. The coating of sintered HAp nanocrystals imparted bioactivity to the polyester substrate, which is a widely used biomedical polymer, without a coating of adhesion proteins derived from animals, such as collagen or gelatin. A prototype of an artificial blood vessel was finally fabricated by use of HAp/PET composite.
  • 柔軟な絹フィブロインフィルムの開発
    河原 豊; 古川敬子; 山本岳志; 益田美和; 古薗 勉
    日本シルク学会誌 15 3 - 6 2006年
  • M Okada; S Yasuda; T Kimura; M Iwasaki; S Ito; A Kishida; T Furuzono
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 76A 1 95 - 101 2006年01月 [査読有り]
     
    A composite consisting of titanium dioxide (TiO2) particle, the surface of which was modified with amino groups, and a silicone substrate through covalent bonding at their interface was developed, and antibacterial and cell adhesion activities of the composite were evaluated. The density of the amino groups on the TiO2 particle surface was controlled by the reaction time of the modification reaction. The degradation rate of CH3CHO in the presence of the TiO2 particles under UV irradiation decreased with an increase in the amino group density on the TiO2 surface. On the other hand, the number of L929 cells adhering on the TiO2/silicone composite increased with an increase in the amino group density. From the above two results, the optimum density of amino groups for both photoreactivity and cell adhesiveness was estimated to be 2.0-4.0 molecules/ run 2. The optimum amino group-modified TiO2/silicone composite sheet (amino group density, 3.0 molecules/nm(2)) showed an effective antibacterial activity for Escherichia coli bacteria under UV irradiation. (c) 2005 Wiley Periodicals, Inc.
  • T. Furuzono; D. Walsh; S. Yasuda; K. Sato; J. Tanaka; A. Kishida
    Journal of Materials Science 40 9-10 2595 - 2597 2005年05月 [査読有り]
     
    A micrometer-sized and plated ceramic consisting of β-tricalcium phosphate (TCP) and a calcium-deficient apatite was developed to increase interface interaction between a ceramic and substrate, and to prevent aggregation. The prepared ceramic was characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electron microscopy (TEM). The content of the hydroxyapatite (HAp) phase in the plated calcium phosphate could be controlled by calcination time at 800 °C. The plates of β-TCP containing HAp are expected to be more suitable for coating of a polymer surface due to the larger surface area of adhesion to the substrate.
  • T Furuzono; S Yasuda; J Tanaka; A Kishida
    JOURNAL OF MATERIALS SCIENCE 40 9-10 2627 - 2629 2005年05月 [査読有り]
  • A Korematsu; T Furuzono; A Kishida
    MACROMOLECULAR MATERIALS AND ENGINEERING 290 1 66 - 71 2005年01月 [査読有り]
     
    Novel block copolymers containing aromatic polyamide (aramid) and fluoroethylene segments were synthesized by a two-step solution polycondensation. This synthetic method could control the chain-length of aramid segments and these copolymers could have high structural regularity. The number-average molecular weight ((M) over bar (n)) of one of these polymers is over 2.0 x 10(4). Incorporation fluoro-ethylene segments improves the solubility of the resulting polymer compared with conventional armaids.
  • A Korematsu; T Furuzono; S Yasuda; J Tanaka; A Kishida
    JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE 16 1 67 - 71 2005年01月 [査読有り]
     
    A novel composite coupling between nano-scaled hydroxyapatite (HAp) particles and poly[ 4-methacryloyloxyethyl trimellitate anhydride (4-META)]-grafted silk fibroin (SF) through ionic interaction was synthesized. The weight gain of poly(4-META) by graft-polymerization increased with increasing the reaction time, eventually reaching a plateau value of about 20 wt%. The HAp nano-particles were adsorbed equally and dispersively on the treated SF fiber surface. The HAp content in the composite was 4.554 wt% +/- 0.098 (n = 4), confirmed by thermogravimetry (TG). This synthetic system requires no heat to connect HAp to SF and is useful when applying to non-heat-resistant polymers. The L-929 cell-adhesion test shows that the HAp/SF composite improves bioactivity compared to the original SF (C) 2005 Springer Science + Business Media, Inc.
  • Novel PVA-DNA Nanoparticles Prepared by Ultra High Pressure Technology for Gene Delivery
    T.Kimura; A.Okuno; K.Miyazaki; T.Furuzono; Y.Ohya; T.Ouchi; S Mutsuo; H.Yoshizawa; Y.Kitamura; T.Fujisato; A.Kishida
    Material Science&Engineering C 24(6-8), 797-801 2004年12月
  • Tsutomu Furuzono; Shoji Yasuda; Tsuyoshi Kimura; Singo Kyotani; Junzo Tanaka; Akio Kishida
    Journal of Artificial Organs 7 3 137 - 144 2004年09月 [査読有り]
     
    Nano-scaled sintered hydroxyapatite (HAp) particles with an a-axis length of 87 ± 23 nm, a c-axis length of 236 ± 81 nm, and a mean aspect ratio (cla) of 2.72 were covalently linked onto a silk fibroin (SF) substrate chemically modified by graft polymerization with γ-methacryloxypropyl trimethoxysilane (MPTS). Graft polymerization with poly(MPTS) on SF was conducted by free-radical initiation in a water solvent with pentaethylene glycol dodecyl ether as a nonionic surfactant. The alkoxysilyl groups of the graft polymers avoided hydrolysis and maintained their activity in coupling with the hydroxyl groups on the HAp surface despite the use of water as the reaction solvent. The weight gain of poly(MPTS) on SF increased with increasing the reaction time, eventually reaching a plateau value of about 15 wt% after 50 min of reaction time. After HAp covalent coating, the particles separated or aggregated into several crystals, as shown by scanning electron microscopic observation. L929 fibroblast cells adhered more plentifully on HAp-coated SF compared to untreated SF and hydrolyzed poly(MPTS)-grafted SF during 24 h or 48 h of incubation. The cells adhered only on the HAp surface but not at all on the dehydrated grafted surface of SF without HAp. A button-shaped prototype for a percutaneous device was manufactured by transplantation of HAp-coated SF fibers of about 100 μin length onto silicone moldings using an adhesive, and the device showed good cell adhesiveness.
  • A Korematsu; T Furuzono; S Yasuda; J Tanaka; A Kishida
    JOURNAL OF MATERIALS SCIENCE 39 9 3221 - 3225 2004年05月 [査読有り]
  • T Furuzono; A Kishida; J Tanaka
    JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE 15 1 19 - 23 2004年01月 [査読有り]
     
    The inorganic-organic composite consisting of a nano-scaled hydroxyapatite (HAp) and silk fibroin (SF) fibers was prepared through convalent linkage to develop a novel biomaterial for a soft-tissue-compatible material. The preparation of the composite was conducted through the three-step procedure consisting of chemical modification using 2-methacryloxyethyl isocyanate (MOI) monomer to introduce vinyl groups on SF, poly(gamma-mehtacryloxypropyl trimethoxysilane) (MPTS) graft-polymerization of SF, and coupling process between the surface of polyMPTS-grafted SF and HAp nano-particles. The amount of the graft-polymerization of polyMPTS through vinyl groups was well controlled by the reaction time. The nano-crystals were subsequently coated on the grafted fibers by heating at 120degreesC for 2 h in a vacuum. The crystalline structure of the SF substrate did not change in the procedure. In the SEM observation of the composite surface, it was found that the bonded nano-crystals were separated and partially aggregated with several crystals attached on the SF fiber surface. The HAp particles adhered more strongly on the SF surface with separation or aggregation of several crystals than on the surface of the original SF after ultrasonic treatment. (C) 2004 Kluwer Academic Publishers.
  • T. Furuzono; M. Iwasaki; S. Yasuda; A. Korematsu; T. Yoshioka; S. Ito; A. Kishida
    Journal of Materials Science Letters 22 24 1737 - 1740 2003年12月 [査読有り]
     
    A novel composite consisting of TiO2 particles and a polymer substrate by covalent linkage was developed. The photoreactivity of the amino-group-modified TiO2 remained, although the reactivity was lower than that of the original TiO2. Severe control of the synthetic reaction condition in the amino-group donation to TiO2 made it possible to increase the photoreactivity of the modified TiO2.
  • Atsushi Matsuda; Tsutomu Furuzono; Dominic Walsh; Akio Kishida; Junzo Tanaka
    Journal of Materials Science: Materials in Medicine 14 11 973 - 978 2003年11月 [査読有り]
     
    Porous hydroxyapatite (Hap) blocks were sintered at several temperatures and methyl methacrylate (MMA) grafted onto the surface in a 2-step heterogeneous system as a model example for surface modification. First, sintered porous Hap was modified with 2-methacryloyloxyethylene isocyanate (MOI) monomer in anhydrous dimethyl sulfoxide using di-n-butyltin (IV) dilaurate as a catalyst and hydroquinone as an inhibitor. Amount of the introduction of MOI monomer on porous Hap was 1.62 wt% at sintered temperature 800°C, 0.68 wt% at it of 1000°C, and 0.59 wt% at it of 1200°C. Scanning electron microscopy (SEM) showed that porous Hap pore size and shape before and after MOI treatment were unchanged. Second, graft polymerization with MMA through the vinyl bond on porous Hap was conducted using α,αprime -azobis isobutyronitrile (AIBN) as an initiator. Amount of Grafted PMMA on the MOI modified porous Hap was 2.84 wt% at sintered temperature of 800αC, 6.97 wt% at it of 1000αC, and 6.27 wt% at it of 1200αC. MOI-modified and PMMA-grafted porous Hap were characterized using Fourier transform infrared (FT-IR) spectroscopy. The compressive strength of sintered porous Hap with grafted PMMA increased about 2.7-6.7 times compared to intact porous Hap. This 2-step surface modification on porous Hap is widely applicable to graft polymerization with vinyl polymer and conjugation with a protein or an oligopeptide, such as growth factor or an adhesion molecule, to improve Hap mechanical properties and functionality. © 2003 Kluwer Acadamic Publishers.
  • A Korematsu; T Furuzono; A Kishida
    JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY 41 18 2840 - 2845 2003年09月 [査読有り]
  • Tsutomu Furuzono; Pao-Li Wang; Arata Korematsu; Kozo Miyazaki; Mari Oido-Mori; Yusuke Kowashi; Kiyoshi Ohura; Junzo Tanaka; Akio Kishida
    Journal of Biomedical Materials Research - Part B Applied Biomaterials 65 2 217 - 226 2003年05月 [査読有り]
     
    A composite (HA/silicone) of hydroxyapatite (HA) microparticles with an average diameter of 2.0 μm covalently linked to a silicone substrate has been developed, and its physical and biological properties as a percutaneous soft-tissue-compatible material have been evaluated. In tensile property measurement, samples of HA/silicone and the original silicone were similar in tensile strength, ca. 7.8 MPa, and elongation at break, ca. 570%. It was found that chemical surface modification with HA particles presented no mechanical disadvantage. In an adhesive-tape peeling test, scanning electron microscopic (SEM) observation showed that HA particles coupled directly to the substrate were not removed. HA particles may bond strongly with the substrate. In human periodontal ligament fibroblast attachment and proliferation experiments, the number of cells attached to HA/silicone was 14 times greater than that attached to the original silicone after 24 h of incubation. The value on HA/silicone was ca. 80% versus that on a tissue-culture plastic used as a positive control. After 72 h of incubation, the number of cells grown on HA/silicone increased to the level of the positive control. In observation of fluorescence microscopy stained by Hoechst 33342, cells appeared to tightly adhere to HA particles coupled to the silicone sheet due to intact nuclear morphology. Observation of cells by fluorescence dye with rhodamin phalloidin showed an extensive F-actin cytoskeleton on HA/silicone. In a 4-week animal implant test, force required to pull out the HA/silicone sheet was 15 times that of the original silicone. HA-particle coating on silicone with covalent linkage gave the inert surface bioactivity. The HA composite thus effectively prevents germ infection percutaneously. © 2003 Wiley Periodicals, Inc.
  • Kensaku Sonoda; Tsutomu Furuzono; Dominic Walsh; Kimiyasu Sato; Junzo Tanaka
    Solid State Ionics 151 1-4 321 - 327 2002年11月 [査読有り]
     
    The effect of an emulsion medium on the morphology and size of hydroxyapatite (HAp) nanoparticles was investigated. The HAp particles prepared in a pentaethyleneglycol dodecylether emulsion were smaller in size and in aspect ratio than those prepared from a non-emulsion. Morphological difference was also observed between the products prepared in the two systems. The edges of the HAp particles derived from the emulsion system were curved and rounded while those in the non-emulsion system were straight and truncated. These differences, deriving from the reaction media employed, indicated that a template effect of the emulsion can be utilized for controlling the size and habit of HAp nanoparticles. © 2002 Elsevier Science B.V. All rights reserved.
  • Dominic Walsh; Tsutomu Furuzono; Junzo Tanaka
    Biomaterials 22 11 1205 - 1212 2001年06月 [査読有り]
     
    Biodegradable and biostable composite foams were formed from porous apatite cement infiltrated with ε-caprolactone (CL) or methylmethacrylate (MMA) using a high over vacuum. For CL composites in situ polymerization was induced using trace water as an initiator and heating at 120°C for up to 10 days or at 80°C for 60 days. MMA composites were polymerized using AIBN initiator at 70°C for 8h. CL preparations gave composites with a polycaprolactone (PCL) number average of molecular weight (Mn) up to the maximum of 7.1×103g/mol after 10 days and 16.8×103g/mol after 60 days. The PCL and PMMA contents were close to 50 and 40wt%, respectively, polymer was present as a thin coating on the apatite crystal plates and was evenly distributed throughout the samples. Re-evacuation of apatite saturated with monomer during preparation ensured that the upwards of 200nm microchannels within the apatite cement were largely free of polymer, and the overall macroporous structure of the apatite foams was partly retained. Maximum compressive strengths increased from 9MPa to 37 and 64MPa for PCL and PMMA composites, respectively. The water drop contact angle of the PCL composite was 64°, and therefore suitable for cell attachment. PMMA composite surfaces were more hydrophobic. Composites were subjected to corona discharge to induce suitable moderate hydrophilicity at the surface. Copyright © 2001 Elsevier Science Ltd.
  • T. Furuzono; D. Walsh; K. Sato; K. Sonoda; J. Tanaka
    Journal of Materials Science Letters 20 2 111 - 114 2001年01月 [査読有り]
  • Tsutomu Furuzono; Kensaku Sonoda; Junzo Tanaka
    Journal of Biomedical Materials Research 56 1 9 - 16 2001年 [査読有り]
     
    A novel composite consisting of hydroxyapatite (HAp) microparticles covalently coupled onto a silicone sheet was developed. Initially, an acrylic acid (AAc) -grafted silicone sheet with a 16.7 μg/cm2 surface graft density was prepared by corona-discharge treatment. The surface of sintered, spherical, carbonated HAp particles with an average diameter of 2.0 μm was subsequently modified with amino groups. The amino group surface density of the HAp particles was calculated to be approximately one amino molecule per 1.0 nm2 of particle surface area. These samples were characterized with Fourier transform infrared spectrometry and X-ray photoelectron spectroscopy. After the formation of ammonium ionic bonds between both samples under aqueous conditions, they were reacted at 180°C for 6 h in vacuo to form covalent bonds through a solid-phase condensation. The HAp particles were coupled to the AAc-grafted silicone surface by a covalent linkage. Further improvements in the adhesive and bioactive properties of the HAp-coated silicone material are expected. © 2001 John Wiley & Sons, Inc.
  • A Kishida; T Kanda; T Furuzono; Maruyama, I; M Akashi
    JOURNAL OF APPLIED POLYMER SCIENCE 78 12 2198 - 2205 2000年12月 [査読有り]
     
    A blending technique was studied in order to widen the applications of aramid-silicone multiblock copolymer (PAS). A PAS/aramid blend film was prepared and the characterization of the surfaces was investigated. The two-phase nature of poly(dimethylsiloxane) (PDMS) and the aromatic polyamide (aramid) multiblock copolymer (PAS) were clarified in part by evaluating the surface enrichment in PAS/aramid blend films. There were no significant differences among the PASs as additives; however, the PASs were able to alter the aramid surface to that of silicone, even though they were used at low concentration. The atomic force microscopy observation suggested that the mobility of the silicone segment that existed on the surface was restricted by the associated aramid segments. (C) 2000 John & Wiley & Sons, Inc.
  • Toshiro Uchida; Tsutomu Furuzono; Kazuhiko Ishihara; Nobuo Nakabavashi; Mitsuru Akashi
    Journal of Polymer Science, Part A: Polymer Chemistry 38 17 3052 - 3058 2000年09月 [査読有り]
     
    Polystyrene core nanosphere particles possessing 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers on the corona were prepared by the free radical polymerization of hydrophilic polyMPC macromonomer and hydrophobic styrene with AIBN as a radical initiator in ethanol as a polar solvent. The morphology of the nanoshperes was observed by transmission electron micrograph (TEM). The nanospheres were spherical in form and have a narrow size distribution. Their sizes could be controlled by varying the molecular weight of the macromonomer and the amount of it in feed. Electron spectroscopy for chemical analysis (ESCA) of the nanoshpere surfaces suggested that ployMPC chains were located favorably on the surface of the nanospheres. The nanospheres having the polyMPC chains on their surfaces can be significant and useful materials in technological and medical fields.
  • T Furuzono; T Taguchi; A Kishida; M Akashi; Y Tamada
    JOURNAL OF BIOMEDICAL MATERIALS RESEARCH 50 3 344 - 352 2000年06月 [査読有り]
     
    Apatite-deposited silk fabric composite materials were developed using a new alternate soaking process. The characteristics of deposited apatite were studied using scanning electron microscopy (SEM), X-ray diffaction (XRD), Fourier transform infrared spectrophotometry (FTIR), and X-ray photoelectron spectroscopy (XPS). Apatite weight increased with alternating soaking in a calcium solution [200 mM aqueous calcium chloride solution buffered with tris-(hydroxymethyl) aminomethane and HCl (pH 7.4)] and a phosphate solution (120 mM aqueous disodium hydrogenphosphate) changed every hour. SEM showed that apatite deposited after 21 or more repeated soakings was over 20 mu m thick. XRD showed that with alternate soakings, the apatite crystals deposited on silk fabric elongated along the axis. FTIR and XPS indicated the existence of carbonate, HPO42-, and Na+ ions in addition to constituent ions of hydroxyapatite. A loss of HPO42- and Na+ ions in the deposit upon further soaking might be associated with an increasing apatite crystallinity. Apatite deposited on silk by the alternate soaking process was a deficient apatite containing carbonate, HPO42- and Na+ ions as in a natural bone tissue. Thus, this apatite-silk composite material might be potentially bioactive. (C) 2000 John Wiley & Sons, Inc.
  • T. Furuzono; K. Ishihara; N. Nakabayashi; Y. Tamada
    Biomaterials 21 4 327 - 333 2000年02月 [査読有り]
     
    2-Methacryloyloxyethyl phosphorylcholine (MPC) was grafted onto silk fabric in a two-step heterogeneous system through the vinyl bonds of 2-methacryloyloxyethyl isocyanate (MOI) modified on the fabric. First, habutae silk fabric was modified with the MOI monomer in anhydrous dimethyl sulfoxide using di-n-butyltin (IV) dilaurate and hydroquinone at 35°C. The saturated weight gain of modified MOI monomer on the fabric was 7.3wt% versus the original silk. Second, graft polymerization with MPC onto the MOI modified silk was conducted using 2,2'-azo bis[2-(2-imidazolin-2-yl)propane dihydrochloride] (VA-044) as an azo polymerization initiator. The weight of the grafted MPC eventually gained was about 26.0wt%. The MOI-modified and MPC-grafted silk fabrics were analyzed by Fourier transform infrared (FT-IR) spectroscopy. To confirm the improved biocompatibility of the silk fabric, platelet adhesion was preliminarily tested measuring lactate dehydrogenase. The number of platelets adhering to polyMPC-grafted silk fabric decreased by about one tenth compared to original and MOI-modified silk after 60min of contact with human platelet-rich plasma (1.0x106plateletscm-2). Copyright (C) 2000 Elsevier Science B.V.
  • Nucleation of Hydrixyapatite on an Inert Polymer Surface by Covalent Linkage
    T. Furuzono; K. Sonoda; J. Tanaka
    Transactions of the Mater. Res. Society of Japan, 25 4 915 - 918 2000年
  • Satoshi Sakoda; Hiroshi Shin; Katsuyo Yamaji; Ikuko Takasaki; Tsutomu Furuzono; Akio Kishida; Mitsuru Akashi; Toshikazu Kubo; Eiichi Nagaoka; Ikuro Maruyama; Isao Kitajima
    Pathophysiology 6 1 63 - 69 1999年04月 [査読有り]
     
    Mechanical stimulation of osteoblasts has been shown to induce changes in phenotype at the cellular level. The cellular changes resulting from the mechanical stretching of human osteoblast-like cells (MG-63) cultured on flexible silicone-coated films were investigated. With a quantitative competitive polymerase chain reaction (PCR) methods, whether mechanical stimuli induce osteogenic gene expressions and cytokine productions in the mechanical stretching of human osteoblast-like cells (MG-63) cells was examined. Expressions of protooncogene (c-fos), bone morphogenic proteins (BMP-2 and BMP-4), and the BMPs' receptor, i.e. activin receptor-like kinase- 3 (ALK-3), increased after stretching, c-fos, BMP-2, and BMP-4 mRNA levels reached their peaks 0.5 h after stretching began, while ALK-3 mRNA reached a maximum level 2 h after stretching started. When the culture medium was assayed for cytokine activities, macrophage-colony stimulating factor (M- CSF) was found at the maximum concentration after 4 h of stretching. These results suggest that mechanical stimuli affect the expressions of BMPs and their receptors, and the continuous M-CSF expression might induce differentiation of osteoblasts.
  • Tsutomu Furuzono; Kazuhiko Ishihara; Nobuo Nakabayashi; Yasushi Tamada
    Journal of Applied Polymer Science 73 12 2541 - 2544 1999年 [査読有り]
     
    In order to improve the biocompatibility of silk fabric, 2-methacryloyloxyethyl phosphorylcholine (MPC) was grafted onto silk fabric by free radical initiation. Platelet adhesion was preliminarily tested. By measuring biocompatibility, the effect of grafted MPC on silk fabric was confirmed.
  • Y Tamada; T Furuzono; T Taguchi; A Kishida; M Akashi
    JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 10 7 787 - 793 1999年 [査読有り]
     
    Silk fabric was modified with polymethacryloyloxyethylphosphate (pMOEP) by graft copolymerization. Ca-adsorption onto pMOEP-grafted silk fabric was significantly enhanced compared to that onto original silk fabric. SEM observation indicated that some crystallites were deposited on the pMOEP-grafted silk fabric after 1 week of immersion in simulated body fluid, whereas no change occurred on the surface of the original silk fabric. X-ray diffraction showed that this crystallite contained hydroxyapatite. These results indicate that pMOEP-grafted silk fabric induce hydroxyapatite formation more effectively than the original silk fabric.
  • K. Senshu; T. Furuzono; N. Koshizaki; S. Yamashita; T. Matsumoto; A. Kishida; M. Akashi
    Macromolecules 30 15 4421 - 4428 1997年06月
  • Novel functional polymers: Poly(dimethylsiloxane)-polyamide multiblock copolymer VII. Oxygen permeability of aramid-silicone resin membranes in gas-membrane-liquid system
    T. Matsumoto; T. Uchida; A. Kishida; T. Furuzono; I. Maruyama; M. Akashi
    J. Appl. Polym. Sci. 64 6 1153 - 1159 1997年
  • Tsutomu Furuzono; Kazuhisa Senshu; Akio Kishida; Takeo Matsumoto; Mitsuru Akashi
    Polymer Journal 29 2 201 - 203 1997年 [査読有り]
  • Takeo Matsumoto; Yasumi Koinuma; Kazunori Waki; Akio Kishida; Tsutomu Furuzono; Ikuro Maruyama; Mitsuru Akashi
    Journal of Applied Polymer Science 59 7 1067 - 1071 1996年02月 [査読有り]
     
    Poly(dimethylsiloxane) (PDMS) and aromatic polyamide (aramid) multiblock copolymers (PASs) ranging from 26 wt % to 75 wt % in PDMS content were prepared and cast into transparent, ductile, and elastomeric films from N,N′-dimethylacetamide solutions. The gas permeation properties and dynamic thermomechanical properties of the PAS films were investigated. It was found that the PASs containing < 75 wt % of PDMS had two-phase morphologies due to the great difference between the solubility parameters of the two components, in spite of the relatively low molecular weight of each segment. PASs containing ≥ 35 wt % of PDMS showed the PDMS continuous phase and interfacial mixing occurred clearly between the two phases at the higher PDMS contents. PAS containing ≥ 53 wt % of PDMS showed high enough gas permeability compared with conventional silicone rubbers. The gas permeation properties can be well predicted by the PDMS contribution to the continuous phase rather than by the modulus behaviors alone. © 1996 John Wiley & Sons, Inc.
  • T Furuzono; K Seki; A Kishida; TA Ohshige; K Waki; Maruyama, I; M Akashi
    JOURNAL OF APPLIED POLYMER SCIENCE 59 7 1059 - 1065 1996年02月 [査読有り]
     
    Disiloxane-aromatic polyamide (aramid) multiblock copolymers (2SiPASs) were synthesized using 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane (BATS) as an analog of aramid-silicone resin consisting of aromatic polyamide and poly(dimethylsiloxane) (PDMS). 2SiPASs afford a transparent and toughened plastic film. The surface properties of 2SiPAS were investigated by X-ray photoelectron spectroscopy (xps) and static contact angle measurement. The results of surface analysis suggested that BATS content of the 2SiPAS surface increased with increasing BATS content in bulk. The interaction between the platelets and the 2SiPAS surface was found to be very weak when the BATS content reached 26 wt % in bulk. (C) 1996 John Wiley & Sons, Inc.
  • Tsutomu Furuzono; Akio Kishida; Masakazu Yanagi; Takeo Matsumoto; Takashi Kanda; Takao Nakamura; Takashi Aiko; Ikuro Maruyama; Mitsuru Akashi
    Journal of Biomaterials Science, Polymer Edition 7 10 871 - 880 1996年01月 [査読有り]
     
    Multiblock copolymers consisting of aromatic polyamide(aramid) and poly(dimethylsiloxane) (PDMS) aramid-silicone resins (PASs) were synthesized by low temperature solution polycondensation, and PAS films were prepared by casting from an N, N'-dimethylacetamide solution. In this study, we investigated bovine serum albumin (BSA) adsorption, L929 cell adhesion, and tissue reaction on the surface of PAS in order to clarify the interaction between PAS and biomolecules. It was found that the amount of adsorbed biomolecules on PAS was extremely low in contrast with those on aramid and nylon films, and it was comparable to SILASTIC® 500-1 film. This suppression of adsorption of biomolecules onto PAS seemed to be due to the low surface free energy of the outermost surface of PAS, where PDMS block was condensed. © VSP 1996.
  • 非放射性RT-PCR-SSCP法による異常インスリンレセプターの遺伝子診断
    古薗 勉; 中島利博; 北島勲; 明石満; 鎌田哲郎; 瀬戸山史郎; 丸山征郎
    臨床病理 42 600 - 604 1994年
  • Akio Kishida; Tsutomu Furuzono; Taka‐aki Ohshige; Ikuro Maruyama; Takeo Matsumoto; Haruhiko Itoh; Mikio Murakami; Mitsuru Akashi
    Die Angewandte Makromolekulare Chemie 220 1 89 - 97 1994年 [査読有り]
     
    Ultrathin films of poly(dimethylsiloxane)‐polyamide copolymers (PAS) with different silicone contents were prepared by the methods of water casting and spin coating. The surface properties of the films were investigated in detail using contact angle measurements and X‐ray photoelectron spectroscopy (XPS). The water‐cast films were thin enough to be applicable as laminate films for an artificial lung or an air‐separator for oxygen‐enrichted air. Uniform and ultrathin films were obtained by the spin coating method. XPS and contact angle measurements suggested that poly(dimethylsiloxane) segments were condensed at the outermost surface of spin‐coated PAS films. XPS measurements also revealed that the surface properties of PAS were affected by the molding method, especially the solvent evaporation conditions. © 1994 Hüthig & Wepf Verlag, Zug
  • Tsutomu Furuzono; Eiji Yashima; Akio Kishida; Ikuro Maruyama; Takeo Matsumoto; Mitsuru Akashi
    Journal of Biomaterials Science, Polymer Edition 5 1-2 89 - 98 1994年01月 [査読有り]
     
    Aramid-silicone resins (PASs) consisting of aromatic polyamide (aramid) and poly(dimethyl- siloxane) (PDMS) segments were synthesized by low temperature solution polycondensation. For the evaluation of blood compatibility in vitro, two kinds of experiments were carried out. One was the thromboxane B2(TXB2) release test from platelets attaching to PAS and Biomer®. The other was the observation of the platelet adhesion on the surfaces of PAS by scanning electron microscopy (SEM). The results indicated that PAS was bio-inert in vitro. The surface chemical composition of PAS films was investigated by means of electron probe micro analysis (EPMA), X-ray photoelectron spectroscopy (XPS), and dynamic contact angle measurements. The relationship between blood compatibility and surface composition of PAS is discussed. © Taylor & Francis Ltd.
  • 角 明夫; 古薗 勉; 林 満
    日本作物九州支部会報 51 51 1 - 5 日本作物学会 1984年 
    サトウキビ品種NCo310とNi1間の耐早性の差異を定量的に把握することを目的にして,重量法により9段階の土壌水分処理を行い草丈,仮茎長および葉位と土壌水分問の関係について調査した。その結果の概要は次のとおりである。1.草丈,仮茎長および葉位と土壌水分問の関係は測定した土壌水分の範囲内において,いずれも双曲線関係を示す次式を摘用することによって近似的に定量化できることがわかった。

書籍

  • ヴィジュアルでわかるバイオマテリアル（改訂第4版）
    古薗 勉、岡田正弘 (担当:共編者(共編著者)範囲:)株式会社Gakken 2023年03月 ISBN: 9784055200400
  • 臨床工学技士標準テキスト 第4版
    古薗 勉 (担当:分担執筆範囲:生体物性材料工学―医用材料)金原出版 2022年03月
  • 在宅血液透析管理マニュアル（改訂版）
    (担当:その他範囲:)日本透析医会 2020年08月
  • MEの基礎知識と安全管理（改訂第7版）
    (担当:編者(編著者)範囲:ME機器の滅菌・消毒/MEに必要な医用材料)南江堂 2020年04月
  • 腹膜透析ガイドライン2019
    日本透析医学会 2019年11月
  • 臨床工学技士標準テキスト 第3版増補
    (担当:分担執筆範囲:生体材料工学)金原出版 2019年01月
  • ヴィジュアルでわかるバイオマテリアル（改訂第3版）
    古薗勉; 岡田正弘 (担当:共編者(共編著者)範囲:)学研メディカル秀潤社 2018年10月
  • "思う”ことで変えられる
    古薗勉 (担当:単著範囲:)はる書房 2017年07月
  • 臨床工学技士標準テキスト 第3版
    古薗 勉 (担当:分担執筆範囲:生体材料工学)金原出版 2016年12月
  • 専門研修トレーニング問題解説集 第2版
    古薗勉 (担当:分担執筆範囲:血液浄化に関連した機器，薬剤，検査)(社)日本透析医学会 専門医制度委員会 2015年08月
  • MEの基礎知識と安全管理 改訂第6版
    古薗 勉; 峰島三千男 (担当:分担執筆範囲:第4章 MEに必要な医用材料)南江堂 2014年04月
  • 第１種ME技術実力検定試験テキスト
    竹澤真吾; 古薗 勉; 峰島三千男 (担当:分担執筆範囲:第1部第6章 医用材料工学)(社)日本生体医工学会ME技術教育委員会（監）、第1種ME技術実力検定試験テキスト編集委員会（編） 2014年03月
  • 臨床工学技士標準テキスト 第2版増補
    古薗 勉 (担当:分担執筆範囲:ⅩⅣ.生体材料工学)金原出版 2014年02月
  • 体内埋め込み医療材料の開発とその理想的な性能・デザインの要件
    古薗勉 (担当:分担執筆範囲:臨床で求められる新しい複合ポリマー材料)技術情報協会 2013年10月
  • Biomimetics: Advancing Nanobiomaterials and Tissue Engineering
    S. Fujii; M. Okada; T. Furuzono (担当:分担執筆範囲:Hydroxyapatite-biodegradable polymer nanocomposite microspheres toward injectable cell scaffold)John Wiley & Sons, Inc. 2013年
  • （増補新訂版）人工臓器は、いま
    古薗勉 (担当:分担執筆範囲:人工腎臓)はる書房 2012年12月
  • 専門医試験問題解説集（改訂第七版）
    古薗勉 (担当:分担執筆範囲:透析膜素材と生体適合性/透析回路・滅菌法)医学図書出版 2012年05月
  • 臨床工学技士標準テキスト 第2版
    古薗勉 (担当:分担執筆範囲:ⅩⅣ. 生体材料工学)金原出版 2012年02月
  • 新版 ヴィジュアルでわかるバイオマテリアル
    古薗勉; 岡田正弘 (担当:共編者(共編著者)範囲:)学研メディカル秀潤社 2011年12月
  • 共創・協奏—産学連携成功のキーワード—
    古薗勉 (担当:分担執筆範囲:抗感染性カテーテルの開発と私)アドスリー 2011年07月
  • 新材料・新素材シリーズ コアシェル微粒子の設計・合成技術・応用の展開
    藤井秀司; 岡田正弘; 古薗 勉; 福本真也 (担当:分担執筆範囲:ピッカリングエマルション法によるコアシェル粒子の合成)シーエムシー出版 2010年07月
  • BOTTOM-UP NANOFABRICATION: Supramolecules, Self-Assemblies, and Organized Films
    K. Ariga and H. S. Nalwa (Eds) (担当:分担執筆範囲:Nanofabrication of Inroganic-Organic Composites by Chemical Bonding for Medical Devices)American Scientific Publishers 2009年 ISBN: 1588830799
  • 環境調和型新材料シリーズ 生体材料
    古薗 勉 (担当:分担執筆範囲:抗感染性カテーテルをつくる—高分子複合材料)日刊工業新聞社 2008年10月
  • 再生医療技術の最前線
    古薗 勉; 小粥康充; 岡田正弘 (担当:分担執筆範囲:第1章スキャホールド, 3.コンポジット材料)シーエムシー出版 2007年06月
  • 機能材料
    古薗 勉; 岡田正弘; 小粥康充 (担当:分担執筆範囲:ナノアパタイト単結晶体コーティング)シーエムシー出版 2007年
  • ヴィジュアルでわかるバイオマテリアル
    古薗 勉; 岡田正弘 (担当:共編者(共編著者)範囲:)学研メディカル秀潤社 2006年12月
  • 未来を拓く研究者たちのドラマとその舞台 さきがけものがたり
    古薗 勉 (担当:分担執筆範囲:これが私の生きる道—感染防止デバイスの開発 病との闘い、研究、そして今—)アドスリー 2006年10月
  • ウイルスを用いない遺伝子導入法の材料、技術、方法論の新たな展開−先端生物医学研究・医療のための遺伝子導入テクノロジ− 遺伝子医学MOOK (5)
    木村 剛; 古薗 勉; 岸田晶夫 (担当:分担執筆範囲:遺伝子導入におけるセラミック材料−リン酸カルシウムを中心に−)メディカルドゥ発行 2006年
  • 図解高分子新素材のすべて
    古薗 勉 (担当:範囲:焼成アパタイト/ポリマー複合体-しなやかなセラミック材料から医療デバイスを創る-)工業調査会 2005年05月
  • ソフトナノテクノロジー —バイオマテリアル革命
    下村政嗣; 田中順三監修 (担当:分担執筆範囲:第1編 第5章 ナノ機能化経皮デバイス)シーエムシー出版 2005年
  • 人工臓器・再生医療の最先端
    古薗 勉 (担当:範囲:新しい生体/人工臓器インターフェイスとしてのナノ無機・有機複合材料)先端医療技術研究所 2005年
  • ナノバイオエンジニアリングマテリアル
    石原一彦監修 (担当:分担執筆範囲:ナノバイオエンジニアリングマテリアル, 第1編 バイオインターフェイス, 第8章 アパタイト単結晶体/ポリマー複合体界面の特性)フロンティア出版 2004年03月
  • 人工臓器はいま
    (担当:分担執筆範囲:人工腎臓 安定した治療実績をもつ人工臓器 透析患者の人生をサポートする,第１章 暮らしの中の人工臓器,)はる書房 2003年11月
  • インテリジェント材料・技術の最新開発動向
    古薗 勉; 岸田晶夫; 田中順三 (担当:分担執筆範囲:経皮デバイス)シーエムシー出版 2003年
  • 臨床工学技士標準テキスト
    (担当:分担執筆範囲:XIII. 生体材料工学)金原出版 2002年
  • 化学フロンティア３生体医工学基盤記述の確立と臨床応用を目指して
    田中順三; 古薗 勉 (担当:分担執筆範囲:新しいセラミックス関連材料の開発)化学同人 2001年
  • バイオミメティックスハンドブック
    田中順三; 古薗 勉 (担当:分担執筆範囲:バイオミネラリゼーションからバイオミメティックスへ（D. Walsh, S. Mann）)エヌ・ティー・エス 2000年09月
  • 無機・有機ハイブリッド材料の開発と応用
    古薗 勉; 玉田靖 (担当:分担執筆範囲:MPCおよびアパタイトとのシルクハイブリッド材料の開発)シーエムシー出版 2000年
  • 医療用高分子材料の開発と応用
    中林宣男 監修 (担当:分担執筆範囲:アラミド・シリコーン樹脂)シーエムシー出版 1998年03月
  • Functional Monomers and Polymers
    K. Takemoto, M. Kamachi and R. M. Ottenbrite (Eds.) (担当:分担執筆範囲:A novel biomaterial: aramid-silicone resin)Marcel Dekker Inc. 1997年 ISBN: 9780824799915
  • Advances in Polymeric Biomaterials Science
    T. Akaike, T. Okano, M. Akashi, M. Terano, N. Yui (Eds) (担当:分担執筆範囲:Surface properties of aramid-silicone resin)CMC Co., LTD. 1997年
  • Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems
    N. Ogata, S. W. Kim, J. Feijen and T. Okano (Eds.) (担当:分担執筆範囲:Adsorption of biomolecules onto multiblock copolymer consisting of aromatic polyamide and poly(dimethylsiloxane))Springer 1996年 ISBN: 9784431658856
  • Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems
    N. Ogata, S. W. Kim, J. Feijen and T. Okano (Eds.) (担当:分担執筆範囲:A novel biomaterial: Aramid-silicone resin)Springer 1996年 ISBN: 9784431658856
  • Surface Science of Crystalline Polymers
    M. Terano and N. Yui (Eds.) (担当:分担執筆範囲:Surface properties of poly(dimethylsiloxane)-polyamide multiblock copolymers (PAS))Kodansha Scientific Ltd. 1996年 ISBN: 9784906464029

MISC

  • （研究所めぐり）近畿大学生物理工学部医用工学科
    古薗 勉 人工臓器 51 (1) 82 -84 2022年06月
  • 在宅血液透析の普及に向けての技術革新
    古薗 勉 人工臓器 50 (3) 224 -227 2021年12月
  • 虚血下肢治療用足場微粒子の開発と効能
    古薗 勉; 福本真也; 佐藤秀樹; 山原研一 人工臓器 50 45 2021年
  • 在宅血液透析の安全性はどこまで担保すればいいのか？
    古薗 勉 日本在宅血液透析学会誌 1 (1) 6 -7 2020年09月
  • 自分の人生と照らし合わせて自分にあった治療を選ぶ
    古薗 勉 けんいち 健康生活マガジン「健康一番」 19 55 -59 2019年02月
  • 腎代替療法と就労
    古薗 勉 臨牀透析 35 1649 -1654 2019年
  • 経皮デバイスと感染
    古薗 勉; 舩渡川圭次; 切替照雄 人工臓器 47 216 -218 2018年
  • 古薗 勉; 福本真也 セラミックス 52 (3) 134 -137 2017年
  • さまざまな腎代替療法を受けての所感
    古薗勉 臨牀透析 33 685 -691 2017年 [招待有り]
  • 利用者の立場からみた在宅血液透析
    古薗勉 腎と透析 81 808 -812 2016年 [招待有り]
  • 透析療法up date：在宅血液透析は拡がるか？
    古薗勉 人工臓器2016第32回日本人工臓器学会教育セミナー 41 -48 2016年 [招待有り]
  • セラミックスを柔らかく使う 医療をかえる新しいナノテクノロジー
    古薗勉 ニュートン別冊 90 -93 2015年08月 [招待有り]
  • 抗感染性カテーテルの開発と在宅血液透析のバスキュラーアクセスを考える
    古薗勉 和歌山県臨床工学技士会会誌 6 19 -23 2015年 [招待有り]
  • 古薗勉 PHARM STAGE 14 (9) 28 -32 2014年 [招待有り]
  • 長時間透析に対応したリン添加透析液供給法の検討
    西手芳明; 竹澤真吾; 古薗 勉 近畿大学生物理工学部紀要 31 21 -30 2013年 [査読有り]
  • 微粒子安定化エマルションを利用する複合微粒子の創出
    藤井秀司; 岡田正弘; 古薗 勉 Cosmetic Stage 7 28 -36 2013年 [招待有り]
  • 家庭で行う人工腎臓治療：患者として経験した驚異の世界
    古薗勉 人工臓器 42 7 -9 2013年 [招待有り]
  • 相澤 守; 古薗 勉 人工臓器 41 (3) 207 -211 2012年12月 [招待有り]
  • 大森 裕子; 岡田 正弘; 古薗 勉; 武田 昭二; 松本 尚之 日本歯科理工学会誌 = The journal of the Japanese Society for Dental Materials and Devices 31 (5) 393 -393 2012年09月
  • 岡田 正弘; 藤井 秀司; 古薗 勉; 武田 昭二 日本歯科理工学会誌 = The journal of the Japanese Society for Dental Materials and Devices 31 (2) 107 -107 2012年03月
  • 我が国のend stage kidney disease (ESKD)の現状
    山縣邦弘; 八木澤 隆; 中井 滋; 中山昌明; 今井圓裕; 服部元史; 五十嵐 徹; 石村栄治; 井関邦敏; 伊丹儀友; 乳原善文; 笠井健司; 木全直樹; 剣持 敬; 佐古まゆみ; 杉山 斉; 鈴木洋通; 田邊一成; 椿原美治; 西 慎一; 樋之津史郎; 平松 信; 古薗 勉; 望月隆弘; 湯沢賢治; 横山 仁; 秋葉 隆; 高原史郎; 吉村了勇; 本田雅敬; 松尾清一; 秋澤忠男 透析会誌 45 1067 -1076 2012年
  • 超音波を用いた抗感染性カテーテルの開発
    新田尚隆; 古薗 勉 超音波テクノ 24 84 -88 2012年
  • 我が国のend stage kidney disease (ESKD)の現状
    山縣邦弘; 八木澤 隆; 中井 滋; 中山昌明; 今井圓裕; 服部元史; 五十嵐 徹; 石村栄治; 井関邦敏; 伊丹儀友; 乳原善文; 笠井健司; 木全直樹; 剣持 敬; 佐古まゆみ; 杉山 斉; 鈴木洋通; 田邊一成; 椿原美治; 西 慎一; 樋之津史郎; 平松 信; 古薗 勉; 望月隆弘; 湯沢賢治; 横山 仁; 秋葉 隆; 高原史郎; 吉村了勇; 本田雅敬; 松尾清一; 秋澤忠男 日児会誌 25 178 -189 2012年
  • 古薗 勉 バイオマテリアル : 生体材料 : journal of Japanese Society for Biomaterials 29 (4) 249 -253 2011年11月 [招待有り]
  • 在宅血液透析の血清リン値からみた透析時間・スケジュールの検討
    古薗 勉 クリニカルエンジニアリング 22 804 -809 2011年
  • 在宅血液透析を普及させるには
    古薗勉 臨牀透析 27 1383 2011年 [招待有り]
  • 就労と透析
    古薗勉 腎不全を生きる 44 9 -20 2011年 [招待有り]
  • 古薗 勉; 岡田 正弘 セラミックス 45 (8) 645 -650 2010年08月 [招待有り]
  • 岡田 正弘; 福本 真也; 三間 洋平; 藤井 秀司; 古薗 勉 バイオマテリアル : 生体材料 : Journal of Japanese Society for Biomaterials 28 (2) 88 -95 2010年04月
  • 頻回短時間透析の現状と問題点
    坂井瑠実; 喜田智幸; 喜田亜矢; 古薗 勉 臨床透析 26 169 -175 2010年 [招待有り]
  • ハイドロキシアパタイトのカテーテルへの応用
    古薗 勉; 岡田正弘; 小粥康充 日本接着学会誌 44 230 -237 2008年
  • 腎不全治療を取り巻く先端テクノロジー
    下条文武; 古薗 勉 日本透析医学会雑誌 41 353 -353 2008年
  • 経験に基づく在宅血液透析の実際と期待
    古薗 勉 臨床透析 24 1700 -1703 2008年
  • 岡田 正弘; 古薗 勉 マテリアルインテグレ-ション 20 (11) 113 -119 2007年11月
  • 細菌感染を工学的に考える：抗感染性長期留置型カテーテル実現への挑戦
    古薗 勉; 植木光樹; 岡田正弘; 小粥康充; 益田美和 ICUとCCU別冊 第17回日本急性血液浄化学会Proceedings-2006 3 -5 2007年
  • 医療機器の素材としての有機−ナノ無機ハイブリッド材料
    古薗 勉; 岡田正弘 高分子 56 129 -132 2007年
  • ソフトナノセラミック・プロセッシングによる医療機器の開発
    古薗 勉; 益田美和; 岡田正弘; 小粥康充 SPUTTERING&PLASMA PROCESSES 22 23 -30 2007年
  • カテーテル用材料の最新技術
    岡田正弘; 益田美和; 古薗 勉 工業材料 55 32 -35 2007年
  • 出口部肉芽に対する硝酸銀処置方法の検討
    二上志帆子; 猪田恵美子; 梶應陽子; 田畑勉; 益田美和; 古薗 勉 腎と透析 63 (別冊) 243 -245 2007年
  • 臨床工学技士のためのバイオマテリアル(連載第3回)：バイオマテリアルに求められる生体適合性
    岡田正弘; 古薗 勉 クリニカルエンジニアリング 17 75 -81 2006年
  • 臨床工学技士のためのバイオマテリアル(連載第4回)：高分子系バイオマテリアルの基礎から医療応用まで
    岡田正弘; 古薗 勉 クリニカルエンジニアリング 17 285 -294 2006年
  • 臨床工学技士のためのバイオマテリアル(連載第5回)：セラミックス系バイオマテリアルの基礎から医療応用まで
    岡田正弘; 古薗 勉 クリニカルエンジニアリング 17 517 -523 2006年
  • 臨床工学技士のためのバイオマテリアル(連載第6回)：金属系バイオマテリアルの基礎から医療応用まで
    岡田正弘; 古薗 勉 クリニカルエンジニアリング 17 762 -772 2006年
  • 臨床工学技士のためのバイオマテリアル(連載第7回)：再生医療におけるバイオマテリアルの位置付け
    岡田正弘; 古薗 勉 クリニカルエンジニアリング 17 981 -990 2006年
  • 臨床工学技士のためのバイオマテリアル(連載第8回)：近未来に登場する先端バイオマテリアル
    岡田正弘; 古薗 勉 クリニカルエンジニアリング 17 1250 -1264 2006年
  • 再生医療：ナノアパタイト, 特集ナノメディシンパート2
    古薗 勉; 岸田晶夫 バイオインダストリー5月号 54 -59 2005年
  • 生体接着性と抗菌性を発現する新規なカテーテル複合材料
    古薗 勉; 岡田正弘 特集バイオセラミックス, 月刊マテリアルインテグレーション 18 (6) 46 -49 2005年
  • 臨床工学技士のためのバイオマテリアル(連載第1回)：バイオマテリアルとしての条件と医療用デバイス
    岡田正弘; 古薗 勉 クリニカルエンジニアリング 16 959 -966 2005年
  • 臨床工学技士のためのバイオマテリアル(連載第2回)：バイオマテリアルの安全性の確保とその評価法
    岡田正弘; 古薗 勉 クリニカルエンジニアリング 16 1176 -1183 2005年
  • ナノセラミックス複合体による循環器系デバイスの創出：細菌感染防止用経皮デバイスを目指して
    古薗 勉; 京谷晋吾; 岸田晶夫; 田中順三 循環器病研究の進歩(通巻44号) ⅩⅩⅤ (1) 71 -78 2004年11月
  • 再生医療に必要なバイオインターフェイスの創製
    古薗 勉; 田中順三; 岸田晶夫 ICUとCCU 27 (別冊) S12 -S14 2003年
  • 人工腎臓
    古薗 勉 人工臓器32刊 3 213 -216 2003年
  • 細菌感染抑制作用と感染時に殺菌作用を発現する次世代型体内留置カテーテルの開発
    古薗 勉 医科学応用研究財団研究報告, 鈴木謙三記念 2003年
  • 古薗 勉; 岸田晶夫; 田中順三 工業材料 50 (6) 76 -80 2002年
  • バイオセラミックスの開発動向−有機複合体への新しい試み−
    古薗 勉; 菊池正紀; 田中順三 FINE CERAMICS REPORT(FCレポート) 18 (2) 38 -42 2000年
  • 明石満; 古薗 勉; 松本竹男; 岸田晶夫 高分子加工 45 (3) 124 -130 1996年
  • 明石満; 岸田晶夫; 古薗 勉 化学 50 (8) 522 -523 1995年
  • 古薗 勉; 岸田晶夫; 明石満; 丸山征郎; 宮崎剛; 鯉沼康美; 松本竹男 人工臓器 22 (2) 370 -375 1993年

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2022年04月 -2025年03月 
    代表者 : 古薗 勉; 東 慶直
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2019年04月 -2022年03月 
    代表者 : 古薗 勉; 東 慶直
     
    本研究課題では、体内必須元素の亜鉛(Zn)に着目し、当該金属元素をハイドロキシアパタイト(HAp)結晶構造中に置換したZnドープHAp(Zn-HAp)ナノ粒子を創出し、当該ナノ粒子の材料特性評価、高分子複合化、アナフィラキシー（様）反応評価、抗菌メカニズム評価等を行い、新規な概念を有する抗感染性ナノ材料の開発および抗菌メカニズムの解明を行った。具体的には、結晶性・分散性Zn-HApナノ粒子合成法・コーティング法の確立、、抗菌活性評価・持続性、およびイオン交換・活性酸素種蓄積の現象解明について明らかにした。以上から、抗菌持続性とアレルギー反応を起こしにくいナノ材料の創出を達成した。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 古薗 勉; 東 慶直
     
    当該研究課題では、Fイオンをドープした分散性と結晶性が高く、微弱な抗菌性を有しアナフィラキシー（様）反応を回避するF-HApナノ粒子を開発し、新規な抗感染性カテーテル創出のための基盤技術を確立した。当該ナノ粒子の性能評価として、Fイオンの放出挙動、病原性微生物を用いた抗菌性評価、線維芽細胞(L929細胞)を用いた接着性評価、およびプロトタイプ作製のためのカテーテル素材へのコーティング（複合化）の検討を実施した。以上の結果から、多種の細菌に微弱な抗菌性を有しつつも正常細胞に対して毒性が低く、またカテーテル素材へのコーティング好適な抗菌性ナノ粒子の創出を達成した。
  • 日本学術振興会：科学研究費助成事業 挑戦的萌芽研究
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 本田 義知; 古薗 勉
     
    口腔癌などで生じた骨欠損修復において、力学刺激が負荷された部位での骨再生は今だ困難を極める。その一因として、細胞が力学刺激を感知するメカニズムの解明が未だ発展途上にあり、特に、細胞核の変形に起因する遺伝子発現の変化に関する研究が黎明期にあることがあげられる。もし、新たな評価法が開発され同メカニズムの解明が加速すれば、将来的に新たな再生治療の開発に繋がり患者の生活の質的向上へ大きく寄与できる。本研究期間では、細胞核が接着しかつ伸縮可能な細胞核結合シートの合成と材料学的評価を行った。更に、細胞核抽出法の検討と、同シート上での細胞核の伸展の可否を確認した。
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 坂井 加奈; 本田 義知; 古薗 勉
     
    矯正治療に伴う人為的歯根吸収のメカニズムは未だ完全に解明されておらず、生来歯根の短い患者などは治療の選択肢が制限されている。もし、人為的歯根吸収を誘導する歯周組織の細胞応答機序をIn vitroで「簡便かつ正確に」解明出来る基盤研究ツールが開発されれば、新規メカニズム解明や治療法の開発に繋がり、治療を享受出来る患者数の増大に大きく寄与できる。本研究では、高分子膜上に硬組織成分同様のナノリン酸カルシウム（Nano-CaP）を強固に固定した高分子膜を基盤に、力学的刺激可能な歯周組織構造を模倣した2次元細胞培養デバイスの創製を試みた。同膜上での多様な細胞種の細胞接着・伸展挙動を確認した。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2013年04月 -2016年03月 
    代表者 : 古薗 勉; 東 慶直
     
    当該研究課題では、細胞毒性を抑制し微弱な抗菌性を有する新規材料を創出することを目的とする。分散性および結晶性に優れるハイドロキシアパタイト(HAp)に銀イオンをドープしたAg-HApナノ粒子の合成、コーティング特性の検討、材料特性および生物学的評価を行った。 融着防止法により分散性に優れた結晶性Ag-HApナノ粒子を得ることができた。また、高分子基材へのコーティング特性にも優れていた。大腸菌および緑膿菌に対する抗菌性が認められた。ヒト咽頭がん由来線維芽細胞を用いた接着性評価にて、培養床と同様の細胞接着性が認められた。以上より、細胞毒性を低減させたコーティング用抗菌ナノ粒子の創出を達成した。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2008年 -2010年 
    代表者 : 福本 真也; 小山 英則; 古薗 勉; 岡田 正弘
     
    重症虚血肢に対する細胞移植による血管新生療法の効果は十分とは言えず、効果を増幅する技術が必要である。我々は移植細胞を局所に維持する細胞足場としてナノサイズのハイドロキシアパタイト単結晶体を被覆したポリ乳酸球状体(ナノスキャフォールド)を開発した。ナノスキャフォールドを骨髄単核細胞と混合して移植することで細胞を移植局所(筋肉組織内)に長期間担持し、血管新生療法の効果を増幅することを示した。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2007年 -2009年 
    代表者 : 古薗 勉; 岡田 正弘; 益田 美和
     
    ハイドロキシアパタイト(HAp)ナノ単結晶(粒子)を被覆した複合材料表面の細胞機能を詳細に検討した。HAp被覆シートでは未処理ポリエチレンテレフタレート(PET)シートより高い細胞接着性および増殖性を示した。細胞の強固な接着は、HApのナノ構造に起因する細胞のアンカリングと細胞外マトリックスのリモデリングが積極的に行われていることによると推察された。
  • 日本学術振興会：科学研究費助成事業 基盤研究(B)
    研究期間 : 2004年 -2006年 
    代表者 : 岸田 晶夫; 古薗 勉; 山岡 哲二; 木村 剛
     
    超高圧処理を用いた分子集合化技術による新しい遺伝子送達用複合体の開発について検討している。今年度は、(1)ポリビニルアルコール以外の高分子による遺伝子複合化の検討、(2)水素結合性を有する無機微粒子の応用、について検討を行った。水素結合性高分子として、デキストランをはじめとする多糖類、アクリルアミド、アクリル酸、ポリエチレングリコール、低分子量ポリハイドロキシエチルメタクリレートを用いて、DNAとの複合化を検討した。超高圧処理よって、明確な複合化が観察できたのはデキストランとポリエチレングリコールであった。これら2種の高分子について、プラスミドDNAとの複合化を検討したところ、溶解する溶液の状態によって、複合化が多きく影響されることが明らかになった。すなわち、精製した水に空気中の炭酸ガスがいったん溶解したものについては、複合化が阻害された。この結果から、ポリビニルアルコールよりも水素結合性が弱い高分子については、複合化の際の条件設定をより厳密に行う必要があることがわかった。無機微粒子の表面には水酸基を有するものがあり、これを利用したDNAの複合化についても検討を行った。水溶液中で分散性を保ち、かつ水酸基を表面に有する生体材料である、ハイドロキシアパタイトのナノメートルサイズの微粒子を作成し、複合化について検討した。DNAの複合化は比較的安定しており、細胞デリバリーの実験も行えた。プラスミドDNAの取り込みついては、十分と考えられる量が取り込まれていたが、コードタンパク質の発現量は低かった。これらの結果より、DNA複合化の際の条件の精緻な検討と、細胞内に取り込まれた後の核への移行について、新しい機構を組み込む必要があると考えられた。候補物質としては超高圧処理でも構造が影響を受けない、低分子ペプチドを考えている。
  • 日本学術振興会：科学研究費助成事業 基盤研究(B)
    研究期間 : 2001年 -2003年 
    代表者 : 古薗 勉; 岸田 晶夫
     
    医療領域において、ポリテトラフルオロエチレン(PTFE)製人工血管が知られている。しかしながら、PTFEは生体内でねじれによる阻血を生じることがしばしば臨床上の問題とされている。本課題では、PTFEをはじめとする含フッ素ポリマーが有する低強度の欠点を補うため、高強度の特性を有するアラミドと複合化した含フッ素ブロック共重合体を合成することによって、新規な人工血管用材料を創製することを目的とする。この目的に基づき、ブロック共重合体の合成、表面解析及び物性評価を主たる実験計画目標とした。 1)含フッ素ブロック共重合体の合成: まず、両末端にアミノ基を有する含フッ素芳香族モノマーを合成し、これと芳香族ジカルボン酸クロリドとを重縮合させ目的とするブロック共重合体の合成を行った[特願2002-252183、J.Polym.Sci.,Part A : Polym.Chem.,41,2840(2003)]。さらに、アラミド部分の鎖長を延伸したブロック共重合体の合成を2段階縮合法により行った(J.Polym.Sci.,Part A : Polym.Chem.,投稿中)。その結果、それぞれ数平均分子量が17,000および20,000以上の高分子量体を得ることに成功した。この共重合体をもとにキャスト法によりフィルム作成を試みた。均一な厚さのフィルムが得られたが、ひびが入りやすい等、十分な強度を有するものではなかった。 2)表面特性の解析、物性評価等: 表面解析や引張試験等の物性評価を計画していたが、合成およびフィルム作成に多くの時間を要したため、これらの評価には至らなかった。フッ素、アラミド各ブロックの配分調整により適度な強度を有する共重合体の合成は可能であると考えられ、その点を克服することにより、この高分子の人工血管用材料への発展も期待できる。
  • 日本学術振興会：科学研究費助成事業 基盤研究(B)
    研究期間 : 1999年 -2001年 
    代表者 : 岸田 晶夫; 中山 泰秀; 芹澤 武; 明石 満; 古薗 勉
     
    (1)スルホン化ポリ(γ-グルタミン酸)の生物学的活性の検討 昨年度までに確立した合成法によって調製したスルホン化ポリ(γ-グルタミン酸)を用いて生物学的活性(抗血栓性と細胞増殖促進効果)を検討した。抗血栓性については、ヘパリンと比較すると非常に弱い活性を有していた。これは抗凝固剤としての利用は不適であるが、創傷部位への投与を行っても凝固を阻害せず、硫酸基の存在によって増殖因子活性化を行える可能性を示している。細胞増殖促進効果に関しては、ヘパリンと同等の活性をゆうしていることを明らかにした。他の硫酸化・スルホン化高分子と比較すると、検討した中で最も高い活性を有していることが明らかになった。 (1)機能性ポリ(γ-グルタミン酸)を用いた無血清培養系の基礎検討 スルホン化ポリ(γ-グルタミン酸)を用いた無血清培養系の開発のための基礎検討を行った。添加する増殖因子としてbFGFを用いることで、血清添加系にほぼ匹敵する無血清培養が可能であることを示した。これにより、無血清および血清存在下のいずれに於いても活性が認められ、生分解性増殖促進剤としての機能が期待できた。 (2)スルホン化ポリ(γ-グルタミン酸)ハイドロゲルの調製とその評価 再生医療に用いる際には、生体内で長時間増殖因子を活性化する機能が必要である。ポリ(γ-グルタミン酸)ハイドロゲルの調製法について検討し、スルホン化ポリ(γ-グルタミン酸)を混合することで、bFGF活性能を有するハイドロゲルを得ることが出来た。

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