KINDAI UNIVERSITY


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FURUZONO Tsutomu

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FacultyDepartment of Biomedical Engineering / Graduate School of Biology-Oriented Science and Technology
PositionProfessor
Degree
Commentator Guidehttps://www.kindai.ac.jp/meikan/603-furuzono-tsutomu.html
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Last Updated :2020/09/30

Education and Career

Academic & Professional Experience

  •   2010 ,  - 現在, Faculty of Biology-Oriented Science and Technology, Department of Biomedical Engineering, Kindai University

Research Activities

Research Areas

  • Life sciences, Biomaterials
  • Life sciences, Biomedical engineering
  • Life sciences, Biomaterials
  • Life sciences, Biomedical engineering

Published Papers

  • Preparation and application of a potassium-substituted calcium phosphate sheet as a dental material for tissue dentin hypersensitivity, N. Kato, Y. Hatoko, E. Yamamoto, T. Furuzono, S. Hontsu, Key Eng. Mater., Key Eng. Mater., 720, 102 - 107, 2016 , Refereed
  • Influence of calcination conditions on dispersiblity and chemical composition of hydroxyapatite crystals calcined with anti-sintering agents, M. Okada, Y. Omori, M. Awata, T. Shirai, N. Matsumoto, S. Takeda, T. Furuzono, J. Nanoparticle Res., J. Nanoparticle Res., 16, 2469 - 2477, 2014 , Refereed
  • Hydroxyapatite-coated poly(E-caprolactone) microspheres fabricated via a Pickering emulsion route: effect of fabrication parameters on diameter and chemical composition, Syuji Fujii, Masahiro Okada, Taiki Nishimura, Tatsuya Sugimoto, Hayata Maeda, Hiroyuki Hamasaki, Tsutomu Furuzono, Yoshinobu Nakamura, COMPOSITE INTERFACES, COMPOSITE INTERFACES, 20(1), 45 - 56, Feb. 2013 , Refereed
    Summary: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.
  • Development of Microspheres with Hydroxyapatite Nanocrystals as Cell Scaffold for Angiogenesis, T. Iwamoto, T. Terada, Y. Kogai, M. Okada, T. Furuzono, Funct. Mater. Lett., Funct. Mater. Lett., 5(1260010), 1 - 6, 2012 , Refereed
  • 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, J. Drug Delivery, 2011(962743), 1 - 8, 2011 , Refereed
  • In vitro secretion of TNF-alpha from bone marrow mononuclear cells incubated on amino group modified TiO2 nano-composite under ultrasound irradiation, T. Furuzono, M. Masuda, N. Nitta, A. Kaya, T. Yamane, M. Okada, MATERIALS SCIENCE AND ENGINEERING B-ADVANCED FUNCTIONAL SOLID-STATE MATERIALS, MATERIALS SCIENCE AND ENGINEERING B-ADVANCED FUNCTIONAL SOLID-STATE MATERIALS, 173(1-3), 191 - 194, Oct. 2010 , Refereed
    Summary: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.
  • Fundamental study on activation of titanium dioxide composite irradiated by low-intensity focused ultrasound in anti-infective catheter system, N. Nitta, A. Kaya, T. Yamane, K. Kyodo, M. Okada, T. Furuzono, Jpn. J. Appl. Phys., Jpn. J. Appl. Phys., 49, 07HF24-1 - 7, 2010 , Refereed
  • Preparation and Characterizations of Dispersible Fluorinated Hydroxyapatite Nanoparticles with Weak Antibacterial Activity, Tsutomu Furuzono, Yoshinao Azuma, Yuichi Niigawa, Yasumichi Kogai, Yoshiki Sawa, ASAIO JOURNAL, ASAIO JOURNAL, 62(2), 197 - 202, Mar. 2016 , Refereed
    Summary: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.
  • Newly Developed Biocompatible Material: Dispersible Titanium-Doped Hydroxyapatite Nanoparticles Suitable for Antibacterial Coating on Intravascular Catheters, Tsutomu Furuzono, Masatoshi Okazaki, Yoshinao Azuma, Mitsunobu Iwasaki, Yasumichi Kogai, Yoshiki Sawa, Contributions to Nephrology, Contributions to Nephrology, 189, 144 - 152, 2016 , Refereed
    Summary: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.
  • Synthesis and antibacterial evaluation of calcinated Ag-doped nano-hydroxyapatite with dispersibility, Tsutomu Furuzono, Mazumder Motaharul, Yasumichi Kogai, Yoshinao Azuma, Yoshiki Sawa, INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS, INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS, 38(5), 251 - 258, May 2015 , Refereed
    Summary: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.
  • Injectable cell scaffold restores impaired cell-based therapeutic angiogenesis in diabetic mice with hindlimb ischemia, 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, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 454(1), 119 - 124, Nov. 2014 , Refereed
    Summary: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.
  • Prevention of catheter infection using a biodegradable tissue adhesive composed of human serum albumin and disuccinimidyl tartrate, 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, JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS, 29(3), 284 - 297, May 2014 , Refereed
    Summary: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.
  • Preparation of carboxylated Ag nanoparticles as a coating material for medical devices and control of antibacterial activity, Tsutomu Furuzono, Takashi Iwamoto, Yoshinao Azuma, Masahiro Okada, Yoshiki Sawa, JOURNAL OF ARTIFICIAL ORGANS, JOURNAL OF ARTIFICIAL ORGANS, 16(4), 451 - 457, Dec. 2013 , Refereed
    Summary: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.
  • Effect of interfacial serum proteins on melanoma cell adhesion to biodegradable poly(L-lactic acid) microspheres coated with hydroxyapatite, Hiroyuki Shinto, Takuya Hirata, Tomonori Fukasawa, Syuji Fujii, Hayata Maeda, Masahiro Okada, Yoshinobu Nakamura, Tsutomu Furuzono, COLLOIDS AND SURFACES B-BIOINTERFACES, COLLOIDS AND SURFACES B-BIOINTERFACES, 108, 8 - 15, Aug. 2013 , Refereed
    Summary: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.
  • In vitro degradation of hydroxyapatite nanoparticle-coated biodegradable microspheres, Syuji Fujii, Yuki Miyanari, Taiki Nishimura, Yuichi Yokoyama, Sho Hamasaki, Masahiro Okada, Tsutomu Furuzono, Shojiro Matsuda, Hideki Takamori, Yoshinobu Nakamura, POLYMER DEGRADATION AND STABILITY, POLYMER DEGRADATION AND STABILITY, 98(1), 377 - 386, Jan. 2013 , Refereed
    Summary: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.
  • Solvent-free formation of hydroxyapatite coated biodegradable particles via nanoparticle-stabilized emulsion route, Masahiro Okada, Syuji Fujii, Taiki Nishimura, Yoshinobu Nakamura, Shoji Takeda, Tsutomu Furuzono, APPLIED SURFACE SCIENCE, APPLIED SURFACE SCIENCE, 262, 39 - 44, Dec. 2012 , Refereed
    Summary: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.
  • Formation of Pickering Emulsions Stabilized via Interaction between Nanoparticles Dispersed in Aqueous Phase and Polymer End Groups Dissolved in Oil Phase, Masahiro Okada, Hayata Maeda, Syuji Fujii, Yoshinobu Nakamura, Tsutomu Furuzono, LANGMUIR, LANGMUIR, 28(25), 9405 - 9412, Jun. 2012 , Refereed
    Summary: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.
  • Enhancement of Cell-Based Therapeutic Angiogenesis Using a Novel Type of Injectable Scaffolds of Hydroxyapatite-Polymer Nanocomposite Microspheres, Yohei Mima, Shinya Fukumoto, Hidenori Koyama, Masahiro Okada, Shinji Tanaka, Tetsuo Shoji, Masanori Emoto, Tsutomu Furuzono, Yoshiki Nishizawa, Masaaki Inaba, PLOS ONE, PLOS ONE, 7(4), 1 - 12, Apr. 2012 , Refereed
    Summary: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.
  • Preparation and in vitro/in vivo evaluations of dimpled poly(l-lactic acid) fibers mixed/coated with hydroxyapatite nanocrystals, Hiroshi Yanagida, Masahiro Okada, Miwa Masuda, Isao Narama, Shigeyuki Nakano, Satoshi Kitao, Kazuo Takakuda, Tsutomu Furuzono, JOURNAL OF ARTIFICIAL ORGANS, JOURNAL OF ARTIFICIAL ORGANS, 14(4), 331 - 341, Dec. 2011 , Refereed
    Summary: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.
  • Low-temperature synthesis of nanoparticle-assembled, transparent, and low-crystallized hydroxyapatite blocks, Masahiro Okada, Tsutomu Furuzono, JOURNAL OF COLLOID AND INTERFACE SCIENCE, JOURNAL OF COLLOID AND INTERFACE SCIENCE, 360(2), 457 - 462, Aug. 2011 , Refereed
    Summary: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.
  • Release Behavior from Hydrogen-Bonded Polymer Gels Prepared by Pressurization, Shingo Mutsuo, Kazuya Yamamoto, Tsutomu Furuzono, Tsuyoshi Kimura, Tsutomu Ono, Akio Kishida, JOURNAL OF APPLIED POLYMER SCIENCE, JOURNAL OF APPLIED POLYMER SCIENCE, 119(5), 2725 - 2729, Mar. 2011 , Refereed
    Summary: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
  • Hydroxyapatite/biodegradable poly(L-lactide-co-epsilon-caprolactone) composite microparticles as injectable scaffolds by a Pickering emulsion route, Xiangwen Liu, Masahiro Okada, Hayata Maeda, Syuji Fujii, Tsutomu Furuzono, ACTA BIOMATERIALIA, ACTA BIOMATERIALIA, 7(2), 821 - 828, Feb. 2011 , Refereed
    Summary: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.
  • Pickering-Type Water-in-Oil-in-Water Multiple Emulsions toward Multihollow Nanocomposite Microspheres, Hayata Maeda, Masahiro Okada, Syuji Fujii, Yoshinobu Nakamura, Tsutomu Furuzono, LANGMUIR, LANGMUIR, 26(17), 13727 - 13731, Sep. 2010 , Refereed
    Summary: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.
  • In Vivo Evaluation of Hydroxyapatite Nanocoating on Polyester Artificial Vascular Grafts and Possibility as Soft-Tissue Compatible Material, Hiroyuki Kadono, Tsutomu Furuzono, Miwa Masuda, Masahiro Okada, Mitsuki Ueki, Keiichi Takamizawa, Ryoichi Tanaka, Kunio Miyatake, Yoshihisa Koyama, Kazuo Takakuda, ASAIO JOURNAL, ASAIO JOURNAL, 56(1), 61 - 66, Jan. 2010 , Refereed
    Summary: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.

Books etc

  • Biomimetics: Advancing Nanobiomaterials and Tissue Engineering, S. Fujii, M. Okada, T. Furuzono, Contributor, Hydroxyapatite-biodegradable polymer nanocomposite microspheres toward injectable cell scaffold, John Wiley & Sons, Inc.,   2013

Misc

  • 我が国のend stage kidney disease (ESKD)の現状, 25, 178, 189,   2012
  • Hydroxyapatite nanoparticles: fabrication methods and medical applications, M. Okada, T. Furuzono, 13, 064103, 1, 14,   2012 , 招待有り, 10.1088/1468-6996/13/6/064103
  • Infection at cardiovascular area, especially catheter-related infection, FURUZONO Tsutomu, 29, 4, 249, 253,   2011 11 , 招待有り, http://ci.nii.ac.jp/naid/10030203296
  • 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,   2011
  • Hybrid Materials Coated with Hydroxyapatite Nanocrystals as Soft-tissue Compatible Bio-ceramics, FURUZONO Tsutomu, OKADA Masahiro, Ceramics Japan, 45, 8, 645, 650,   2010 08 01 , 招待有り, http://ci.nii.ac.jp/naid/10026496533
  • Development of hydroxyapatite-nanocrystal-coated microspheres for therapeutic angiogenesis using cell transplantation, OKADA Masahiro, FUKUMOTO Shinya, MIMA Yohei, FUJII Syuji, FURUZONO Tsutomu, Journal of Japanese Society for Biomaterials, 28, 2, 88, 95,   2010 04 28 , http://ci.nii.ac.jp/naid/10026241778
  • A novel approach to prepare hydroxyapatite-coated biodegradable polymer microspheres loaded with magnetic Fe3O4 via nanoparticle-stabilized emulsions, Masahiro Okada, Shoji Takeda, Tsutomu Furuzono, Key Engineering Materials, 529-530, 1, 223, 228,   2013 , 招待有り, 10.4028/www.scientific.net/KEM.529-530.223
    Summary: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 Fe 3O4 particles was a key factor to prepare stable HAp-nanoparticle-stabilized oil droplets (and HAp-nanoparticle-coated polymer microspheres) loaded with magnetic Fe3O4 particles. © (2013) Trans Tech Publications, Switzerland.