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Shitomi Kanako

Faculty of Dental Medicine　Division of Dental Medicine　Department of Health ScienceAssistant Professor
Hokkaido University HospitalAssistant Professor

Researcher basic information

■ Degree
  • Ph.D., Hokkaido University
■ URL
researchmap URLホームページURL■ Various IDs
J-Global ID■ Educational Organization

Research activity information

■ Papers
  • Antibacterial crystalline bilayers constructed on dentin substrates via laser-assisted mineralization: characterization and functional implications
    Kazuo Onuma; Miyabi Makino; Maki Nakamura; Erika Nishida; Kanako Shitomi; Saori Tanaka; Hirofumi Miyaji; Ayako Oyane
    APPLIED SURFACE SCIENCE, 711, 01 Dec. 2025
    English, Scientific journal
  • Integration of dual drugs into a collagen scaffold by a combination of apatite coating and impregnation with apatite particles for periodontal regeneration.
    Kaushita Banerjee; Ayako Oyane; Maki Nakamura; Tomoya Inose; Erika Nishida; Kanako Shitomi; Hirofumi Miyaji
    RSC advances, 15, 24, 19480, 19488, 04 Jun. 2025, [International Magazine]
    English, Scientific journal, Bioresorbable porous scaffolds capable of promoting osteoregeneration while preventing bacterial infection are needed for regenerative periodontal therapy. Previously, a porous collagen sponge coated with low-crystalline apatite has been shown to possess superior bioresorption and osteogenic properties compared to the uncoated sponge. In this study, we integrated osteogenic and antibacterial dual drugs into the sponge utilizing two types of apatite matrices to achieve further functionalization. First, the collagen sponge was coated with apatite loaded with an osteogenic drug, l-ascorbic acid 2-phosphate (AS), using a metastable supersaturated calcium phosphate (CaP) solution supplemented with AS. Second, the coated sponge was impregnated with apatite particles loaded with an antibacterial drug, ciprofloxacin (CF), which were fabricated using a labile supersaturated CaP solution supplemented with CF. The resulting dual drug-immobilized sponge demonstrated biological activities arising from both AS and CF; it enhanced proliferation of osteoblastic MC3T3-E1 cells and exhibited antibacterial activity against the oral bacterium Actinomyces naeslundii. The proposed technique to fabricate multifunctional scaffolds would offer a solution to provide more effective, patient-tailored regenerative periodontal therapy.
  • Fluoridated Apatite Coating on Human Dentin via Laser-Assisted Pseudo-Biomineralization with the Aid of a Light-Absorbing Molecule
    Ayako Oyane; Ikuko Sakamaki; Maki Nakamura; Kenji Koga; Kanako Shitomi; Saori Tanaka; Hirofumi Miyaji
    International Journal of Molecular Sciences, 23, 24, 15981, 15981, MDPI AG, 15 Dec. 2022, [Peer-reviewed]
    Scientific journal, A simple, area-specific coating technique for fluoridated apatite (FAp) on teeth would be useful in dental applications. Recently, we achieved area-specific FAp coating on a human dentin substrate within 30 min by a laser-assisted biomimetic (LAB) process; pulsed Nd:YAG laser irradiation in a fluoride-containing supersaturated calcium phosphate solution (FCP solution). The LAB-processed, FAp-coated dentin substrate exhibited antibacterial activity against a major oral bacterium, Streptococcus mutans. In the present study, we refined the LAB process with a combination of a dental diode laser and a clinically approved light-absorbing molecule, indocyanine green (ICG). A micron-thick FAp layer was successfully formed on the dentin surface within only 3 min by the refined LAB process, i.e., dental diode laser irradiation in the FCP solution following ICG treatment. The ICG layer precoated on the dentin substrate played a crucial role in inducing rapid pseudo-biomineralization (FAp layer formation) on the dentin surface by absorbing laser light at the solid-liquid interface. In the refined LAB process, the precoated ICG layer was eliminated and replaced with the newly formed FAp layer composed of vertically oriented pillar-like nanocrystals. Cross-sectional ultrastructural analysis revealed a smooth interface between the FAp layer and the dentin substrate. The refined LAB process has potential as a tool for the tooth surface functionalization and hence, is worth further process refinement and in vitro and in vivo studies.
  • Sustained antibacterial coating with graphene oxide ultrathin film combined with cationic surface-active agents in a wet environment.
    Hirofumi Miyaji; Yukimi Kanemoto; Asako Hamamoto; Kanako Shitomi; Erika Nishida; Akihito Kato; Tsutomu Sugaya; Saori Tanaka; Natsuha Aikawa; Hideya Kawasaki; Syun Gohda; Hironobu Ono
    Scientific reports, 12, 1, 16721, 16721, 18 Oct. 2022, [International Magazine]
    English, Scientific journal, Antimicrobial surfactants contained in mouthrinse have excellent efficacy, but are not retained on the tooth surface (are rinsed away) due to their low water resistance and thus do not exhibit sustained antibacterial activity. We have developed a new coating method using graphene oxide (GO) that retains the surfactant on the tooth surface even after rinsing with water, thus providing a sustained antibacterial effect. Ultra-thin films of GO and an antimicrobial agent were prepared by (1) applying GO to the substrate surface, drying, and thoroughly rinsing with water to remove excess GO to form an ultrathin film (almost a monolayer, transparent) on the substrate surface, then (2) applying antimicrobial cationic surface active agents (CSAAs) on the GO film to form a composite coating film (GO/CSAA). GO/CSAA formation was verified by scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, and ζ-potential and contact angle measurements. GO/CSAA was effective at inhibiting the growth of oral pathogens for up to 7 days of storage in water, and antibacterial activity was recovered by reapplication of the CSAA. Antibacterial GO/CSAA films were also formed on a tooth substrate. The results suggest that GO/CSAA coatings are effective in preventing oral infections.
  • Antibacterial and Antibiofilm Photodynamic Activities of Lysozyme-Au Nanoclusters/Rose Bengal Conjugates.
    Ichie Okamoto; Hirofumi Miyaji; Saori Miyata; Kanako Shitomi; Tsutomu Sugaya; Natsumi Ushijima; Tsukasa Akasaka; Satoshi Enya; Satoshi Saita; Hideya Kawasaki
    ACS omega, 6, 13, 9279, 9290, 06 Apr. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Antibacterial photodynamic therapy (aPDT) utilizes reactive oxygen species such as singlet oxygen (1O2) and free radicals via photosensitizers, which are light and light-sensitive agents, to reduce bacterial infections. It has been utilized as a treatment for dental diseases in place of antibiotic therapies. However, aPDT does not always cause the desired therapeutic effect due to the instability of organic photosensitizers and the formation of bacterial biofilms. To promote the antibacterial and antibiofilm effects of aPDT, we have proposed a lysozyme (Lys)-gold nanoclusters (Au NCs)/rose bengal (Lys-Au NCs/RB) conjugate as a novel photosensitizer. This conjugate was found to effectively impede the growth of both gram-positive and gram-negative bacteria when exposed to white light-emitting diode (LED) irradiation. The photoexcited Lys-Au NCs/RB showed significantly higher antibacterial activity than photoexcited Lys-Au NCs or RB alone. The synergistic effect is a result of the combination of Lys (an antibacterial protein) and enhanced 1O2 generation related to resonance energy transfer (RET) in the Au NCs/RB conjugate. Photoexcited Lys-Au NCs/RB increased the effects of aPDT in a dose- and time-dependent manner. Furthermore, the photoexcited Lys-Au NCs/RB successfully decreased Streptococcus mutans biofilm formation. However, in contrast, it did not have a negative effect on the proliferation, adhesion, or spread of mammalian cells, indicating low cytotoxicity. Lys-Au NCs/RB is a novel photosensitizer with low cytotoxicity that is capable of bacterial inactivation and the suppression of biofilm formation, and could help to improve dental treatments in the future.
  • Antibacterial coating of tooth surface with ion-releasing pre-reacted glass-ionomer (S-PRG) nanofillers
    Mayumi Kayoko; Miyaji Hirofumi; Miyata Saori; Nishida Erika; Furihata Tomokazu; Kanemoto Yukimi; Sugaya Tsutomu; Shitomi Kanako; Akasaka Tsukasa
    Heliyon, 7, 2, e06147, Elsevier, Feb. 2021, [Peer-reviewed]
    English
  • Evaluation of antibacterial and cytocompatible properties of multiple-ion releasing zinc-fluoride glass nanoparticles
    NISHIDA Erika; MIYAJI Hirofumi; SHITOMI Kanako; SUGAYA Tsutomu; AKASAKA Tsukasa
    Dental Materials Journal, 40, 1, 157, 164, Japanese Society for Dental Materials and Devices, 2021, [Peer-reviewed]
    English,

    Zinc-fluoride glass nanoparticles (Zinc-F) release several ions, such as fluoride, zinc and calcium ions, through acid-base reactions. The aim of this study was to evaluate the antibacterial and cytotoxic properties of Zinc-F. Antibacterial tests showed that a Zinc-F eluting solution significantly reduced the turbidity and colony-forming units of Streptococcus mutans and Actinomyces naeslundii, compared to that of calcium-fluoroaluminosilicate glass nanoparticles without zinc ions. In live/dead staining, Zinc-F eluate significantly decreased green-stained bacterial cells, indicating live cells, compared with the control (no application). Human dentin coated with Zinc-F showed suppressed S. mutans and A. naeslundii biofilm formation. Additionally, Zinc-F eluate showed low cytotoxic effects in osteoblastic and fibroblastic cells. Therefore, our findings suggested that Zinc-F exhibits antibacterial and biocompatible properties through multiple-ion release.

  • Antibacterial tooth surface created by laser-assisted pseudo-biomineralization in a supersaturated solution.
    Ayako Oyane; Ikuko Sakamaki; Kenji Koga; Maki Nakamura; Kanako Shitomi; Hirofumi Miyaji
    Materials science & engineering. C, Materials for biological applications, 116, 111170, 111170, Nov. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A technique for implementing biocompatible and antibacterial functions to a targeted region on tooth surfaces has potential in dental treatments. We have recently demonstrated pseudo-biomineralization, i.e., the growth of an apatite layer on a human dentin substrate by a laser-assisted biomimetic (LAB) process, based on pulsed laser irradiation in a supersaturated CaP solution. In this study, pseudo-biomineralization was induced in the presence of fluoride ions using the LAB process in order to fabricate an antibacterial fluoride-incorporated apatite (FAp) layer on the dentin surface. After processing for 30 min, a micron-thick FAp layer was formed heterogeneously at the laser-irradiated solid-liquid interface via pseudo-biomineralization. A time-course study revealed that the LAB process first eliminated the pre-existing organic layer, while allowing fluoride incorporation into the dentin surface within 1 min. Within 5 min, FAp nanocrystals precipitated on the dentin surface. Within 30 min, these nanocrystals acquired a pillar-like structure that was weakly oriented in the direction normal to the substrate surface to form a dense micron-thick layer. This layer was integrated seamlessly with the underlying dentin without any apparent gaps. The FAp layer exhibited antibacterial activity against a major oral bacterium, Streptococcus mutans. The proposed LAB process is expected to be a useful new tool for tooth surface functionalization via facile and area-specific pseudo-biomineralization.
  • Technique for simple apatite coating on a dental resin composite with light-curing through a micro-rough apatite layer.
    Yasushi Hibino; Ayako Oyane; Kanako Shitomi; Hirofumi Miyaji
    Materials science & engineering. C, Materials for biological applications, 116, 111146, 111146, Nov. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Tooth root surfaces restored with dental resin composites exhibit inferior biocompatibility. The objective of this study was to develop a simple technique for coating apatite onto a resin composite to improve its surface biocompatibility. First, we fabricated a polymer film coated with a micro-rough apatite layer and pressed it (coating-side down) onto a viscous resin composite precursor. As a result of light-induced curing of the precursor through the overlaid film, the micro-rough apatite layer was integrated with the resin composite and, thus, transferred from the polymer film surface to the cured resin composite surface as a result of the difference in interfacial adhesion strength. The transferred apatite layer attached directly to the cured resin composite without any gaps at the microscopic level. The adhesion between the apatite layer and the cured resin composite was so strong that the layer was not peeled off even by a tape-detaching test. The flexural strength of the resulting apatite-coated resin composite was comparable to that of the clinically used resin composite while satisfying the ISO requirement for dental polymer-based restorative materials. Furthermore, the apatite-coated resin composite showed better cell compatibility than the uncoated resin composite. The present apatite coating technique is well suited for dental treatment because the coating is applied during a conventional light curing procedure through simple utilization of the apatite-coated polymer film in place of an uncoated film. The proposed technique represents a practical evolution in dental treatment using light-curing resin composites, although further in vitro and in vivo studies are needed.
  • Bone forming ability of recombinant human collagen peptide granules applied with β-tricalcium phosphate fine particles.
    Tomokazu Furihata; Hirofumi Miyaji; Erika Nishida; Akihito Kato; Saori Miyata; Kanako Shitomi; Kayoko Mayumi; Yukimi Kanemoto; Tsutomu Sugaya; Tsukasa Akasaka
    Journal of biomedical materials research. Part B, Applied biomaterials, 108, 7, 3033, 3044, 09 May 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Recombinant human collagen peptide, developed based on human collagen type I, contains an arginyl-glycyl-aspartic acid (RGD)-rich motif to enhance cell behavior and is anticipated as a xeno-free polymer material for use in tissue engineering. We fabricated granules containing recombinant human collagen peptide (RCP) applied with beta-tricalcium phosphate fine particles (RCP/β-TCP) as bone filling scaffold material and assessed the bone forming ability of RCP/β-TCP. Recombinant peptide was thermal crosslinked and freeze-dried to prepare RCP. An aqueous dispersion of β-TCP fine particles was added to RCP to obtain RCP/β-TCP. Subsequently, RCP/β-TCP were characterized using scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX), and cell culture assessments. Furthermore, RCP/β-TCP were implanted into rat cranial bone defects for radiographic and histological evaluations. In SEM and EDX analyses of RCP/β-TCP, β-TCP particles dose-dependently covered the surface of RCP. Cell culture tests showed that RCP/β-TCP remarkably promoted proliferation and mRNA expression of various genes, such as integrin β1 and osteogenic markers, of osteoblastic MC3T3-E1 cells. Histomorphometric assessment at 4 weeks showed that RCP/β-TCP significantly promoted new skull bone formation compared to RCP (p < 0.05) and control (no application) (p < 0.01). Accordingly, these findings suggest RCP/β-TCP possess bone forming capability and would be beneficial for bone tissue engineering therapy.
  • Comparative biological assessments of endodontic root canal sealer containing surface pre-reacted glass-ionomer (S-PRG) filler or silica filler.
    Hirofumi Miyaji; Kayoko Mayumi; Saori Miyata; Erika Nishida; Kanako Shitomi; Asako Hamamoto; Saori Tanaka; Tsukasa Akasaka
    Dental materials journal, 39, 2, 287, 294, 31 Mar. 2020, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, Surface pre-reacted glass-ionomer (S-PRG) filler releases several ions, such as fluoride, borate and strontium ions, to exert bioactive effects. We fabricated an endodontic root canal sealer containing S-PRG fillers (S-PRG sealer) and then evaluated the antibacterial and anti-inflammatory properties of S-PRG sealer compared with sealer containing conventional silica fillers (silica sealer). Antibacterial tests showed that S-PRG sealer significantly reduced the turbidity of Enterococcus faecalis compared with silica sealer. Implantation of S-PRG or silica sealer blocks in rat subcutaneous tissue showed that S-PRG sealer decreased the proinflammatory response compared with silica sealer at 10 days post-implantation. In addition, immunostaining revealed that infiltration of CD68- and peroxidase-positive cells around the S-PRG sealer was significantly lower than that in silica sealer. Therefore, it was suggested that S-PRG sealer exhibits antibacterial and anti-inflammatory effects.
  • Photodynamic inactivation of oral bacteria with silver nanoclusters/rose bengal nanocomposite.
    Kanako Shitomi; Hirofumi Miyaji; Saori Miyata; Tsutomu Sugaya; Natsumi Ushijima; Tsukasa Akasaka; Hideya Kawasaki
    Photodiagnosis and photodynamic therapy, 30, 101647, 101647, 02 Jan. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Antibacterial photodynamic therapy (a-PDT) is a promising anti-infective technique for generation of singlet oxygen (1O2) to target dental disease. However, conventional organic photosensitizers have some problems for clinical use in terms of cytotoxicity, quenching of a-PDT activity by self-dimerization, and the lack of long-term antibacterial effect. We herein propose silver nanoclusters/rose bengal nanocomposite (AgNCs/RB) as a novel photosensitizer with two primary antibacterial effects: (1) 1O2 generation by irradiated RB and (2) Ag+ ion release from AgNCs. AgNCs/RB irradiated with white light-emitting diode (LED) for a short irradiation time of 1 min significantly decreased the bacterial turbidity of Streptococcus mutans, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans (P < 0.05). In SEM, TEM and LIVE/DEAD staining images, photoexcited AgNCs/RB reduced S. mutans colonization, destroyed the cell membrane, and increased the number of dead cells. The antibacterial efficiency of photoexcited AgNCs/RB was greater than that of AgNCs or RB alone (P < 0.05), suggesting a synergistic effect of 1O2 and Ag + ions from photoexcited AgNCs/RB. By contrast, photoexcited AgNCs/RB did not affect WST-8 and LDH activities and morphology of NIH3T3 mammalian cells, indicating low cytotoxicity. Interestingly, the antibacterial activity of AgNCs/RB on S. mutans was maintained even after the cessation of LED irradiation, indicating a long-term antibacterial effect due to released Ag+ ions. The present AgNCs/RB photosensitizers provide effective synergistic antibacterial effects for dental a-PDT via 1O2 and Ag+ ions coupled with low cytotoxicity.
  • Laser-assisted biomineralization on human dentin for tooth surface functionalization.
    Ayako Oyane; Noriyuki Saito; Ikuko Sakamaki; Kenji Koga; Maki Nakamura; A Joseph Nathanael; Noriko Yoshizawa; Kanako Shitomi; Kayoko Mayumi; Hirofumi Miyaji
    Materials science & engineering. C, Materials for biological applications, 105, 110061, 110061, Dec. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, A technique for tooth surface modification with biocompatible calcium phosphate (CaP) has huge potential in dental applications. Recently, we achieved a facile and area-specific CaP coating on artificial materials by a laser-assisted biomimetic process (LAB process), which consists of pulsed laser irradiation in a supersaturated CaP solution. In this study, we induced the rapid biomineralization on the surface of human dentin by using the LAB process. A human dentin substrate was immersed in a supersaturated CaP solution, then its surface was irradiated with weak pulsed laser light for 30 min (LAB process). Ultrastructural analyses revealed that the pristine substrate had a demineralized collagenous layer on its surface due to the previous EDTA surface cleaning. After the LAB process, this collagenous layer disappeared and was replaced with a submicron-thick hydroxyapatite layer. We believe that the laser irradiation induced pseudo-biomineralization through the laser ablation of the collagenous layer, followed by CaP nucleation and growth at the dentin-liquid interface. The mineralized layer on the dentin substrate consisted of needle-like hydroxyapatite nanocrystals, whose c-axes were weakly oriented along the direction perpendicular to the substrate surface. This LAB process would offer a new tool enabling tooth surface modification and functionalization through the in situ pseudo-biomineralization.
  • Human Dentin Coated with Silver Nanoclusters Exhibits Antibacterial Activity against Streptococcus mutans
    Shitomi Kanako; Miyaji Hirofumi; Miyata Saori; Nishida Erika; Mayumi Kayoko; Sugaya Tsutomu; Kawasaki Hideya
    Nano Biomedicine, 11, 1, 21, 28, ナノ・バイオメディカル学会, Jun. 2019, [Peer-reviewed]
    English, 虫歯の病原菌であるStreptococcus mutansに対して審美的(象牙質変色予防)作用と抗菌的作用を持つ成分として、直径2nm未満の銀ナノクラスター(AgNC)を調製した。このAgNCはS.mutansの濁度と生存性を顕著に減少させるだけでなく、LIVE/DEAD染色法にて殺菌効果が認められた。このAgNCをヒト象牙質に適用すると、フッ化ジアミン銀を適用した場合と比べて象牙質の変色は認められず、AgNC-処理象牙質はS.mutansによるコロニー形成に対する阻害効果を示した。これらの結果から、AgNCは抗菌的・審美的基質として、歯科療法で有望と考えられた。
  • Rapid and area-specific coating of fluoride-incorporated apatite layers by a laser-assisted biomimetic process for tooth surface functionalization.
    A Joseph Nathanael; Ayako Oyane; Maki Nakamura; Moumita Mahanti; Kenji Koga; Kanako Shitomi; Hirofumi Miyaji
    Acta biomaterialia, 79, 148, 157, 01 Oct. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Surface functionalization of teeth with fluoride-incorporated apatite layers displays great potential in treatments and prevention of dental disorders. In this study, we used a sintered hydroxyapatite (sHA) substrate as a model material of teeth, and established a rapid and area-specific coating technique of fluoride-incorporated apatite layers by using a laser-assisted biomimetic (LAB) process. In this technique, a sHA substrate was irradiated on the surface with a Nd:YAG pulsed UV laser for 30 min in supersaturated calcium phosphate (CaP) solutions with various fluoride concentrations. The fluoride concentration in the CaP solution was varied to control morphology, crystalline structure, and fluoride content of the resulting layers. Without fluoride in the CaP solution, an octacalcium phosphate (OCP) layer with a flake-like structure was formed on the laser-irradiated surface of the substrate. The addition of fluoride (1000 µM and 3000 µM) to the CaP solution led to the formation of fluoride-incorporated apatite layers with an enamel-like needle-like nanostructure. The fluoride-incorporated apatite layers adhered firmly to the sHA surface and reduced acid dissolution of the sHA substrate by acting as a protective covering. Additionally, the layers released fluoride ions for more than 24 h, and exhibited antibacterial activity relative to a caries-causing bacterium, namely Streptococcus mutans. Thus, our LAB process can potentially act as a new tool for functionalization of tooth surfaces. STATEMENT OF SIGNIFICANCE: We used a sintered hydroxyapatite (sHA) substrate as a model material of teeth, and established a rapid and area-specific coating technique of fluoride-incorporated apatite layers on the sHA surface by using our laser-assisted biomimetic (LAB) process. In this process, pulsed laser was utilized to accelerate seeded crystal growth in supersaturated calcium phosphate solutions supplemented with NaF. The thus-fabricated fluoride-incorporated apatite layers consisted of enamel-like needle-like nanocrystals with c-axis orientation. These fluoride-incorporated apatite layers adhered firmly to the sHA surface, reduced acid dissolution of the sHA substrate by acting as a protective covering, and exhibited antibacterial activity against Streptococcus mutans through the fluoride release. Thus, our LAB process can potentially act as a new tool for functionalization of tooth surfaces.
  • Antibacterial Photocurable Acrylic Resin Coating Using a Conjugate between Silver Nanoclusters and Alkyl Quaternary Ammonium
    Chiaki Tominaga; Kanako Shitomi; Hirofumi Miyaji; Hideya Kawasaki
    ACS APPLIED NANO MATERIALS, 1, 9, 4809, 4818, Sep. 2018, [Peer-reviewed]
    English, Scientific journal
  • Bovine serum albumin-capped gold nanoclusters conjugating with methylene blue for efficient 1O2 generation via energy transfer.
    Masaki Yamamoto; Kanako Shitomi; Saori Miyata; Hirofumi Miyaji; Hiroyuki Aota; Hideya Kawasaki
    Journal of colloid and interface science, 510, 221, 227, 15 Jan. 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Bovine serum albumin (BSA)-capped gold nanoclusters (BSA-Au NCs) are attractive photosensitizers for efficient singlet oxygen 1O2 generation owing to their high-water solubility, low toxicity, and the broad absorption from UV to visible wavelengths, and the long lifetime of the electronic excitations (of the order of microseconds). However, the 1O2 generation efficiency of BSA-Au NCs is relatively low. In the present study, a conjugate of BSA-Au NCs and methylene blue (MB) (BSA-Au NC-MB conjugate) has been developed to improve 1O2 generation for antimicrobial photodynamic therapy (aPDT). The BSA-Au NC-MB conjugate demonstrated enhanced 1O2 generation compared to the case of BSA-Au NCs and effective aPDT ability under white-light LED illumination for only 1min due to the resonance energy transfer from the Au NCs to the MB in the conjugate. To the best of my knowledge, this is first report of Au NCs on the resonance energy transfer application for efficient 1O2 generation. Therefore, the BSA-Au NC-MB conjugate is a novel photosensitizer for 1O2 generation that shows great potential for aPDT, and the present study also develops a very simple strategy to fabricate albumin-based nanoparticles for PDT.
  • Near-infrared Irradiation and Graphene Oxide Film Fabricated on Dentin Surface Exhibit Photothermal and Antibacterial Effects
    Nagao Keishi; Miyaji Hirofumi; Nishida Erika; Akasaka Tsukasa; Miyata Saori; Shitomi Kanako; Mayumi Kayoko; Kato Akihito; Sugaya Tsutomu
    Journal of Oral Hygiene & Health, 6, 1, 231, 231, OMICS International, 10 Jan. 2018, [Peer-reviewed]
    English
  • Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog.
    Kohei Kawamoto; Hirofumi Miyaji; Erika Nishida; Saori Miyata; Akihito Kato; Akito Tateyama; Tomokazu Furihata; Kanako Shitomi; Toshihiko Iwanaga; Tsutomu Sugaya
    International journal of nanomedicine, 13, 2365, 2376, 2018, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Introduction: The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. Materials and methods: GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. Results: GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. Conclusion: The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy.
  • Bone Induction by α-tricalcium Phosphate Microparticle Emulsion Containing Simvastatin
    Tateyama Akito; Kato Akihito; Miyaji Hirofumi; Nishida Erika; Iwasaki Yasuhiko; Fujii Syuji; Kawamoto Kohei; Shitomi Kanako; Furihata Tomokazu; Mayumi Kayoko; Sugaya Tsutomu
    Nano Biomedicine, 9, 2, 69, 76, ナノ・バイオメディカル学会, Dec. 2017, [Peer-reviewed]
    English, 骨移植材の分解性と操作性を改善するため、α型リン酸トリカルシウム(α-TCP)骨ペーストを基にした水-オイル懸濁液を調製した。親油性の抗高脂血症薬であるシンバスタチン(SIM)には骨形成促進作用が認められているため、SIM含有α-TCP骨ペーストを用いてラットの頭蓋骨欠損に対する骨形成効果を評価した。骨ペーストは固化後に多孔性構造とヒドロキシアパタイトの生成を示すので、頭蓋骨欠損部への移植後にX線画像解析と組織学的検査を行った。骨ペーストのSIM含有量は0、0.01、0.1および1mgとし、無SIMの対照骨ペーストと比較した。その結果、骨ペースト移植後に新たな骨形成が認められ、特に0.1mg SIM群では対照群に比べて骨体積が有意に促進され、術後4週では骨欠損部に骨ペースト残渣は見られなかった。以上より、SIM含有α-TCP骨ペーストは分解性であり、骨組織工学にとって有用であることが示唆された。
  • Antibacterial and cytotoxic effects of photoexcited Au clusters via blue high-power or white low-power light emitting diode irradiation
    Miyata Saori; Miyaji Hirofumi; Kawasaki Hideya; Nishida Erika; Shitomi Kanako; Akasaka Tsukasa; Tanaka Saori; Iizuka Tadashi; Sugaya Tsutomu
    Biology, Engineering and Medicine, 2, 4, Open Access Text, Oct. 2017, [Peer-reviewed]
    English, The development of photosensitizers and light sources has enabled the use of antimicrobial photodynamic therapy (aPDT) in various dental therapies. In the presentstudy, we compared the antibacterial and cytotoxic effects of Au clusters photoexcited by blue and white LED irradiation. We fabricated novel photosensitizers,captopril-protected gold (Capt-Au) clusters and lysozyme-stabilized gold (Lyz-Au) clusters, for aPDT. Au clusters were then photoexcited by two kinds of lightsources, blue high-power and white low-power light-emitting diodes (LEDs). Since white LED contains a wide spectrum of light (400–750 nm), white LED wouldbe relevant for aPDT even if using a low-power source.The turbidity and viability of Streptococcus mutans were assessed following application of Capt-Au clusters (500 μg/mL) or Lyz-Au clusters (1,000 μg/mL) photoexcitedby a blue high-power LED (1,000 mW/cm2) or white low-power LED (80 mW/cm2). In addition, the cytotoxicity of Au clusters and LED irradiation was evaluatedin NIH3T3 and MC3T3-E1 cells.Au clusters photoexcited by the white low-power LED equally decreased the turbidity and viability of S. mutans compared with blue high-power LED. However,Au clusters photoexcited by white LED irradiation caused decreased cytotoxicity in mammalian cells compared with those photoexcited by blue LED irradiation. Inconclusion, white LEDs possess biosafe properties for aPDT using Au clusters.
■ Other Activities and Achievements
■ Syllabus
  • フロンティア基礎科目, 2024年, 学士課程, 歯学部
■ Research Themes
  • レーザーで軟化象牙質をアパタイトに置換する－根面う蝕治療法の新規開発
    科学研究費助成事業
    01 Apr. 2025 - 31 Mar. 2028
    宮治 裕史; 大矢根 綾子; 松田 康裕; 西田 絵利香; 蔀 佳奈子
    日本学術振興会, 基盤研究(B), 北海道大学, 25K02808
  • LABプロセスを用いたインプラント周囲炎の革新的再生治療法創出
    科学研究費助成事業
    01 Apr. 2025 - 31 Mar. 2028
    西田 絵利香; 宮治 裕史; 蔀 佳奈子; 黒嶋 伸一郎; 大矢根 綾子; 島袋 将弥
    日本学術振興会, 基盤研究(C), 北海道大学, 25K13061
  • Development of antibacterial sonodynamic therapy for periodontal disease
    Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up
    11 Sep. 2020 - 31 Mar. 2022
    蔀 佳奈子
    歯周病は人が歯を失う原因となる罹患率の高い疾患である。歯周病に罹患し形成された歯周ポケット内には様々な細菌が存在しバイオフィルムを形成しており、このバイオフィルム除去が歯周病治療に不可欠である。
    音響力学療法(Sonodynamic Therapy: SDT）は音増感剤に超音波を照射することで生成する一重項酸素（強力な酸化力をもつ活性酸素）を利用したがん治療法として注目されている。一重項酸素は殺菌作用があることでも知られ、歯科用超音波装置との併用によるバイオフィルム除去作用が期待できる。しかし、SDTの歯周病治療への効果については報告されていない。本研究では金属ナノクラスターを音増感剤として使用し、歯科用超音波装置との併用による口腔内細菌への抗菌効果を明らかにする。
    金ナノクラスターは光刺激によって高効率に一重項酸素を発生することはすでに知られており、超音波刺激でも同様に一重項酸素を発生することが近年注目されている。そこで歯科用超音波装置による超音波照射時の一重項酸素生成を一重項酸素検出プローブを用いた紫外可視スペクトルで同定、定量化する。超音波刺激で生成した一重項酸素および音増感剤として使用する金ナノクラスターの殺菌効果と生体への安全性を口腔内細菌及び線維芽細胞を用いてin vitroで検証する。殺菌効果の評価には歯周病原細菌であるA naeslundii, P intermedia，P gingivalisを用いる。生体安全性の評価にはNIH3T3細胞を用いることとする。さらに殺菌効果の機序を知るため、SDT後の細菌中の金ナノクラスターの局在をTEM観察
    で調べる。
    Japan Society for the Promotion of Science, Grant-in-Aid for Research Activity Start-up, Health Sciences University of Hokkaido, 20K23089