Updated on 2025/01/10

Information

 

写真a

 
HAYASHI KOICHIRO
 
Organization
Faculty of Dental Science Department of Dental Science Associate Professor
School of Dentistry Department of Dentistry(Concurrent)
Graduate School of Dental Science (Concurrent)
Graduate School of Dental Science Department of Dental Science(Concurrent)
Title
Associate Professor
Profile
硬・軟組織再生やナノ医療等の生体材料に関する研究及び教育(大学院)。歯科理工学に関する教育(学部)。
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Research Areas

  • Life Science / Biomaterials

  • Nanotechnology/Materials / Nanomaterials

  • Nanotechnology/Materials / Nanobioscience

Research History

  • Kyushu University Faculty of Dental Science Department of Dental Science  Associate Professor 

    2018.4 - Present

  • Kyushu University 歯学研究院 歯学部門   

    2017.9 - 2018.3

  • Nagoya University 未来材料・システム研究所 Assistant Professor 

    2014.5 - 2017.8

  • The University of Tokushima 大学院医歯薬学研究部 医科学部門 Assistant Professor 

    2010.4 - 2014.5

  • Nagoya University 大学院工学研究科 日本学術振興会 特別研究員 (DC2) 

    2009.4 - 2010.3

Research Interests・Research Keywords

  • Research theme: Biomaterials, Scaffolds, Nanomedicine, Theranostics

    Keyword: Biomaterials, Scaffolds, Honeycomb, Nanomedicine, Theranostics

    Research period: 2004.4

Awards

  • 2022 Best Research Award

    2022   九州大学  

    Koichiro Hayashi

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  • 九州大学歯学優秀研究者賞 IF部門

    2021.2   九州大学   ハニカムスキャフォールドの気孔構造と骨再生能との関係性解明

  • 第75回日本歯科理工学会学術講演会企業賞

    2020.4   日本歯科理工学会   炭酸アパタイトハニカムスキャホールドの骨誘導能評価

  • 第32回日本DDS学会学術集会優秀発表賞

    2016.7   日本DDS学会   赤血球様粒子の作製と体内動態の解明

  • 東海化学工業会賞

    2016.3   東海化学工業   多機能ハイブリッドナノ粒子の合成とバイオメディカル応用

  • 日本セラミックス協会進歩賞

    2015.11   日本セラミックス協会   診断治療機能を有する機能性セラミックスナノ粒子材料の開発

  • 日本セラミックス協会第28回秋季シンポジウム 特定セッション 「生体との調和を生み出すセラミックスの開発と評価」 若手優秀発表賞

    2015.9   日本セラミックス協会   交流磁場応答性スマートコア-シェルナノ粒子の合成と磁気温熱化学療法への応用

  • 徳島大学若手研究者学長賞

    2013.11   徳島大学   機能性ナノ粒子を用いた診断及び治療

  • ナノ学会第11回大会 Young best presentation award

    2013.6   ナノ学会   超常磁性ナノ粒子クラスターの合成とMRI/ハイパーサーミアセラノスティクスへの応用

  • 岡奨学賞

    2013.3   機能性ナノ粒子を用いた癌の早期診断及び非侵襲治療法の開発

  • 日本セラミックス協会第25回秋季シンポジウム優秀発表賞

    2012.9   日本セラミックス協会   鉄-コバルト錯体を用いたコバルトフェライト/高分子ハイブリッドナノ粒子のin situ合成と磁気ハイパーサーミアへの応用

  • 徳島大学 ベスト・ティーチャー・オブ・ザ・イヤー

    2012.3   徳島大学  

  • 愛知県若手研究者奨励事業「わかしゃち奨励賞」

    2008.2   愛知県   診断機能を有するがん温熱治療用新規磁性ナノ材料の開発

  • 名古屋大学学術奨励賞受賞

    2007.7   名古屋大学   次世代の高速・大容量光情報通信に適用可能な透明磁性自立膜の開発に関する研究

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Papers

  • Wood-Derived Hydrogels for Osteochondral Defect Repair Reviewed

    Koichiro Hayashi, Tatsuya Tokumaru, Keigo Shibahara, Ahmad Nazir Taleb Alashkar, Cheng Zhang, Ryo Kishida, Yasuharu Nakashima, Kunio Ishikawa

    ACS Nano   2025.1

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  • Wood-Derived Hydrogels for Osteochondral Defect Repair Reviewed

    Koichiro Hayashi, Tatsuya Tokumaru, Keigo Shibahara, Ahmad Nazir Taleb Alashkar, Cheng Zhang, Ryo Kishida, Yasuharu Nakashima, Kunio Ishikawa

    ACS Nano   2025.1

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  • Migration Prevention of Carbonate Apatite Granules Through Crystal Interlocking Driven by Bassanite-to-Gypsum Transformation on Granule Surface Invited Reviewed

    Luis Miguel Torres Escalante, Koichiro Hayashi, Kunio Ishikawa

    Applied Sciences   14 ( 23 )   2024.12   eISSN:2076-3417

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Applied Sciences (Switzerland)  

    Featured Application: This study provides an innovative approach to prevent the migration of carbonate apatite (CAp) granules during implantation. The proposed method combines the setting properties of calcium sulfate hemihydrate (CSH) with CAp granules, enabling their use as a stable, porous scaffold for bone regeneration. Granular bone substitutes are commonly used in dental treatments owing to their adaptability to irregular bone defects. However, granule migration during and after implantation poses a significant challenge, impairing bone regeneration. This study addresses this issue by setting carbonate apatite (CAp) granules using crystal interlocking owing to the bassanite (calcium sulfate hemihydrate (CSH))-to-gypsum (calcium sulfate dihydrate (CSD)) transformation on the granule surface. CAp granules were mixed with CSH slurry (water/CSH ratio of 0.4) at varying CSH/CAp ratios of 0.33, 0.43, 0.54, 0.67, and 0.82. At all of these mixing ratios, needle-shaped CSD crystals formed on the CAp granule surface, and the CSD crystals interlocked with each other; consequently, CAp granules were set. As the CSH/CAp ratio increased from 0.33 to 0.82, the CSD crystal length increased from 6.58 to 6.79 μm, while the setting time decreased from 30.3 to 15.5 min. Although the porosity of the set CAp granules decreased with an increase in the CSH/CAp ratio, the set granules maintained intergranular spaces of 77.3 μm at a CSH/CAp ratio of 0.82 conducive to cellular infiltration. After immersion in saline for six days, the set CAp granules at a CSH/CAp ratio of 0.82 maintained their original shape, demonstrating enhanced stability compared to lower CSH/CAp ratios where partial or complete collapse occurred. The porosity and specific surface area increased to 59.9% and 3.66 m2/g, respectively, and the intergranular spaces increased to 176.4 μm. Therefore, mixing the CAp granules with CSH at a ratio of 0.82 may prevent granule migration during and after implantation. Moreover, the CSD component of the granules is likely to resorb more rapidly than the CAp component in vivo, promoting porosity in the set granules and facilitating efficient bone replacement.

    DOI: 10.3390/app142311261

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  • Carbonate Apatite Honeycomb Scaffold-Based Drug Delivery System for Repairing Osteoporotic Bone Defects Reviewed

    Koichiro Hayashi, Cheng Zhang, Ahmad Nazir Taleb Alashkar, Kunio Ishikawa

    ACS Applied Materials & Interfaces   16 ( 35 )   45956 - 45968   2024.8   ISSN:1944-8244 eISSN:1944-8252

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    Osteoporotic bone defects are difficult to repair in elderly patients. This study aimed to repair osteoporotic bone defects using a combination of bone tissue engineering (BTE) and drug delivery systems (DDS). Herein, honeycomb granules (HCGs) composed of carbonate apatite microspheres were fabricated as BTE scaffolds. Each HCG possesses hexagonal macropores and abundant interconnected micropores between the microspheres. Owing to these multiscale interconnected pores, HCGs can readily contain antibodies against sclerostin (Scl), which causes imbalances in bone homeostasis. Anti-Scl antibody-loaded HCGs (Scl-Ab-HCGs) regulate the release of Scl-Abs in response to the pH of the osteoporotic environment. In ovariectomized rabbit osteoporotic femurs, HCG monotherapy forms new bone with less osteocyte damage (fewer empty bone lacunae) and fewer osteoclasts than osteoporotic bone; however, it is insufficient to prevent receptor activator of nuclear factor-kappa B ligand (RANKL) overexpression. Consequently, HCG monotherapy restores bone quantity better than no treatment but not to normal levels. In contrast, new bone tissue formed by Scl-Ab-HCG-based DDS predominantly expresses osteocalcin rather than RANKL, similar to normal bone, and shows a similar osteocyte apoptosis level, bone quantity, and osteoclast number as normal bone. Thus, Scl-Ab-HCG-based DDS is a promising approach for osteoporotic bone defect repair.

    DOI: 10.1021/acsami.4c08047

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  • Silver phosphate-modified carbonate apatite honeycomb scaffolds for anti-infective and pigmentation-free bone tissue engineering Reviewed

    Koichiro Hayashi, Masaya Shimabukuro, Cheng Zhang, Ahmad Nazir Taleb Alashkar, Ryo Kishida, Akira Tsuchiya, Kunio Ishikawa

    Materials Today Bio   27   101161 - 101161   2024.8   ISSN:2590-0064

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    Bone regeneration using synthetic materials has a high rate of surgical site infection, resulting in severe pain for patients and often requiring revision surgery. We propose Ag3PO4-based surface modification and structural control of scaffolds for preventing infections in bone regeneration. We demonstrated the differences in toxicity and antibacterial activity between in vitro and in vivo studies and determined the optimal silver content in terms of overall anti-infection effects, bone regeneration, toxicity, and pigmentation. A honeycomb structure comprising osteoconductive and resorbable carbonate apatite (CAp) was used as the base scaffold. CAp in the scaffold surface was partially replaced with different concentrations of Ag3PO4 via controlled dissolution-precipitation reactions in an AgNO3 solution. Both bone regeneration and infection prevention were achieved at 860–2300 ppm of silver. Despite the absence of Ag3PO4, honeycomb scaffolds were less susceptible to infection, even under conditions where infection occurs in clinically used three-dimensional porous scaffolds. Regardless of in vitro cytotoxicity at >5200 ppm of silver, increasing the silver content to 21,000 ppm did not adversely affect in vivo bone formation and scaffold resorption or cause acute systemic toxicity. Rather, bone formation was enhanced with 5200 ppm of silver. However, pigmentation was observed at that concentration. Hence, we concluded that the optimal silver concentration range is 860–2300 ppm for anti-infective and pigmentation-free bone regeneration. Bone regeneration was achieved via surface modification, resulting in the rapid release of silver ions immediately after implantation, followed by gradual release over several months. The scaffold structure may also aid in preventing bacterial growth within the scaffolds.

    DOI: 10.1016/j.mtbio.2024.101161

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  • Hematopoietic Function Restoration by Transplanting Bone Marrow Niches In Vivo Engineered Using Carbonate Apatite Honeycomb Bioreactors Reviewed

    Koichiro Hayashi, Ryo Kishida, Akira Tsuchiya, Kunio Ishikawa

    Small Structures   5 ( 10 )   2400065   2024.6   ISSN:2688-4062 eISSN:2688-4062

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Hematopoietic stem cell (HSC) transplantation is used to treat blood and immunodeficient diseases. HSC expansion techniques must be developed to prevent complications and ensure reliable therapeutic efficacy. Hence, several studies have attempted in vitro expansion of HSCs using scaffolds but failed to mimic the diverse and complex nature of HSC environments. Herein, an artificial HSC microenvironment, bone marrow (BM) niches is created, through in vivo engineering using carbonate apatite honeycomb scaffolds and the potential of these scaffolds in restoring lost hematopoietic function and immunity is investigated. BM niches are generated in every honeycomb channel, wherein HSCs are gradually aggregated. Compared to the actual BM, the scaffolds exhibit a 9.9‐ and 78‐fold increase in the number of stored CD45<sup>−</sup> CD34<sup>+</sup> side scatter<sup>low</sup> cells that are mainly considered HSCs at 8 and 12 weeks, respectively. The transplantation of the honeycomb scaffold containing HSCs and BM niches into immunocompromised mice increases peripheral blood chimerism and restores hematopoietic function and the number of immunocytes (monocytes and lymphocytes) to normal levels. This study contributes to the development of efficient HSC transplantation techniques. Additionally, in vivo‐engineered integrated tissues using honeycomb scaffolds can be used to elucidate the interplay between the BM niches and resident cells.

    DOI: 10.1002/sstr.202400065

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  • Transformable Carbonate Apatite Chains as a Novel Type of Bone Graft Reviewed International journal

    @Koichiro Hayashi, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    Advanced Healthcare Materials   13 ( 12 )   2303245   2024.1   ISSN:2192-2640 eISSN:2192-2659

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Abstract

    The aging global population is generating an ever‐increasing demand for bone regeneration. Various materials, including blocks, granules, and sponges, are developed for bone regeneration. However, blocks require troublesome shaping and exhibit poor bone‐defect conformities; granules migrate into the surrounding tissues during and after filling of the defect, causing handling difficulties and complications; and sponges contain polymers that are subject to religious restrictions, lack osteoconductivity, and may cause inflammation and allergies. Herein, carbonate apatite chains that overcome the limitations of conventional materials are presented. Although carbonate apatite granules migrate, causing inflammation and ectopic calcification, the chains remain in the defects without causing any complications. The chains conform to the defect shape and transform into 3D porous structures, resulting in faster bone regeneration than that observed using granules. Thus, these findings indicate that even traditional calcium phosphates materials can be converted to state‐of‐the‐art materials via shape control.

    DOI: 10.1002/adhm.202303245

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  • Superiority of Triply Periodic Minimal Surface Gyroid Structure to Strut-Based Grid Structure in Both Strength and Bone Regeneration Reviewed International journal

    @Koichiro Hayashi, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    ACS Applied Materials & Interfaces   15 ( 29 )   34570 - 34577   2023.7   ISSN:1944-8244 eISSN:1944-8252

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    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:American Chemical Society (ACS)  

    The aging population has rapidly driven the demand for bone regeneration. The pore structure of a scaffold is a critical factor that affects its mechanical strength and bone regeneration. Triply periodic minimal surface gyroid structures similar to the trabecular bone structure are considered superior to strut-based lattice structures (e.g., grids) in terms of bone regeneration. However, at this stage, this is only a hypothesis and is not supported by evidence. In this study, we experimentally validated this hypothesis by comparing gyroid and grid scaffolds composed of carbonate apatite. The gyroid scaffolds possessed compressive strength approximately 1.6-fold higher than that of the grid scaffolds because the gyroid structure prevented stress concentration, whereas the grid structure could not. The porosity of gyroid scaffolds was higher than that of the grid scaffolds; however, porosity and compressive strength generally have a trade-off relationship. Moreover, the gyroid scaffolds formed more than twice the amount of bone as grid scaffolds in a critical-sized bone defect in rabbit femur condyles. This favorable bone regeneration using gyroid scaffolds was attributed to the high permeability (i.e., larger volume of macropores or porosity) and curvature profile of the gyroid structure. Thus, this study validated the conventional hypothesis using in vivo experiments and revealed factors that led to this hypothetical outcome. The findings of this study are expected to contribute to the development of scaffolds that can achieve early bone regeneration without sacrificing the mechanical strength.

    DOI: 10.1021/acsami.3c06263

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  • Effects of Scaffold Shape on Bone Regeneration: Tiny Shape Differences Affect the Entire System Reviewed International journal

    @Koichiro Hayashi, @Toshiki Yanagisawa, @Ryo Kishida, @Kunio Ishikawa

    ACS Nano   16 ( 8 )   11755 - 11768   2022.7   ISSN:1936-0851 eISSN:1936-086X

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    Although studies on scaffolds for tissue generation have mainly focused on the chemical composition and pore structure, the effects of scaffold shape have been overlooked. Scaffold shape determines the scaffold surface area (SA) at the single-scaffold level (i.e., microscopic effects), although it also affects the amount of interscaffold space in the tissue defect at the whole-system level (i.e., macroscopic effects). To clarify these microscopic and macroscopic effects, this study reports the osteogenesis abilities of three types of carbonate apatite granular scaffolds with different shapes, namely, irregularly shaped dense granules (DGs) and two types of honeycomb granules (HCGs) with seven hexagonal channels (∼255 μm in length between opposite sides). The HCGs possessed either 12 protuberances (∼75 μm in length) or no protuberances. Protuberances increased the SA of each granule by 3.24 mm2 while also widening interscaffold spaces and increasing the space percentage in the defect by ∼7.6%. Interscaffold spaces were lower in DGs than HCGs. On DGs, new bone formed only on the surface, whereas on HCGs, bone simultaneously formed on the surface and in intrascaffold channels. Interestingly, HCGs without protuberances formed approximately 30% more new bone than those with protuberances. Thus, even tiny protuberances on the scaffold surface can affect the percentage of interscaffold space, thereby exerting dominant effects on osteogenesis. Our findings demonstrate that bone regeneration can be improved by considering macroscopic shape effects beyond the microscopic effects of the scaffold.

    DOI: 10.1021/acsnano.2c03776

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  • Antibacterial Honeycomb Scaffolds for Achieving Infection Prevention and Bone Regeneration Reviewed International journal

    @Koichiro Hayashi, @Masaya Shimabukuro, @Kunio Ishikawa

    ACS Applied Materials & Interfaces   14 ( 3 )   3762 - 3772   2022.1   ISSN:1944-8244 eISSN:1944-8252

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    Surgical site infection (SSI) is a severe complication associated with orthopedic bone reconstruction. For both infection prevention and bone regeneration, the framework surface of osteoconductive and bioresorbable scaffolds must be locally modified by minimum antibacterial substances, without sacrificing the osteoconductivity of the scaffold framework. In this study, we fabricated antibacterial honeycomb scaffolds by replacing carbonate apatite, which is the main component of the scaffold, with silver phosphate locally on the scaffold surface via dissolution–precipitation reactions. When the silver content was 9.9 × 10–4 wt %, the honeycomb scaffolds showed antibacterial activity without cytotoxicity and allowed cell proliferation, differentiation, and mineralization. Furthermore, the antibacterial honeycomb scaffolds perfectly prevented bacterial infection in vivo in the presence of methicillin-resistant Staphylococcus aureus, formed new bone at 2 weeks after surgery, and were gradually replaced with a new bone. Thus, the antibacterial honeycomb scaffolds achieved both infection prevention and bone regeneration. In contrast, severe infection symptoms, including abscess formation, osteolytic lesions, and inflammation, occurred 2 weeks after surgery when honeycomb scaffolds without silver phosphate modification were implanted. Nevertheless, the unmodified honeycomb scaffolds eliminated bacteria and necrotic bone through their scaffold channels, resulting in symptom improvement and bone formation. These results suggest that the honeycomb structure is inherently effective in hindering bacterial growth. This novel insight may contribute to the development of antibacterial scaffolds. Moreover, our modification method is useful for providing antibacterial activity to various biomaterials.

    DOI: 10.1021/acsami.1c20204

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  • Controlling the pore size of carbonate apatite honeycomb scaffolds enhances orientation and strength of regenerated bone Reviewed

    Keigo Shibahara, Koichiro Hayashi, Yasuharu Nakashima, Kunio Ishikawa

    Biomaterials Advances   166   214026 - 214026   2025.1   ISSN:2772-9508 eISSN:2772-9508

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    To restore functions of long bones and avoid reconstruction failure, segmental defects should be quickly repaired using abundant amounts of regenerated bone with high mechanical strength and orientation along the bone axis. Although both bone volume and bone matrix orientation are important for faster restoration of long bones with segmental defects, researchers have primarily focused on the former. Artificial bone scaffolds with uniaxial channels, (e.g., honeycomb (HC) scaffolds), are considered adequate for regenerating bone oriented along the bone axis. The channel size may affect the orientation, amount, and strength of the regenerated bone. In this study, we investigated the effects of channel size in carbonate apatite HC scaffolds on the orientation of bones regenerated in segmental bone defects and determined the adequate channel size. Carbonate apatite HC scaffolds, with different channel sizes (350, 550, 730, and 890 μm in length on the side of the square aperture), were fabricated by extrusion molding of a mixture of calcium carbonate and organic binder, debinding, and subsequent phosphatization to convert the composition from calcium carbonate to carbonate apatite. No significant difference in the amounts of regenerated bones was observed for different channel sizes. However, bone along the bone axis was formed in the channels ≤550 μm in size but not in channels ≥730 μm. The HC scaffolds with a channel size of 350 μm regenerated bone with higher bending strength than those with a channel size of 890 μm. However, bone regenerated with the HC scaffolds having channel sizes of 350, 550, and 730 μm showed equal bending strength. Thus, the adequate channel size for fast regeneration of high-strength bone, oriented to the bone axis, is ≤730 μm. To the best of our knowledge, this is the first study to report the effect of channel size on bone orientation and strength. The findings of this study are relevant to the fast repair of segmental bone defects.

    DOI: 10.1016/j.bioadv.2024.214026

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  • Bone augmentation using bioresorbable mesh domes containing bone graft granules Reviewed

    Toshiki Yanagisawa, Koichiro Hayashi, Kunio Ishikawa

    Journal of Materials Science: Materials in Medicine   35 ( 1 )   61   2024.10   ISSN:0957-4530 eISSN:1573-4838

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Bone graft granules are valuable tools for ridge area bone grafting owing to their ease of manipulation and interconnected porous structure. Guided bone regeneration (GBR) using barrier membranes is commonly used for alveolar ridge augmentation; however, the surgical procedures are technically complicated. In this study, we fabricated bioresorbable mesh domes (BMDs) using two types of Vicryl mesh (woven and knitted types) containing carbonate apatite granules. BMD samples were prepared in three groups: upper sides made from the woven type (UW) and lower sides made from the woven type (LW) (the UW/LW group), upper sides made from the woven type (UW) and lower sides made from the knitted type (LK) (the UW/LK group), and upper sides made from the knitted type (UK) and lower sides made from the knitted type (LK) (the UK/LK group). The samples were subsequently implanted into rabbit calvaria, and radiomorphometric and histological analyses were conducted. The UK/LK group exhibited enhanced appositional bone formation because the knitted mesh on the skin side prevented the infiltration of a substantial amount of fibrous tissue. This increase in bone formation could be attributed to the interaction between granules and osteoprogenitors that pass through the mesh from the host bone. Conversely, the UW/LW and UW/LK groups presented limited appositional bone formation. Compared with knitted mesh, woven mesh might tend to be absorbed over a short span, allowing fibrous tissue invasion and inhibiting new bone formation. Additionally, BMDs could retain granules in a targeted location and avoid displacement of the granules to unintended locations. Graphical Abstract: (Figure presented.)

    DOI: 10.1007/s10856-024-06833-8

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    Other Link: https://link.springer.com/article/10.1007/s10856-024-06833-8/fulltext.html

  • Fabrication of magnesium-doped biphasic calcium phosphate granules with sea urchin spine-derived porous structure Reviewed

    Muhammad Amir Jamilludin, Koichiro Hayashi, Yusril Yusuf, Kunio Ishikawa

    Ceramics International   50 ( 14 )   25988 - 25999   2024.7   ISSN:0272-8842 eISSN:1873-3956

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    In bone regeneration, synthetic materials are required to replace autogenous bone grafts. The shape, composition, surface, and porous structure of the material are key factors in bone formation and material resorption. In this study, we describe the fabrication of Mg-doped biphasic calcium phosphate (Mg-BCP) granules comprising hydroxyapatite (HAp) and beta-tricalcium phosphate (β-TCP) by exploiting the structural and chemical characteristics of sea urchin spines. The Mg-BCP granules were cylinders with a 1.2–1.8 mm diameter and height of 1.4–1.7 mm. The β-TCP/HAp ratio and Mg content in the Mg-BCP granules were controlled within the ranges of 0.36–0.45 and 2.40–6.21 mol%, respectively. Controlling the β-TCP/HAp ratio and Mg content may contribute to controlling the material resorption rate and promoting osteogenesis and angiogenesis. The Mg-BCP granules maintained the structural characteristics of the sea urchin spines. The granules comprised radial wedges termed septa, and a meshwork termed stereom. The interseptal gaps, or micropores, decreased from the granular exterior (24–29 μm) to the interior (14–28 μm). The septa in the outermost layer provide concavities on the sides of the cylindrical granules. The stereom meshworks in the core and outer layers involved micropores in the ranges of 3–15 and 3–10 μm, respectively. These multiscale pores and surface undulations may improve cell penetration and attachment, bodily fluid permeability, and protein adsorption. The compressive strengths of the Mg-BCP granules were in the range of 45.2–46.1 MPa, which are useful as bone grafts. Due to their rounded shapes, the Mg-BCP granules filled a mold more densely than the clinically used and irregularly shaped granules. These findings demonstrated that Mg-BCP granules are promising materials for bone regeneration.

    DOI: 10.1016/j.ceramint.2024.04.341

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  • In vivo trial of bioresorbable mesh cages contained bone graft granules in rabbit femoral bone defects Reviewed

    Toshiki Yanagisawa, Koichiro Hayashi, Akira Tsuchiya, Ryo Kishida, Kunio Ishikawa

    Scientific Reports   14 ( 1 )   12449   2024.5   ISSN:2045-2322 eISSN:2045-2322

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    Abstract

    Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.

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    Other Link: https://www.nature.com/articles/s41598-024-63067-y

  • Roles of Pore Architecture of Artificial Bone Grafts in Invasion Competition between Bone and Fibrous Tissue and Orientation of Regenerated Bone Invited Reviewed International journal

    #Keigo Shibahara, @Koichiro Hayashi, @Yasuharu Nakashima, @Kunio Ishikawa

    International Journal of Bioprinting   10 ( 2 )   2323 - 2323   2024.3   ISSN:2424-7723 eISSN:2424-8002

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    &amp;nbsp;In the reconstruction of bone defects close to soft tissue, preventing the invasion of fibrous tissue into the bone defect is key to successful bone reconstruction. In this study, we clarified the effects of the pore architecture of artificial bone grafts on the penetration of bone and fibrous tissue, and the orientation of regenerated bone. Carbonate apatite grafts with uniaxial pores along the long- (L-graft) or short-axis (S-graft) direction of the graft and biaxial pores along the long- and short-axes (LS-graft) were used. These grafts were implanted in bone defects created by rabbit ulnae amputation. The pores of the L-, S-, and LS-grafts opened into the bone stumps, muscles, and bone stumps and muscles together, respectively. In the L-graft, the graft pores developed bone from the bone stump to the graft center, while preventing excessive invasion of fibrous tissue. In S- and LS-grafts, the graft pores along the short axis allowed the invasion of fibrous tissue into the grafts. Consequently, although the bone grew to the edge regions in these grafts, further bone ingrowth was inhibited by the fibrous tissue. Furthermore, the pore architecture of the grafts affected the orientation of the regenerated bone. The degree of orientation of the bone formed in the L- and S-grafts was 1.6-fold higher than that formed in the LS-grafts. Thus, controlling the pore architecture allowed the growth of bone to predominate over that of fibrous tissue and induced the formation of bone with an ordered orientation

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  • Lamellar Septa-like Structured Carbonate Apatite Scaffolds with Layer-by-Layer Fracture Behavior for Bone Regeneration Invited Reviewed International journal

    #Ahmad Nazir Taleb Alashkar, @Koichiro Hayashi, @Kunio Ishikawa

    Biomimetics   9 ( 2 )   112 - 112   2024.2   eISSN:2313-7673

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    Generally, ceramics are brittle, and porosity is inversely correlated with strength, which is one of the challenges of ceramic scaffolds. Here, we demonstrate that lamellar septum-like carbonate apatite scaffolds have the potential to overcome these challenges. They were fabricated by exploiting the cellular structure of the cuttlebone, removing the organic components from the cuttlebone, and performing hydrothermal treatment. Scanning electron microscopy revealed that the scaffolds had a cellular structure with walls between lamellar septa. The interwall and interseptal sizes were 80–180 and 300–500 μm, respectively. The size of the region enclosed by the walls and septa coincided with the macropore size detected by mercury intrusion porosimetry. Although the scaffold porosity was extremely high (93.2%), the scaffold could be handled without disintegration. The compressive stress–strain curve demonstrated that the scaffolds showed layer-by-layer fracture behavior, which seemed beneficial for avoiding catastrophic failure under impact. When the scaffolds were implanted into rabbit femurs, new bone and blood vessels formed within the scaffold cells at 4 weeks. At 12 weeks, the scaffolds were almost entirely replaced with new bone. Thus, the lamellar septum-like cellular-structured carbonate apatite is a promising scaffold for achieving early bone regeneration and compression resistance.

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  • Carbonate Apatite Honeycomb Materials that Serve as Hematopoietic Stem Cell Niches and Restore Hematopoietic Function Invited Reviewed

    Koichiro Hayashi

    バイオマテリアル-生体材料-   42 ( 1 )   2024.1

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  • Effects of Space Dimensionality within Scaffold for Bone Regeneration with Large and Oriented Blood Vessels Invited Reviewed International journal

    @Koichiro Hayashi, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    Materials   16 ( 24 )   7518   2023.12   ISSN:1996-1944 eISSN:1996-1944

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    The internal structure of the scaffolds is a key factor for bone regeneration. In this study, we focused on the space dimensionality within the scaffold that may control cell migration and evaluated the effects on the size and orientation of blood vessels and the amount of bone formation in the scaffold. The carbonate apatite scaffolds with intrascaffold space allowing one-dimensional (1D), two-dimensional (2D), or three-dimensional (3D) cell migration were fabricated by 3D printing. These scaffolds had the same space size, i.e., distances between the struts (~300 µm). The scaffolds were implanted into the medial condyle of rabbit femurs for four weeks. Both the size and orientation degree of the blood vessels formed in the scaffolds allowing 1D cell migration were 2.5- to 4.0-fold greater than those of the blood vessels formed in the scaffolds allowing 2D and 3D cell migration. Furthermore, the amount of bone formed in the scaffolds allowing 1D cell migration was 1.4-fold larger than that formed in the scaffolds allowing 2D and 3D cell migration. These are probably because the 1D space limited the direction of cell migration and prevented the branching of blood vessels, whereas 2D and 3D spaces provided the opportunity for random cell migration and blood vessel branching. Thus, scaffolds with 1D space are advantageous for inducing large and oriented blood vessels, resulting in a larger amount of bone formation.

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  • Osseointegration enhancement by controlling dispersion state of carbonate apatite in polylactic acid implant Reviewed International journal

    #Cheng Zhang, @Koichiro Hayashi, @Kunio Ishikawa

    Colloids and Surfaces B: Biointerfaces   232   113588 - 113588   2023.12   ISSN:0927-7765 eISSN:1873-4367

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    Osteoconductive ceramics (OCs) are often used to endow polylactic acid (PLA) with osseointegration ability. Conventionally, OC powder is dispersed in PLA. However, considering cell attachment to the implant, OCs may be more favorable when they exist in the form of aggregations, such as granules, and are larger than the cells rather than being dispersed like a powder. In this study, to clarify the effects of the dispersion state of OCs on the osseointegration ability, carbonate apatite (CAp), a bone mineral analog that is osteoconductive and bioresorbable, powder–PLA (P-PLA), and CAp granule–PLA (G-PLA) composite implants were fabricated via thermal pressing. The powder and granule sizes of CAp were approximately 1 and 300–600 µm, respectively. G-PLA exhibited a higher water wettability and released calcium and phosphate ions faster than P-PLA. When cylindrical G-PLA, P-PLA, and PLA were implanted in rabbit tibial bone defects, G-PLA promoted bone maturation compared to P-PLA and pure PLA. Furthermore, G-PLA bonded directly to the host bone, whereas P-PLA bonded across the osteoid layers. Consequently, the bone-to-implant contact of G-PLA was 1.8- and 5.6-fold higher than those of P-PLA and PLA, respectively. Furthermore, the adhesive shear strength of G-PLA was 1.9- and 3.0-fold higher than those of P-PLA and PLA, respectively. Thus, G-PLA achieved earlier and stronger osseointegration than P-PLA or PLA. The findings of this study highlight the significance of the state of dispersion of OCs in implants as a novel strategy for material development.

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  • Gear-shaped carbonate apatite granules with a hexagonal macropore for rapid bone regeneration Invited Reviewed International journal

    @Koichiro Hayashi, @Toshiki Yanagisawa, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    Computational and Structural Biotechnology Journal   21   2514 - 2523   2023.4   ISSN:2001-0370

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    Synthetic bone grafts are in high demand owing to increased age-related bone disorders in the global aging population. Here, we report fabrication of gear-shaped granules (G-GRNs) for rapid bone healing. G-GRNs possessed six protrusions and a hexagonal macropore in the granular center. These were composed of carbonate apatite, i.e., bone mineral, microspheres with ∼1-μm micropores in the spaces between the microspheres. G-GRNs formed new bone and blood vessels (both on the granular surface and within the macropores) 4 weeks after implantation in the rabbit femur defects. The formed bone structure was similar to that of cancellous bone. The bone percentage in the defect recovered to that in a normal rabbit femur at week-4 post-implantation, and the bone percentage remained constant for the following 8 weeks. Throughout the entire period, the bone percentage in the G-GRN-implanted group was ∼10% higher than that of the group implanted with conventional carbonate apatite granules. Furthermore, a portion of the G-GRNs resorbed at week-4, and resorption continued for the following 8 weeks. Thus, G-GRNs are involved in bone remodeling and are gradually replaced with new bone while maintaining a suitable bone level. These findings provide a basis for the design and fabrication of synthetic bone grafts for achieving rapid bone regeneration.

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  • Reconstruction of Load-Bearing Segmental Bone Defects Using Carbonate Apatite Honeycomb Blocks Invited Reviewed International journal

    #Keigo Shibahara, @Koichiro Hayashi, @Yasuharu Nakashima, @Kunio Ishikawa

    ACS Materials Au   3 ( 4 )   321 - 336   2023.4   ISSN:2694-2461 eISSN:2694-2461

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    In a globally aging society, synthetic bone blocks are in increasing demand. An ideal synthetic bone block fuses early with bone and is replaced with new bone at a suitable speed while withstanding the weight load. Herein, we report carbonate apatite honeycomb (HC) blocks with superior mechanical strength, osteoconductivity, and bioresorbability compared to a clinically used synthetic porous block (control block). Three types of HC blocks were fabricated via the debinding of HC green bodies at 600, 650, and 700 °C and subsequent phosphatization, designated as HC-600, HC-650, and HC-700, respectively. The macropores in these HC blocks uniaxially penetrated the blocks, whereas those in the control block were not interconnected. Consequently, the HC blocks exhibited higher open macroporosities (18%-20%) than the control block (2.3%). In contrast, the microporosity of the control block (46.4%) was higher than those of the HC blocks (19%-30%). The compressive strengths of the HC-600, HC-650, HC-700, and control blocks were 24.7, 43.7, 103.8, and 38.9 MPa, respectively. The HC and control blocks were implanted into load-bearing segmental bone defects of rabbit ulnae. Uniaxial HC macropores enabled faster bone ingrowth than the poorly interconnected macropores in the control block. Microporosity in the HC blocks affected bone formation and osteoclastic resorption over a period of 24 weeks. The resorption of HC-650 corresponded to new bone formation; therefore, new bone with strength equal to that of the original bone bridged the separated bones. Thus, the HC blocks achieved the reconstruction of segmental bone defects while withstanding the weight load. The findings of this study contribute to the design and development of synthetic bone blocks for reconstructing segmental defects.

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  • Endowing Osseointegration Ability to Bioinert Alumina by Carbonate Apatite Coating Reviewed International journal

    @Koichiro Hayashi, @Kunio Ishikawa

    Surfaces and Interfaces   36   102617 - 102617   2023.2   ISSN:2468-0230

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    The main reason for revision arthroplasty with an alumina-based prosthesis is aseptic loosening of the prosthesis. To prevent loosening of the prosthesis, endowing bioinert alumina with osteogenic ability is deemed an effective approach. Hence, we developed an alumina substrate with carbonate apatite and evaluated its effectiveness for early binding to the bone. Alumina substrates were coated with carbonate apatite using the following procedures: (1) etching the alumina substrate by alkaline hydrothermal treatment; (2) calcium carbonate coating of the etched alumina substrate; and (3) composition conversion of calcium carbonate coating into carbonate apatite by phosphatization. The tensile bond strength of carbonate apatite coating to alumina substrate was 17.6 MPa, which satisfied the criteria defined by the International Organization for Standardization. Contrary to the results of etched alumina substrates, the carbonate apatite-coated alumina substrates promoted the proliferation and osteogenic differentiation of mesenchymal stem cells and induced mineralization. Furthermore, the carbonate apatite-coated alumina substrates strongly adhered to the rabbit tibia 4 weeks after implantation compared to the etched alumina substrates. The contact area and adhesion strength of carbonate apatite-coated alumina substrates to bone were approximately 19- and 6-fold higher than those of etched alumina substrates, respectively. Thus, carbonate apatite coating may contribute to preventing the loosening of alumina prostheses.

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  • Reconstruction of rabbit mandibular bone defects using carbonate apatite honeycomb blocks with an interconnected porous structure Reviewed International journal

    @Keiko Kudoh, @Naoyuki Fukuda, @Kazuya Akita, @Takaharu Kudoh, @Natsumi Takamaru, @Naito Kurio, @Koichiro Hayashi, @Kunio Ishikawa, @Youji Miyamoto

    Journal of Materials Science: Materials in Medicine   34 ( 1 )   2   2022.12   ISSN:0957-4530 eISSN:1573-4838

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    Abstract

    Carbonate apatite (CO<sub>3</sub>Ap) granules are useful as a bone substitute because they can be remodeled to new natural bone in a manner that conforms to the bone remodeling process. However, reconstructing large bone defects using CO<sub>3</sub>Ap granules is difficult because of their granular shape. Therefore, we fabricated CO<sub>3</sub>Ap honeycomb blocks (HCBs) with continuous unidirectional pores. We aimed to elucidate the tissue response and availability of CO<sub>3</sub>Ap HCBs in the reconstruction of rabbit mandibular bone defects after marginal mandibulectomy. The percentages of the remaining CO<sub>3</sub>Ap area and calcified bone area (newly formed bone) were estimated from the histological images. CO<sub>3</sub>Ap area was 49.1 ± 4.9%, 30.3 ± 3.5%, and 25.5 ± 8.8%, whereas newly formed bone area was 3.0 ± 0.6%, 24.3 ± 3.3%, and 34.7 ± 4.8% at 4, 8, and 12 weeks, respectively, after implantation. Thus, CO<sub>3</sub>Ap HCBs were gradually resorbed and replaced by new bone. The newly formed bone penetrated most of the pores in the CO<sub>3</sub>Ap HCBs at 12 weeks after implantation. By contrast, the granulation tissue scarcely invaded the CO<sub>3</sub>Ap HCBs. Some osteoclasts invaded the wall of CO<sub>3</sub>Ap HCBs, making resorption pits. Furthermore, many osteoblasts were found on the newly formed bone, indicating ongoing bone remodeling. Blood vessels were also formed inside most of the pores in the CO<sub>3</sub>Ap HCBs. These findings suggest that CO<sub>3</sub>Ap HCBs have good osteoconductivity and can be used for the reconstruction of large mandibular bone defects.

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    DOI: 10.1007/s10856-022-06710-2

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    Other Link: https://link.springer.com/article/10.1007/s10856-022-06710-2/fulltext.html

  • Structurally Optimized Honeycomb Scaffolds with Outstanding Ability for Vertical Bone Augmentation Reviewed International journal

    @Koichiro Hayashi, @Masaya Shimabukuro, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    Journal of Advanced Research   41   101 - 112   2022.11   ISSN:2090-1232 eISSN:2090-1224

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    IntroductionCases of intractable dental implant require vertical bone augmentation; however, the predicted bone height and volume are difficult to obtain. In vertical bone augmentation, the contact surface between the scaffold and the bone is limited to the bottom face of the scaffold. Furthermore, the strength decrease caused by scaffold resorption leads to collapse of the augmented site, leading to a decrease in the bone volume and height.ObjectivesTo promote bone ingrowth, we fabricated carbonate apatite (i.e., bone mineral) honeycomb (HC) scaffolds with uniaxial channels vertically penetrating the scaffold. Furthermore, we controlled the scaffold resorption rate, eventually the endurability for compression, and the bone height and volume by controlling the strut thickness.MethodsThe channel aperture was controlled to be 230–260 μm to promote bone ingrowth. Furthermore, the strut thicknesses of the HC scaffolds were adjusted to 100, 200, and 300 μm to control the scaffold resorption; these scaffolds were designated as HC100, HC200, and HC300, respectively.ResultsAt 4 weeks post-implantation on rabbit calvarium, all scaffolds had already vertically augmented new bone close to the top surface of the scaffold. In the following 8 weeks, the height and amount of new bone in all scaffolds increased. Notably, HC300 was resorbed synchronously with new bone formation, allowing it to endure the compression from the fasciae for 12 weeks post-implantation. Furthermore, HC300 formed larger-diameter blood vessels than those of HC100 and HC200.ConclusionThe HC scaffolds surpassed the various combined scaffolds and growth factors or stem cells in the ability for vertical bone augmentation. Thus, the HC structure is inherently suitable for vertical bone augmentation. Notably, the HC scaffolds with 300-μm-thick struts enhanced both new bone formation and angiogenesis. This study revealed a structurally suitable design for achieving an outstanding outcome in vertical bone augmentation.

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  • Channel Aperture Characteristics of Carbonate Apatite Honeycomb Scaffolds Affect Ingrowths of Bone and Fibrous Tissues in Vertical Bone Augmentation Reviewed

    Koichiro Hayashi, Ryo Kishida, Akira Tsuchiya, Kunio Ishikawa

    Bioengineering   9 ( 11 )   627 - 627   2022.11   ISSN:2306-5354 eISSN:2306-5354

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    Synthetic scaffolds with the ability to prevent fibrous tissue penetration and promote bone augmentation may realize guided bone regeneration without the use of a barrier membrane for dental implantation. Here, we fabricated two types of honeycomb scaffolds of carbonate apatite, a bone mineral analog, whose channel apertures were square (HC-S) and rectangular (HC-R). The side lengths of the HC-Ss and HC-Rs were 265.8 ± 8.9; 817.7 ± 2.4 and 267.1 ± 5.2 μm, respectively. We placed cylindrical HC-Ss and HC-Rs on the rabbit calvaria. At 4 weeks post-implantation, the HC-Ss prevented fibrous tissue penetration from the top face via the channels, which allowed the new bone to reach the top of the scaffold from the bottom face or the calvarium. In contrast, in the HC-Rs, fibrous tissues filled the channels in the top region. At 12 weeks post-implantation, the HC-Ss were partially replaced with new bone. In the top region of the HC-Rs, although new bone had formed, fibrous tissue remained. According to the findings here and in our previous study, the longer side length rather than the shorter side length of a rectangular scaffold channel aperture is the dominant factor that affects fibrous tissue penetration and new bone augmentation. Furthermore, even though channel aperture areas are similar, bone and fibrous tissue ingrowths are different when the aperture shapes are different.

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  • Feasibility study on surface morphology regulation of β-tricalcium phosphate bone graft for enhancing cellular response Reviewed International journal

    @Tansza Setiana Putri, @Sunarso, @Koichiro Hayashi, @Kanji Tsuru, @Kunio Ishikawa

    Ceramics International   48 ( 9 )   13395 - 13399   2022.5   ISSN:0272-8842 eISSN:1873-3956

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    Beta-tricalcium phosphate (βTCP) granules are commonly used as an artificial bone graft material. Meanwhile, the surface morphology of the bone graft is an important factor for cellular response. In this study, feasibility study on surface morphology regulation of βTCP bone graft for enhancing cellular response were investigated. The regulation was achieved on the basis of a multistep heating process. Briefly, initial heat treatment of βTCP granules at 1300 °C for 12 h resulted in fabrication of alpha-tricalcium phosphate (αTCP) granules with interconnected micropores. In the second heat treatment, exposure of αTCP granules to 100% relative humidity at 100 °C resulted in partial hydrolysis of αTCP, leading to the fabrication of needle-like calcium-deficient hydroxyapatite (cdHAp) crystals on the αTCP surface. After the third heat treatment at 1100 °C, both cdHAp and αTCP converted back to βTCP, and interconnected micropores with a roughened surface structure were formed. In vitro cell evaluation demonstrated that βTCP granules obtained by the series of heat treatments exhibited 24 times higher cell proliferation at day 9, and four times higher alkaline phosphatase activity compared with untreated βTCP granules. Therefore, we concluded that regulation of surface morphology by a series of heat treatments is useful for improving cellular response to βTCP bone grafting materials.

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  • Granular honeycomb scaffolds composed of carbonate apatite for simultaneous intra- and inter-granular osteogenesis and angiogenesis Reviewed International journal

    @Koichiro Hayashi, @Toshiki Yanagisawa, @Masaya Shimabukuro, @Ryo Kishida, @Kunio Ishikawa

    Materials Today Bio   14   100247 - 100247   2022.3   ISSN:2590-0064

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    Granular porous calcium phosphate scaffolds are used for bone regeneration in dentistry. However, in conventional granules, the macropore interconnectivity is poor and has varying size. Herein, we developed a productive method for fabricating carbonate apatite honeycomb granules with uniformly sized macropores based on extrusion molding. Each honeycomb granule possesses three hexagonal macropores of ∼290 ​μm along its diagonal. Owing to these macropores, honeycomb granules simultaneously formed new and mature bone and blood vessels in both the interior and exterior of the granules at 4 weeks after implantation. The honeycomb granules are useful for achieving rapid osteogenesis and angiogenesis.

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  • Surface functionalization with copper endows carbonate apatite honeycomb scaffold with antibacterial, proangiogenic, and pro-osteogenic activities Reviewed International journal

    @Masaya Shimabukuro, @Koichiro Hayashi, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    Biomaterials Advances   135   212751 - 212751   2022.3   ISSN:2772-9508 eISSN:2772-9508

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    Osteomyelitis is a potentially devastating inflammatory bone disease that leads to bone destruction and loss. Treatment of osteomyelitis requires the removal of residual bacteria as well as osteogenesis with angiogenesis at the site of treatment. Use of an appropriate amount of copper (Cu) in treatment scaffolds may achieve these goals without the risk of toxicity. In this study, the surface of the carbonate apatite honeycomb scaffold was functionalized with Cu through a dissolution–precipitation reaction. The resulting scaffolds retained the honeycomb structure after immersion in CuCl2 solution, and Cu was precipitated on the surface as libethenite [Cu2(OH)PO4]. The surface Cu concentration was controlled by the concentration of the CuCl2 solution. Scaffolds with a surface Cu concentration of 23.8 wt% exhibited antibacterial and cytotoxic effects, whereas those with concentrations of ≤4.6 wt% exerted antibacterial effects without negatively affecting the cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like cells. Furthermore, scaffolds with a surface Cu concentration of 4.6 wt% Cu inhibited bacterial growth for at least 28 days and displayed proangiogenic and pro-osteogenic activities in vivo. These data confirm the success in functionalizing scaffolds with Cu that may be utilized as an innovative osteomyelitis therapy.

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  • Effects of Channels and Micropores in Honeycomb Scaffolds on the Reconstruction of Segmental Bone Defects Reviewed International journal

    #Keigo Shibahara, @Koichiro Hayashi, @Yasuharu Nakashima, @Kunio Ishikawa

    Frontiers in Bioengineering and Biotechnology   10   825831 - 825831   2022.3   ISSN:2296-4185 eISSN:2296-4185

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    The reconstruction of critical-sized segmental bone defects is a key challenge in orthopedics because of its intractability despite technological advancements. To overcome this challenge, scaffolds that promote rapid bone ingrowth and subsequent bone replacement are necessary. In this study, we fabricated three types of carbonate apatite honeycomb (HC) scaffolds with uniaxial channels bridging the stumps of a host bone. These HC scaffolds possessed different channel and micropore volumes. The HC scaffolds were implanted into the defects of rabbit ulnar shafts to evaluate the effects of channels and micropores on bone reconstruction. Four weeks postoperatively, the HC scaffolds with a larger channel volume promoted bone ingrowth compared to that with a larger micropore volume. In contrast, 12 weeks postoperatively, the HC scaffolds with a larger volume of the micropores rather than the channels promoted the scaffold resorption by osteoclasts and bone formation. Thus, the channels affected bone ingrowth in the early stage, and micropores affected scaffold resorption and bone formation in the middle stage. Furthermore, 12 weeks postoperatively, the HC scaffolds with large volumes of both channels and micropores formed a significantly larger amount of new bone than that attained using HC scaffolds with either large volume of channels or micropores, thereby bridging the host bone stumps. The findings of this study provide guidance for designing the pore structure of scaffolds.

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  • Multiscale Porous Scaffolds Constructed of Carbonate Apatite Honeycomb Granules for Bone Regeneration Reviewed International journal

    @Koichiro Hayashi, @Akira Tsuchiya, @Masaya Shimabukuro, @Kunio Ishikawa

    Materials & Design   215   110468 - 110468   2022.3   ISSN:0264-1275 eISSN:1873-4197

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    The use of scaffolds with pores ranging from macroscale to nanoscale (i.e., multiscale pores), is an effective strategy to achieve favorable bone regeneration. Here, we report the fabrication of multiscale porous scaffolds (MPSs) and evaluate the effects of macropores (>100 μm) and micropores (<10 μm) on bone regeneration in the early to medium term. MPSs were constructed from interconnecting carbonate apatite honeycomb granules. The uniaxial macropores penetrating the honeycomb granules linked the gaps among the granules, creating an interconnected macroporous architecture. MPSs with different proportions of macropores and micropores were implanted into rabbit femurs. In an early stage, macropores played a crucial role in promoting new bone formation. In the medium term, micropores, rather than macropores, were the dominant factor affecting the replacement of MPSs with new bone. Notably, micropores of 100 nm to 10 μm primarily promoted MPS resorption by osteoclasts, stimulating secondary osteogenesis. Our findings demonstrated that pore size distribution, rather than porosity, was crucial for osteogenesis in the early-to-medium term. Although conventional scaffold development sacrifices mechanical strength to improve bone formation, our findings indicate that optimizing the pore size distribution is a promising strategy to develop scaffolds that satisfy the requirements of both osteogenesis and mechanical strength.

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  • Fabrication of vaterite blocks from a calcium hydroxide compact Reviewed International journal

    @Kunio Ishikawa, #Pery Freitas, @Ryo Kishida, @Koichiro Hayashi, @Akira Tsuchiya

    Ceramics International   48 ( 3 )   4153 - 4157   2022.2   ISSN:0272-8842 eISSN:1873-3956

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    Metastable vaterite blocks are expected to show high reactivity. However, they have not been reported to date. In this study, the feasibility of fabricating an artificial vaterite block was investigated by exposing a Ca(OH)2 compact to CO2 under several conditions. Under a 100% H2O atmosphere, a calcite block was formed within three days. Under a 100% methanol atmosphere, no carbonation was observed for seven days. Under 90% methanol without atmospheric flow, a vaterite block containing 5 mass% of unreacted Ca(OH)2 and 3 mass% of calcite was formed after 24 h. On day 7, it was transformed into a block with 70 mass% of calcite, 27 mass% of vaterite, and 3 mass% of unreacted Ca(OH)2. By contrast, under 90% methanol with atmospheric flow to remove the accumulated H2O in the compact, a pure CaCO3 block of 98 mass% vaterite and 2 mass% calcite was formed on day 3. Therefore, the regulation of the amount of H2O is important for fabricating vaterite blocks. Porosimetry measurements revealed that the calcite block fabricated under 90% methanol without atmospheric flow demonstrated a pore size profile closer to that of the vaterite block than that of the calcite block fabricated under 100% H2O atmosphere because the vaterite with small spherical crystals was formed initially before its transformation to calcite.

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  • Effects of Pore Interconnectivity on Bone Regeneration in Carbonate Apatite Blocks Reviewed International journal

    #Maab Elsheikh, @Ryo Kishida, @Koichiro Hayashi, @Akira Tsuchiya, @Masaya Shimabukuro, @Kunio Ishikawa

    Regenerative Biomaterials   9 ( 1 )   rbac010   2022.2   ISSN:2056-3418 eISSN:2056-3426

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    <title>Abstract</title>
    Porous architecture in bone substitutes, notably the interconnectivity of pores, is a critical factor for bone ingrowth. However, controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods, such as sintering. Herein, we fabricated a porous block using the crystal growth of calcium sulfate dihydrate, and controlled the pore interconnectivity by limiting the region of crystal growth. The calcium sulfate dihydrate blocks were transformed to bone apatite, carbonate apatite (CO3Ap) through dissolution−precipitation reactions. Thus, CO3Ap blocks with 15% and 30% interconnected pore volumes were obtained while maintaining the microarchitecture: they were designated as CO3Ap-15 and CO3Ap-30, respectively. At 4 weeks after implantation in a rabbit femur defect, new bone formed throughout CO3Ap-30, whereas little bone was formed in the center region of CO3Ap-15. At 12 weeks after implantation, a large portion of CO3Ap-30 was replaced with new bone and the boundary with the host bone became blurred. In contrast, CO3Ap-15 remained in the defect and the boundary with the host bone was still clear. Thus, the interconnected pores promote bone ingrowth, followed by replacement of the material with new bone. These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.

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  • Fabrication and histological evaluation of porous carbonate apatite blocks using disodium hydrogen phosphate crystals as a porogen and phosphatization accelerator Reviewed International journal

    #Pery Freitas, @Ryo Kishida, @Koichiro Hayashi, @Akira Tsuchiya, @Masaya Shimabukuro, @Kunio Ishikawa

    Journal of Biomedical Materials Research Part A   110 ( 6 )   1278 - 1290   2022.2   ISSN:1549-3296 eISSN:1552-4965

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    The porous architecture of artificial bones plays a pivotal role in bone ingrowth. Although salt leaching methods produce predictable porous architectures, their application in the low-temperature fabrication of ceramics remains a challenge. Carbonate apatite (CO3Ap) blocks with three ranges of pore sizes: 100–200, 200–400, and 400–600 μm, were fabricated from CaCO3 blocks with embedded Na2HPO4 crystals as a porogen and accelerator for CaCO3-to-CO3Ap conversion. CaCO3 blocks were obtained from Ca(OH)2 compacts with Na2HPO4 by CO2 flow at 100% humidity. When carbonated under 100% water humidity, the dissolution of Na2HPO4 and the formation of hydroxyapatite were observed. Using 90% methanol and 10% water were beneficial in avoiding the Na2HPO4 consumption and generating the metastable CaCO3 vaterite, which was rapidly converted into CO3Ap in a Na2HPO4 solution in 7 days. For the histological evaluation, the CO3Ap blocks were implanted in rabbit femur defects. Four weeks after implantation, new bone was formed at the edges of the blocks. After 12 weeks, new bone was observed in the central areas of the material. Notably, CO3Ap blocks with pore sizes of 100–200 μm were the most effective, exhibiting approximately 23% new bone area. This study sheds new light on the fabrication of tailored porous blocks and provides a useful guide for designing artificial bones.

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  • No-Observed-Effect Level of Silver Phosphate in Carbonate Apatite Artificial Bone on Initial Bone Regeneration Reviewed

    Masaya Shimabukuro, Koichiro Hayashi, Ryo Kishida, Akira Tsuchiya, Kunio Ishikawa

    ACS Infectious Diseases   8 ( 1 )   159 - 169   2022.1   ISSN:2373-8227 eISSN:2373-8227

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    Fracture-related infections require both treatments for bacteria removal and bone reconstruction. The use of combined broad-spectrum antibacterial silver compounds and artificial bone with high osteogenic activity is considered to be an effective strategy for achieving these treatments in one surgery. However, silver compounds are toxic for living tissues even at low concentrations. Herein, we investigated the no-observed-effect level (NOEL) of silver phosphate (Ag3PO4) in a bone substitute composed of carbonate apatite (CO3Ap), a bone mineral, using in vitro and in vivo experiments. In vitro experiments demonstrated that the CO3Ap artificial bone containing ≥0.1 wt % Ag3PO4 exerted antibacterial effects against Staphylococcus epidermidis, while those containing ≤0.3 wt % Ag3PO4 did not affect cellular adhesion, proliferation, differentiation, and calcification of osteoblast-like MC3T3-E1 cells. In vivo experiments demonstrated that the CO3Ap artificial bone containing ≤0.3 wt % Ag3PO4 replaced a new bone to the same levels as those without Ag3PO4 4 weeks after implantation into the bone defect of the rabbit femur condyle. However, the CO3Ap artificial bone containing 0.3 wt % Ag3PO4 caused an inflammatory reaction, whereas those containing ≤0.1 wt % Ag3PO4 did not. Thus, both bone regeneration and infection control without any adverse effects were achieved using the CO3Ap artificial bone containing 0.1 wt % Ag3PO4, indicating that the NOEL of Ag3PO4 was 0.1 wt %. Our results provide an effective strategy for the treatments of fracture-related infections.

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  • Effects of carbonate ions in phosphate solution on the fabrication of carbonate apatite through a dissolution–precipitation reaction Reviewed International journal

    @Masaya Shimabukuro,@Koichiro Hayashi,@Ryo Kishida,@Akira Tsuchiya,@Kunio Ishikawa

    Ceramics International   48 ( 1 )   1032 - 1037   2022.1   ISSN:0272-8842 eISSN:1873-3956

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    Carbonate apatite (CO3Ap) artificial bone has attracted much attention due to its high osteoconductivity and replacement to bone. CO3Ap is an inorganic component of bone, and has been fabricated by compositional transformation through a dissolution–precipitation reaction in Na2HPO4 solution using calcium carbonate as a precursor. In this study, the effects of the CO32− concentration in the Na2HPO4 solution on the CO3Ap fabrication reaction and the properties of the fabricated CO3Ap were investigated. The rate of the compositional transformation became faster, and more CO3 containing CO3Ap was fabricated using CO32− concentrated in Na2HPO4 solution. The crystal shape of CO3Ap changed from scale-like to hexagonal crystals. In addition, the crystallite size increased with increasing CO32− concentration in the Na2HPO4 solution. These changes lead to larger pores (≥0.02 μm) and decreased number of small pores (<0.02 μm) according to the CO3 content in CO3Ap, even though the total pore volume remained the same. These findings indicate that the CO32− concentration in Na2HPO4 solution is an important factor for the CO3Ap fabrication reaction and affects the properties of the fabricated CO3Ap.

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  • No-Observed-Effect Level of Silver Phosphate in Carbonate Apatite Artificial Bone on Initial Bone Regeneration Reviewed International journal

    @Masaya Shimabukuro, @Koichiro Hayashi, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    ACS Infectious Diseases   8 ( 1 )   159 - 169   2022.1

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    DOI: https://doi.org/10.1021/acsinfecdis.1c00480

  • Honeycomb scaffolds capable of ectopic osteogenesis: Histological evaluation of osteoinduction mechanism Reviewed International journal

    @Koichiro Hayashi, @Kunio Ishikawa

    Nano Select   3 ( 1 )   60 - 77   2022.1   ISSN:2688-4011 eISSN:2688-4011

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    DOI: 10.1002/nano.202000283

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  • 骨・骨髄再生および感染予防用ハニカムスキャフォールド —構造が拓く新機能― Invited Reviewed

    林 幸壱朗

    セラミックス   57 ( 8 )   543 - 545   2022

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  • Honeycomb Scaffolds Capable of Achieving Barrier Membrane-Free Guided Bone Regeneration Reviewed International journal

    @Koichiro Hayashi, @Masaya Shimabukuro, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    Materials Advances   2 ( 23 )   7638 - 7649   2021.12

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    Barrier membrane-free guided bone regeneration (GBR) with a synthetic scaffold may resolve the current challenges in vertical bone augmentation. To realize such GBR, we fabricated carbonate apatite honeycomb (HC) scaffolds capable of preventing soft tissue invasion and enhancing bone ingrowth. These HC scaffolds with 230-, 460-, and 630 μm-aperture channels were designated as HC230, HC460, and HC630, respectively. They were constructed by interconnecting carbonate apatite microspheres; they possessed micropores and nanopores in the struts and were implanted on the rabbit calvarium. The amount of new bone and soft tissues in the HC scaffolds significantly increased and decreased, respectively, with the decrease in the channel aperture size. The new bone height in HC230 at 4 and 12 weeks post-implantation was 3.4 ± 0.5 and 3.8 ± 0.2 mm, respectively, reaching the top edge of the struts. The percent volume of new bone in HC230 at 4 and 12 weeks post-implantation was 38.6% ± 2.2% and 49.9% ± 1.5%, respectively. These findings demonstrated that HC230 augmented faster, higher, and a greater amount of vertical bone growth than the reported combinations of scaffolds and growth factors or barrier membranes. Therefore, the multiscale-architectural control of HC scaffolds may pioneer barrier membrane-free GBR.

    DOI: 10.1039/d1ma00698c

  • Enhancement of bone to polylactic acid plate bonding by carbonate apatite coating Reviewed International journal

    #Cheng Zhang, @Koichiro Hayashi, @Kunio Ishikawa

    Ceramics International   47 ( 20 )   28348 - 28356   2021.10

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    DOI: 10.1016/j.ceramint.2021.06.252

  • Honeycomb Scaffold-Guided Bone Reconstruction of Critical-Sized Defects in Rabbit Ulnar Shafts Reviewed International journal

    #Keigo Shibahara,@Koichiro Hayashi,@Yasuharu Nakashima,@Kunio Ishikawa

    ACS Applied Bio Materials   2021.9

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    DOI: 10.1021/acsabm.1c00533

  • Reconstruction of critical-size segmental defects in rat femurs using carbonate apatite honeycomb scaffolds Reviewed International journal

    #Yuta Sakemi, @Koichiro Hayashi, @Akira Tsuchiya, @Yasuharu Nakashima, @Kunio Ishikawa

    Journal of Biomedical Materials Research Part A   109 ( 9 )   1613 - 1622   2021.9

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    DOI: 10.1002/jbm.a.37157

  • Fabrication of highly interconnected porous carbonate apatite blocks based on the setting reaction of calcium sulfate hemihydrate granules Reviewed International journal

    @Ryo Kishida,#Maab Elsheikh,@Koichiro Hayashi,@Akira Tsuchiya,@Kunio Ishikawa

    Ceramics International   47 ( 14 )   19856 - 19863   2021.7

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    DOI: https://doi.org/10.1016/j.ceramint.2021.03.324

  • Impacts of Channel Direction on Bone Tissue Engineering in 3D-Printed Carbonate Apatite Scaffolds Reviewed International journal

    @Koichiro Hayashi,@Nao Kato,@Masaki Kato,@Kunio Ishikawa

    Materials & Design   204   109686   2021.6

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    Although the channel architecture of a scaffold is critical for bone regeneration, little is known for the channel direction. In this study, four types of carbonate apatite cylindrical scaffolds; scaffolds with biaxial channels (VH-scaffold), with uniaxial vertical channels (V-scaffold), with uniaxial horizontal channels (H-scaffold), and without channels (N-scaffold), were implanted in a rabbit femur defect for 4 and 12 weeks. Although the largest bone was formed 4 weeks post-implantation in the VH-scaffold, newly formed bone disappeared with the scaffold after 12 weeks. Thus, biaxial channels resulted in the rapid dissolution of the scaffold and were counterproductive in long-term bone regeneration. The V-scaffold that had channels connected to the periosteum was gradually resorbed throughout 12 weeks post-implantation. The percentage of mineralized bone in the V-scaffolds was equal to that in the natural bone. The resorption and bone percentage of H-scaffolds that had no channels connected to the periosteum were slower and lower, respectively, than those of V-scaffolds. Thus, channels should be connected to the periosteum to achieve smooth replacement by the new bone. In the N-scaffold, much less bone was formed inside the scaffold. This study contributes to providing a design guide for scaffold development in bone engineering.

    DOI: 10.1016/j.matdes.2021.109686

  • Honeycomb Scaffolds Fabricated Using Extrusion Molding and Sphere Packing Theory for Bone Regeneration Reviewed International journal

    @Koichiro Hayashi, @Kunio Ishikawa

    ACS Applied Bio Materials   4 ( 1 )   721 - 730   2021.1

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    DOI: 10.1021/acsabm.0c01279

  • Protein Corona Components of Polyethylene Glycol-conjugated Organosilica Nanoparticles Modulates Macrophage Uptake Reviewed International journal

    @Hyungjin Kim, @Daniel Röth, @Yasuhiro Isoe, @Koichiro Hayashi, @Chihiro Mochizuki, @Kalkum Markus, @Michihiro Nakamuraa

    Colloids and Surfaces B: Biointerfaces   2020.12

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    DOI: 10.1016/j.colsurfb.2020.111527

  • Effects of Nanopores on the Mechanical Strength, Osteoclastogenesis, and Osteogenesis in Honeycomb Scaffolds(selected as a Journal of Materials Chemistry B HOT Paper) Reviewed International journal

    @Koichiro Hayashi, @Kunio Ishikawa

    Journal of Materials Chemistry B   2020.8

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    The scaffold chemical composition and pore architecture are critical for successful bone regeneration. Although the effects of chemical composition, micron-scale pores, and macropores (Z100 mm) are known, those of nanometer-scale pores (nanopores) are unknown. Here, honeycomb scaffolds (HCSs) composed of carbonate apatite and bone mineral, were fabricated with three distinct nanopore volumes, while other parameters were comparable between HCSs. Their compressive strengths and nanopore volumes linearly correlated. The HCSs were implanted into critical-sized bone defects (CSDs) in the rabbit femur distal epiphyses. The nanopore volume affected both osteoclastogenesis and osteogenesis. HCSs with nanopore volumes of Z0.15 cm3 g-1 promoted osteoclastogenesis, contributing to bone maturation and bone formation within 4 weeks. However, HCSs with nanopore volumes of 0.07 cm3 g-1 promoted significantly less bone maturation and neoformation. Nevertheless, HCSs with nanopore volumes of Z0.18 cm3 g-1 did not undergo continuous bone regeneration throughout the 12 week period due to excessive osteoclastogenesis, which favored HCS resorption over bone neoformation. When the nanopore volume was 0.15 cm3 g-1, osteoclastogenesis and osteogenesis progressed harmonically, resulting in HCS replacement with new bone. Our results demonstrate that the nanopore volume is critical for controlling osteoclastogenesis and osteogenesis. These insights may help establish a coherent strategy for developing scaffolds for different applications.

    DOI: 10.1039/D0TB01498B

  • Tearable and fillable composite sponges capable of heat generation and drug release in response to alternating magnetic field Reviewed International journal

    @Koichiro Hayashi, @Atsuto Tokuda, @Jin Nakamura, @Ayae Sugawara-Narutaki, @Chikara Ohtsuki

    Materials   2020.8

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    DOI: 10.1039/10.3390/ma13163637

  • Near-Infrared Fluorescent Thiol-Organosilica Nanoparticles That Are Functionalized with IR-820 and Their Applications for Long-Term Imaging of in Situ Labeled Cells and Depth-Dependent Tumor in Vivo Imaging Reviewed International journal

    @Michihiro Nakamura, @Koichiro Hayashi, @Junna Nakamura, @Chihiro Mochizuki, @Takuya Murakami, @Hirokazu Miki, @Shuji Ozaki, @Masahiro Abe

    Chemistry of Materials   2020.8

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    Thiol-organosilica nanoparticles that are internally functionalized with IR-820 (thiol-OS/IR820) were prepared via a one-pot process for near-infrared (NIR) fluorescence in vivo imaging. Thiol-OS/IR820 demonstrated broad-band emissive NIR fluorescence with multiple new fluorescent peaks that differed from those of the IR-820 molecule and upconversion fluorescence originated from thiol-OS. Thiol-OS/IR820 was biocompatible and did not show significant toxicity in vitro and in vivo. We conducted in vivo tracking of in situ labeled cells against subcutaneous xenograft cells. The in vivo imaging showed a migration and an accumulation of the in situ labeled cells to the site of xenograft cells. Then, a reduction of the grafted cells was observed after 3 weeks. Next, we conducted in vivo tumor imaging of a mouse with a subcutaneous xenograft tumor using intravenous administration of thiol-OS/IR820. Using three wavelengths of light emission, depth-dependent NIR fluorescence imaging of a mouse with a subcutaneous xenograft tumor was conducted. The accumulation of particles in the tumor tissue due to the enhanced permeability and retention (EPR) effect was observed depth-dependently. NIR fluorescence in vivo imaging using thiol-OS/IR820 is useful for long-term observation and shows substantial promise for the visualization of novel biological phenomena in vivo.

    DOI: 10.1021/acs.chemmater.0c01414

  • Rapid Osseointegration Bestowed by Carbonate Apatite Coating of Rough Titanium Reviewed International journal

    #Rui Shi,@Koichiro Hayashi,@Kunio Ishikawa

    Advanced Materials Interfaces   2020.7

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    Titanium (Ti) implants that realize rapid osseointegration are required for favorable outcomes. Rough implant surfaces favor osseointegration, hence, coating implants with natural bone mineral, i.e., carbonate apatite (CO3Ap), may be effective for osseointegration. To achieve rapid osseointegration, rough-Ti substrates are coated with CO3Ap (CO3Ap-Ti) and the effects are evaluated in vitro and in vivo. For comparison, rough-Ti without coating (rough-Ti) and calcite-coated rough-Ti (calcite-Ti) substrates are fabricated. The adhesive strengths of calcite and CO3Ap to the substrates are ≈56.6 and ≈76.8 MPa, respectively, being significantly higher than the strength defined in ISO13779-2 (15 MPa). Calcite and CO3Ap coatings significantly promote preosteoblastic MC3T3-E1 cell proliferation. Additionally, the CO3Ap coating promotes higher osteogenic differentiation activity than the calcite coating. Implantation of CO3Ap-Ti into rabbit tibia defects prompts bone maturation, compared to calcite-Ti or rough-Ti implantation. The bone-implant contact percentage with CO3Ap-Ti and calcite-Ti is higher than that with rough-Ti. Consequently, CO3Ap-Ti acquires a robust bond with the host bone at an early stage (4 weeks postimplantation), compared to calcite-Ti or rough-Ti: the CO3Ap-Ti–bone bonding strength is ≈1.9- and ≈5.5-fold higher than that of calcite-Ti and rough-Ti, respectively. Thus, CO3Ap coating of Ti implants effectively achieve rapid osseointegration.

    DOI: 10.1002/admi.202000636

  • Effects of macropore size in carbonate apatite honeycomb scaffolds on bone regeneration Reviewed International journal

    @Koichiro Hayashi, @Melvin L. Munar, @Kunio Ishikawa

    Materials Science and Engineering: C   111   110848   2020.6

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    The pore architecture of scaffolds is a critical factor for angiogenesis and bone regeneration. Although the effects of scaffold macropore size have been investigated, most scaffolds feature macropores with poor uniformity and interconnectivity, and other parameters (e.g., microporosity, chemical composition, and strut thickness) differ among scaffolds. To clarify the threshold of effective macropore size, we fabricated honeycomb scaffolds (HCSs) with distinct macropore (i.e., channel) sizes (~100, ~200, and ~300 μm). The HCSs were composed of AB-type carbonate apatite with ~8.5% carbonate ions, i.e., the same composition as human bone mineral. Their honeycomb architecture displayed uniformly sized and orderly arranged channels with extremely high interconnectivity, and all the HCSs displayed ~100-μm-thick struts and 0.06 cm3 g−1 of micropore volume. The compressive strengths of
    HCSs with ~100-, ~200-, and ~300-μm channels were higher than those of reported scaffolds, and decreased with increasing channel size: 62 ± 6, 55 ± 9, and 43 ± 8 MPa, respectively. At four weeks after implantation in rabbit femur bone defects, new bone and blood vessels were formed in all the channels of these HCSs. Notably, the ~300-μm channels were extensively occupied by new bone. We demonstrated that high interconnectivity and uniformity of channels can decrease the threshold of effective macropore size, enabling the scaffolds to maintain high mechanical properties and osteogenic ability and serve as implants for weight-bearing areas.

    DOI: https://doi.org/10.1016/j.msec.2020.110848

  • Fabrication of three-dimensional interconnected porous blocks composed of robust carbonate apatite frameworks Invited Reviewed International journal

    #@Tansza S. Putri, @Koichiro Hayashi, @Kunio Ishikawa

    Ceramics International   2020.5

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    DOI: https://doi.org/10.1016/j.ceramint.2020.05.076

  • Behavioural response of cells and bacteria on single and multiple doped Sr and Ag S53P4 Sol-Gel Bioglass Reviewed International journal

    #@Thet Thet Swe, @Khairul Anuar Shariff, @Hasmaliza Mohamad, @Kunio Ishikawa, @Koichiro Hayashi, @Mohamad Hafizi Abu Bakar

    Ceramics International   2020.4

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    DOI: https://doi.org/10.1016/j.ceramint.2020.04.094

  • Granular Honeycombs Composed of Carbonate Apatite, Hydroxyapatite, and β-Tricalcium Phosphate as Bone Graft Substitutes: Effects of Composition on Bone Formation and Maturation Reviewed International journal

    @Koichiro Hayashi, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    ACS Applied Bio Materials   3 ( 3 )   1787 - 1795   2020.3

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    DOI: https://doi.org/10.1021/acsabm.0c00060

  • Effects of surface roughening and calcite coating of titanium on cell growth and differentiation Reviewed International journal

    #Rui Shi, @Koichiro Hayashi, @LT Bang, @Kunio Ishikawa

    Journal of Biomaterials Applications   34   917 - 927   2020.2

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  • Bone regeneration using β-tricalcium phosphate (β-TCP) block with interconnected pores made by setting reaction of β-TCP granules Reviewed International journal

    #Tansza Setiana Putri, @Koichiro Hayashi, @Kunio Ishikawa

    Journal of Biomedical Materials Research Part A   ( 108 )   625 - 632   2020.1

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  • Fabrication and Histological Evaluation of Porous Carbonate Apatite Block from Gypsum Block Containing Spherical Phenol Resin as a Porogen Reviewed International journal

    #Yuta Sakemi, @Koichiro Hayashi,@ Akira Tsuchiya, @Yasuharu Nakashima, @Kunio Ishikawa

    Materials   12   3997   2019.12

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    DOI: https://doi.org/10.3390/ma12233997

  • Carbonate Apatite Micro-Honeycombed Blocks Generate Bone Marrow-Like Tissues as well as Bone Reviewed International journal

    @Koichiro Hayashi, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    Advanced Biosystems   2019.9

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  • Honeycomb blocks composed of carbonate apatite, β-tricalcium phosphate, and hydroxyapatite for bone regeneration: effects of composition on biological responses Reviewed International journal

    @Koichiro Hayashi, @Ryo Kishida, @Akira Tsuchiya, @Kunio Ishikawa

    Materials Today Bio   4   100031   2019.9

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    Synthetic scaffolds exhibiting bone repair ability equal to that of autogenous bone are required in the fields of orthopedics and dentistry. A suitable synthetic bone graft substitute should induce osteogenic differentiation of mesenchymal stem cells, osteogenesis, and angiogenesis. In this study, three types of honeycomb blocks (HCBs), composed of hydroxyapatite (HAp), β-tricalcium phosphate (TCP), and carbonate apatite (CO3Ap), were fabricated, and the effects of HCB composition on bone formation and maturation were investigated. The HC structure was selected to promote cell penetration and tissue ingrowth. HAp and β-TCP HCBs were fabricated by extrusion molding followed by sintering. The CO3Ap HCBs were fabricated by extrusion molding followed by sintering and dissolution-precipitation reactions. These HCBs had similar macroporous structures: all harbored uniformly distributed macropores (∼160 ​μm) that were regularly arrayed and penetrated the blocks unidirectionally. Moreover, the volumes of macropores were nearly equal (∼0.15 ​cm3/g). The compressive strengths of CO3Ap, HAp, and β-TCP HCBs were 22.8 ​± ​3.5, 34.2 ​± ​3.3, and 24.4 ​± ​2.4 ​MPa, respectively. Owing to the honeycomb-type macroporous structure, the compressive strengths of these HCBs were higher than those of commercial scaffolds with intricate three-dimensional or unidirectional macroporous structure. Notably, bone maturation was markedly faster in CO3Ap HCB grafting than in β-TCP and HAp HCB grafting, and the mature bone area percentages for CO3Ap HCBs at postsurgery weeks 4 and 12 were 14.3- and 4.3-fold higher and 7.5- and 1.4-fold higher than those for HAp and β-TCP HCBs, respectively. The differences in bone maturation and formation were probably caused by the disparity in concentrations of calcium ions surrounding the HCBs, which were dictated by the inherent material resorption behavior and mechanism; generally, CO3Ap is resorbed only by osteoclastic resorption, HAp is not resorbed, and β-TCP is rapidly dissolved even in the absence of osteoclasts. Besides the composition, the microporous structure of HC struts, inevitably generated during the formation of HCBs of various compositions, may contribute to the differences in bone maturation and formation.

  • Carbonate apatite granules with uniformly sized pores that arrange regularly and penetrate straight through granules in one direction for bone regeneration Reviewed International journal

    @Koichiro Hayashi, @Melvin L. Munar, @Kunio Ishikawa

    Ceramics International   45   15429 - 15434   2019.5

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  • Fabrication and Evaluation of Interconnected Porous Carbonate Apatite from Alpha Tricalcium Phosphate Spheres Reviewed International journal

    @Kunio Ishikawa, #Tya Arifta, @Koichiro Hayashi, Kanji Tsuru

    Journal of Biomedical Materials Research: Part B - Applied Biomaterials   107 ( 2 )   269 - 277   2019.2

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  • Synthesis of titania nanoparticle-dispersed hybrid membranes fromallyloxytitanium and phosphonic acid derivatives for fuel cell Reviewed International journal

    Naoya Ozawa, @Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Journal of Membrane Science   563   221 - 228   2018.10

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  • Physical and Histological Comparison of Hydroxyapatite, Carbonate Apatite, and β-Tricalcium Phosphate Bone Substitutes Reviewed International journal

    @Kunio Ishikawa, Youji Miyamoto, @Akira Tsuchiya, @Koichiro Hayashi, Kanji Tsuru and Go Ohe

    Materials   11   1993   2018.10

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  • Hydroxyl Radical-Suppressing Mechanism and Efficiency of Melanin-Mimetic Nanoparticles (invited) Invited Reviewed International journal

    @Koichiro Hayashi, Atsuto Tokuda, and Wataru Sakamoto

    International Journal of Molecular Sciences   2018.8

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  • Red Blood Cell-Shaped Microparticles with Red Blood Cell Membrane Demonstrate Prolonged Circulation Time in Blood Reviewed International journal

    @Koichiro Hayashi, Shota Yamada, Wataru Sakamoto, Eri Usugi, Masatoshi Watanabe, and Toshinobu Yogo

    ACS Biomaterials Science & Engineering   2018.7

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  • Cellulose-Based Molecularly Imprinted Red-Blood-Cell-Like Microparticles for the Selective Capture of Cortisol Reviewed International journal

    @Koichiro Hayashi, Hikaru Hayashi, Shota Yamada, Wataru Sakamoto, Toshinobu Yogo

    Carbohydrate Polymers   193   173 - 178   2018.4

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    Magnetite-nanoparticle-containing red-blood-cell-like-microparticles (M-RBC-MPs) with a selective ability for trapping cortisol (COR) were synthesized by an electrospray technique of a molecularly imprinted ethyl(hydroxyethyl) cellulose (EHEC)-based precursor. The as-synthezied M-RBC-MPs were ∼3-μm-disks with a dent. MRBC-MPs contained magnetite nanoparticles below 15 nm in diameter, which exhibited magnetization and no room-temperature coercivity. The molecularly imprinted M-RBC-MPs (MI-M-RBC-MPs) passed through pores less than their diameter. The MI-M-RBC-MPs selectively trapped COR from a solution containing molecules similar to COR, whereas non-imprinted M-RBC-MPs did not trap COR. Furthermore, magnets were used to capture the water-dispersed MI-M-RBC-MPs flowing in a tube. Based on the above results, MI-M-RBC-MPs may selectively trap COR while simultaneously circulating in the blood, followed by their removal from the blood using magnets.

  • Organic-inorganic Hybrid Hollow Nanoparticles Suppress Oxidative Stress and Repair Damaged Tissues for Treatment of Hepatic Fibrosis Reviewed International journal

    @Koichiro Hayashi, Takuma Maruhashi, Wataru Sakamoto, Toshinobu Yogo

    Advanced Functional Materials   28   2018.3

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    Current therapeutic options for the treatment of liver fibrosis are limited, and transplantation is often the only effective option for end-stage fibrotic diseases. To overcome this problem, a nanoparticle-based treatment as an alternative to transplantation is developed. Multifunctional organic–inorganic hybrid hollow nanoparticles (HNPs) containing silibinin are synthesized by mixing precursors in ammonia water at 60 °C for 1 min. The HNPs are mainly composed of siloxanes and disulfides and have surface thiols. The disulfides are cleaved by intracellular glutathione and reduced to thiols, leading to the deformation of the HNPs. Silibinin molecules are released through the cracks formed by HNP deformation. Furthermore, the HNPs suppress the generation of hydroxyl radicals, a major cause of liver fibrosis, via sulfenylation reactions of HNP thiols. Retinol-modified HNPs target Kupffer cells and hepatic stellate cells, which are essential for hepatic fibrogenesis. The combined suppression of hydroxyl radical generation and release of silibinin using the HNPs decreases the proportion of fibrotic tissues and improves hepatic function. The therapeutic efficacy is greater than can be achieved by the suppression of hydroxyl radical generation alone and the injection of silibinin alone. Thus, HNPs are promising for the treatment of liver fibrosis.

  • Red Blood Cell-like Particles with the Ability to Avoid Lung and Spleen Accumulation for the Treatment of Liver Fibrosis Reviewed International journal

    @Koichiro Hayashi, Shota Yamada, Hikaru Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Biomaterials   156   2018.2

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  • Fabrication of Lead-Free Piezoelectric Li2CO3-Added (Ba,Ca)(Ti,Sn)O3 Ceramics under Controlled Low Oxygen Partial Pressure and Their Properties Reviewed International journal

    Kouta Noritake, Wataru Sakamoto, Isamu Yuitoo, Teruaki Takeuchi, @Koichiro Hayashi, Toshinobu Yogo

    Japanese Journal of Applied Physics   57   2018.2

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  • Effective impairment of myeloma cells and their progenitors by hyperthermia Reviewed International journal

    Hirokazu Miki, Shingen Nakamura, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Ariunzaya Bat-Erdene, Yusaku Maeda, Masahiro Oura, Mamiko Takahashi, Masami Iwasa, Takeshi Harada, Shiro Fujii, Kiyoe Kurahashi, Sumiko Yoshida, Kumiko Kagawa, Itsuro Endo, Kenichi Aihara, Mariko Ikuo, Kohji Itoh, @Koichiro Hayashi, Michihiro Nakamura and Masahiro Abe

    Oncotarget   9   2018.2

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  • Metallic Glass Separators for Fuel Cells at Intermediate Temperatures Reviewed International journal

    Masaya Takemoto, Masatomo Hattori, @Koichiro Hayashi, Shin-ichi Yamaura, Wei Zhang, Wataru Sakamoto, Toshinobu Yogo

    Materials Letters   206   2017.11

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  • Fabrication and Properties of Nonreducible Lead-Free Piezoelectric Mn-Doped (Ba,Ca)TiO3 Ceramics Reviewed International journal

    Wataru Sakamoto, Kouta Noritake, Hiroki Ichikawa, @Koichiro Hayashi, Toshinobu Yogo

    Ceramics International   43   2017.8

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  • Synthesis of Inorganic-organic Hybrid Membranes Consisting of Organotrisiloxane Linkages and Their Fuel Cell Properties at Intermediate Temperatures Reviewed International journal

    Masaya Takemoto, @Koichiro Hayashi, Shin-ichi Yamaura, Wei Zhang, Wataru Sakamoto, Toshinobu Yogo

    Polymer   120   2017.6

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  • Organic-Inorganic Hybrid Nanoparticles for Tracking the Same Cells Seamlessly at the Cellular, Tissue, and Whole Body Levels Reviewed International journal

    @Koichiro Hayashi, Yusuke Sato, Hiroki Maruoka, Wataru Sakamoto, and Toshinobu Yogo

    ACS Biomaterials Science & Engineering   3   2017.6

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  • Mesoscopic Multimodal Imaging Provides New Insight to Tumor Tissue Evaluation: An Example of Macrophage Imaging of Hepatic Tumor using Organosilica Nanoparticles Reviewed International journal

    Michihiro Nakamura, @Koichiro Hayashi, Hitoshi Kubo, Masafumi Harada, Keisuke Izumi, Yoshihiro Tsuruo, and Toshinobu Yogo

    Scientific Reports   7   2017.6

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  • Relaxometric Property of Organosilica Nanoparticles Internally Functionalized with Iron Oxide and Fluorescent Dye for Multimodal Imaging Reviewed International journal

    Michihiro Nakamura, @Koichiro Hayashi, Hitoshi Kubo, Takafumi Kanadani, Masafumi Harada, Toshinobu Yogo

    Journal of Colloid and Interface Science   49   2017.4

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  • Theranostic Nanoparticles for MRI-Guided Thermochemotherapy: Tight Clustering of Magnetic Nanoparticles Boosts Relaxivity and Heat-Generation Power Reviewed International journal

    @Koichiro Hayashi, Yoshitaka Sato, Wataru Sakamoto, Toshinobu Yogo

    ACS Biomaterials Science & Engineering   3   2017.1

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  • One-Pot Synthesis of Dual Stimulus-Responsive Degradable Hollow Hybrid Nanoparticles for Image-guided Trimodal Therapy Reviewed International journal

    @Koichiro Hayashi, Takuma Maruhashi, Michihiro Nakamura, Wataru Sakamoto, Toshinobu Yogo

    Advanced Functional Materials   26   2016.12

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  • Synthesis of Inorganic-Organic Hybrid Membranes Consisting of Triazole Linkages Formed by the Azide-Alkyne Click Reaction Reviewed International journal

    Naoya Ozawa, @Koichiro Hayashi, Shin-ichi Yamaura, Wei Zhang, Wataru Sakamoto, Toshinobu Yogo

    Journal of Membrane Science   517   2016.11

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  • Photocurrent Enhancement of Chemically Synthesized Ag Nanoparticle-Embedded BiFeO3 Thin Films Reviewed International journal

    Rika Maruyama, Wataru Sakamoto, Isamu Yuitoo, Teruaki Takeuchi, @Koichiro Hayashi, Toshinobu Yogo

    Japanese Journal of Applied Physics   55   2016.10

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  • One-Pot Synthesis of Inorganic/Organic Hybrid Membranes from Organoalkoxysilane, Hydroimidazole Derivative, and Cyclic Sulfonic Acid Ester Reviewed International journal

    Koji Takahashi, Junji Umeda, @Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Journal of Materials Science   51   2016.4

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  • Smart Ferrofluid with Quick Gel Transformation in Tumors for MRI-Guided Local Magnetic Thermochemotherapy Reviewed International journal

    @Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Advanced Functional Materials   26   2016.3

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  • One-Pot Synthesis of Proton-Conductive Inorganic–Organic Hybrid Membranes from Organoalkoxysilane and Phosphonic Acid Derivatives Reviewed International journal

    Tatsuo Hoshino, @Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Journal of Membrane Science   502   2016.3

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  • Effect of Texturing on Polarization Switching Dynamics in Ferroelectric Ceramics Reviewed International journal

    Sergey Zhukov, Yuri A. Genenko, Jurij Koruza, Jan Schultheiß, Heinz von Seggern, Wataru Sakamoto, Hiroki Ichikawa, Tatsuro Murata, @Koichiro Hayashi, Toshinobu Yogo

    Applied Physics Letters   108   2016.1

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  • Enhancement of Photoinduced Electrical Properties of Al-Doped ZnO/BiFeO3 Layered Thin Films Prepared by Chemical Solution Deposition Reviewed International journal

    Takeshi Katayama, Wataru Sakamoto, Isamu Yuitoo, Teruaki Takeuchi, @Koichiro Hayashi, Toshinobu Yogo

    Japanese Journal of Applied Physics   54   2015.9

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  • Identification of Polyethylene Glycol-Resistant Macrophages on Stealth Imaging in Vitro Using Fluorescent Organosilica Nanoparticles Reviewed International journal

    Michihiro Nakamura, @Koichiro Hayashi, Mutsuki Nakano, Takafumi Kanadani, Kazue Miyamoto, Toshinari Kori, Kazuki Horikawa

    ACS Nano   9   2015.2

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  • Iodinated Silica/Porphyrin Hybrid Nanoparticles for X-Ray Computedtomography/Fluorescence Dual-Modal Imaging of Tumors Reviewed International journal

    @Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Journal of Asian Ceramic Societies   2   2014.12

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  • Development and Potential Theranostic Applications of a Self-Assembled Hybrid of Magnetic Nanoparticle Clusters with Polysaccharide Nanogels Reviewed International journal

    Kiyofumi Katagiri, Keiko Ohta, Kaori Sako, Kei Inumaru, @Koichiro Hayashi, Yoshihiro Sasaki, Kazunari Akiyoshi

    ChemPlusChem   79   2014.11

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  • Magnetically Responsive Smart Nanoparticles for Cancer Treatment with a Combination of Magnetic Hyperthermia and Remote-Control Drug Release Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Hirokazu Miki, Shuji Ozaki, Masahiro Abe, Toshio Matsumoto, Wataru Sakamoto, Toshinobu Yogo, Kazunori Ishimura

    Theranostics   4   2014.6

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  • Photostable Iodinated Silica/Porphyrin Hybrid Nanoparticles with Heavy-Atom Effect for Wide-Field Photodynamic/Photothermal Therapy Using Single Light Source Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Hirokazu Miki, Shuji Ozaki, Masahiro Abe, Toshio Matsumoto, Kazunori Ishimura

    Advanced Functional Materials   24   2014.1

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  • One-Pot Synthesis of Magnetic Nanoparticles Assembled on Polysiloxane Rod and Their Response to Magnetic Field Reviewed International journal

    @Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Colloid and Polymer Science   291   2013.12

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  • Superparamagnetic Nanoparticle Clusters for Cancer Theranostics Combining Magnetic Resonance Imaging and Hyperthermia Treatment Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Wataru Sakamoto, Toshinobu Yogo, Hirokazu Miki, Shuji Ozaki, Masahiro Abe, Toshio Matsumoto, Kazunori Ishimura

    Theranostics   3   2013.4

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  • Gold Nanoparticle Cluster/Plasmon-Enhanced Fluorescent Silica Core-Shell Nanoparticles for X-Ray Computed Tomography/Fluorescence Dual-Mode Imaging of Tumors Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Hirokazu Miki, Shuji Ozaki, Masahiro Abe, Toshio Matsumoto, Kazunori Ishimura

    Chemical Communications   49   2013.4

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  • Near-Infrared Fluorescent Silica-Coated Gold Nanoparticle Clusters for X-Ray Computed Tomography/Optical Dual Modal Imaging of the Lymphatic System Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Kazunori Ishimura

    Advanced Healthcare Materials   2   2013.3

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  • Time-Lapse Fluorescence Imaging and Quantitative Single Cell and Endosomal Analysis of Peritoneal Macrophages Using Fluorescent Organosilica Nanoparticles Reviewed International journal

    Michihiro Nakamura, Kazunori Miyamoto, @Koichiro Hayashi, Aziz Awaad, Masahito Ochiai, Kazunori Ishimura

    Nanomedicine: Nanotechnology, Biology, and Medicine   9   2013.2

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  • Synthesis and 3D Hierarchical Organization of 2D Structured Iron Oxide Based on Enzymatic Structure, Activity and Thermostability Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Wataru Sakamoto, Toshinobu Yogo, Kazunori Ishimura

    Materials Research Bulletin   47   2012.12

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  • Thiol-Organosilica Particles Internally Functionalized with Propidium Iodide as a Multicolor Fluorescence and X-ray Computed Tomography Probe and Application for Non-Invasive Functional Gastrointestinal Tract Imaging Reviewed International journal

    Michihiro Nakamura, Aziz Awaad, @Koichiro Hayashi, Kazuhiko Ochiai, Kazunori Ishimura

    Chemistry of Materials   24   2012.10

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  • Near-Infrared Fluorescent Silica/Porphyrin Hybrid Nanorings for In Vivo Cancer Imaging Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Hirokazu Miki, Shuji Ozaki, Masahiro Abe, Toshio Matsumoto, Kazunori Ishimura

    Advanced Functional Materials   22   2012.9

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  • In Situ Synthesis of Cobalt Ferrite Nanoparticle/Polymer Hybrid from a Mixed Fe-Co Methacrylate for Magnetic Hyperthermia Reviewed International journal

    @Koichiro Hayashi, Kazuki Maeda, Makoto Moriya, Wataru Sakamoto, Toshinobu Yogo

    Journal of Magnetism and Magnetic Materials   324   2012.9

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  • Silica-Porphyrin Hybrid Nanotubes for In Vivo Cell Tracking by Near-Infrared Fluorescence Imaging Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Kazunori Ishimura

    Chemical Communications   48   2012.2

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  • Synthesis and Photocatalytic Activity of Sea Urchin-Shaped Rutile TiO2 Nanocrystals Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Yoji Makita, Rise Fujiwara, Toshinari Kori, Kazunori Ishimura

    Materials Letters   65   2011.10

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  • Formation of TiO2 Nanostructures by Enzyme-Mediated Self-Assembly for the Destruction of Macrophages Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Wataru Sakamoto, Toshinobu Yogo, Toshinari Kori, Kazunori Ishimura

    Chemistry of Materials   23   2011.7

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  • In Situ Synthesis and Photoresponsive Rupture of Organosilica Nanocapsules Reviewed International journal

    @Koichiro Hayashi, Michihiro Nakamura, Kazunori Ishimura

    Chemical Communications   47   2010.11

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  • Electrosprayed Synthesis of Red-Blood-Cell-Like Particles with Dual-Modality for Magnetic Resonance and Fluorescence Imaging Reviewed International journal

    @Koichiro Hayashi, Kenji Ono, Hiromi Suzuki, Makoto Sawada, Makoto Moriya, Wataru Sakamoto, Toshinobu Yogo

    Small   6   2010.11

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  • High-Frequency, Magnetic Field-Responsive Drug Release from Magnetic Nanoparticle/Organic Hybrid Based on Hyperthermic Effect Reviewed International journal

    @Koichiro Hayashi, Kenji Ono, Hiromi Suzuki, Makoto Sawada, Makoto Moriya, Wataru Sakamoto, Toshinobu Yogo

    ACS Applied Materials & Interfaces   2   2010.7

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  • One-Pot Biofunctionalization of Magnetic Nanoparticles via Thiol-Ene Click Reaction for Magnetic Hyperthermia and Magnetic Resonance Imaging Reviewed International journal

    @Koichiro Hayashi, Kenji Ono, Hiromi Suzuki, Makoto Sawada, Makoto Moriya, Wataru Sakamoto, Toshinobu Yogo

    Chemistry of Materials   22   2010.6

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  • Chemoselective Synthesis of Folic Acid-Functionalized Magnetite Nanoparticles via Click Chemistry for Magnetic Hyperthermia Reviewed International journal

    @Koichiro Hayashi, Makoto Moriya, Wataru Sakamoto, Toshinobu Yogo

    Chemistry of Materials   21   2009.4

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  • Magnetic and Rheological Properties of Monodisperse Fe3O4 Nanoparticle/Organic Hybrid Reviewed International journal

    @Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Journal of Magnetism and Magnetic Materials   321   2009.3

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  • Synthesis of Spinel Iron Oxide Nanoparticle/Organic Hybrid for Hyperthermia Reviewed International journal

    @Koichiro Hayashi, Toshifumi Shimizu, Hidefumi Asano, Wataru Sakamoto, Toshinobu Yogo

    Journal of Materials Research   23   2008.12

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  • Synthesis of Highly Transparent Lithium Ferrite Nanoparticle/Polymer Hybrid Self-standing Films Exhibiting Faraday Rotation in the Visible Region Reviewed International journal

    @Koichiro Hayashi, Rintaro Fujikawa, Wataru Sakamoto, Mitsuteru Inoue, Toshinobu Yogo

    Journal of Physical Chemistry C   112   2008.9

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  • In Situ Synthesis of Lithium Ferrite Nanoparticle/Polymer Hybrid Reviewed International journal

    @Koichiro Hayashi, Wataru Sakamoto, Toshinobu Yogo

    Journal of Materials Research   22   2007.4

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▼display all

Books

  • セラミックデータブック2017/2018

    林幸壱朗

    工業製品技術協会  2017.12 

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Presentations

  • 軟骨再生能を有する 木材由来ハイドロゲルの合成 Invited

    林 幸壱朗

    日本バイオマテリアル学会シンポジウム2024  2024.10 

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    Event date: 2024.10

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  • 抗菌性ハニカム人工骨の開発 Invited

    @林 幸壱朗

    第42回整形外科バイオマテリアル研究会  2023.12 

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    Event date: 2024.4

    Language:Japanese  

    Country:Japan  

  • 炭酸アパタイト人工骨の構造・形状制御による骨再生増強と新機能発現 Invited

    @林 幸壱朗

    第41回日本骨代謝学会学術集会  2023.7 

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    Event date: 2024.4

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Country:Japan  

  • 人工造血幹細胞ニッチとして働く炭酸アパタイトハニカム材料の開発と造血への応用 Invited

    林 幸壱朗

    MIMS 研究集会 「広い意味での防災にまつわる実験数理融合アプローチの新展開」  2023.10 

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    Event date: 2023.10

    Language:Japanese  

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  • 形状可変性炭酸アパタイトチェーンの創製と骨再生への応用

    林幸壱朗, 岸田良, 土谷享, 石川邦夫

    日本セラミックス協会 第36回秋季シンポジウム  2023.9 

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    Event date: 2023.9

    Language:Japanese  

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  • 炭酸アパタイト人工骨の構造・形状制御による骨再生増強と新機能発現 Invited

    林 幸壱朗

    第41回日本骨代謝学会学術集会  2023.7 

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    Event date: 2023.7

    Language:Japanese  

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  • 炭酸アパタイトハニカム材料の人工造血幹細胞ニッチへの応用

    林幸壱朗, 岸田良, 土谷享, 石川邦夫

    公益社団法人日本セラミックス協会 2023年年会  2023.3 

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    Event date: 2023.3

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  • 炭酸アパタイトハニカムスキャフォールドの人工造血幹細胞ニッチとしての応用可能性(ハイライト講演)

    林幸壱朗, 岸田良, 土谷享, 石川邦夫

    第44回日本バイオマテリアル学会大会  2022.11 

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    Event date: 2022.11

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  • Carbonate Apatite Honeycomb Scaffolds for Bone Regeneration Invited

    Koichiro Hayashi

    Functional Inorganic Material  2022.10 

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    Event date: 2022.10

    Language:English   Presentation type:Oral presentation (invited, special)  

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  • ハニカムスキャフォールド:抗菌性、骨誘導、整形外科・歯科応用 Invited

    @林 幸壱朗

    第43回日本バイオマテリアル学会  2021.10 

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    Event date: 2021.10

    Language:Japanese  

    Country:Japan  

  • Honeycomb scaffolds: vertical bone augmentation and antibacterial effects Invited

    @Koichiro Hayashi

    Japanese Association for Dental Research  2021.10 

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    Event date: 2021.10

    Language:English  

    Country:Japan  

  • ハニカムスキャフォールドの微構造が垂直的骨造成に与える影響(トピックス講演)

    @林幸壱朗, @石川邦夫

    セラミックス協会第34回秋期シンポジウム  2021.9 

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    Event date: 2021.9

    Language:Japanese  

    Country:Japan  

  • Impacts of Pore Architecture on Bone Regeneration in Honeycomb Scaffolds Invited International conference

    @Koichiro Hayashi

    KOB & OBT Research Center Joint International Symposium 2021  2021.2 

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    Event date: 2021.2

    Language:English   Presentation type:Oral presentation (invited, special)  

    Venue:Fukuoka   Country:Japan  

  • 機能性微粒子の作成と医療応用 Invited

    @林 幸壱朗

    2019.3 

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    Event date: 2020.7

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Venue:津   Country:Japan  

  • 炭酸アパタイトハニカムスキャホールドの骨誘導能評価

    @林 幸壱朗,@石川 邦夫

    第75回日本歯科理工学会学術講演会  2020.4 

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    Event date: 2020.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:塩尻   Country:Japan  

  • 炭酸アパタイトハニカム構造体の作製と骨および骨髄再生

    @林幸壱朗、@石川邦夫

    2019年3月 日本セラミックス協会年会  2019.3 

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    Event date: 2019.6

    Language:Japanese  

    Country:Japan  

  • ウサギ大腿骨へ埋植した炭酸アパタイト顆粒の吸収性に関する評価

    @土谷享、@林幸壱朗、杉浦悠紀、@石川邦夫

    第39回日本バイオマテリアル学会大会  2017.11 

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    Event date: 2019.6

    Language:Japanese  

    Country:Japan  

  • 炭酸アパタイト顆粒のイヌ抜歯窩における吸収性評価

    杉浦悠紀、@林幸壱朗、@土谷享、@石川邦夫

    第39回日本バイオマテリアル学会大会  2017.11 

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    Event date: 2019.6

    Language:Japanese  

    Venue:東京   Country:Japan  

  • 炭酸アパタイト顆粒のin vitroにおける溶解性試験

    @林幸壱朗、@土谷享、杉浦悠紀、@石川邦夫

    第39回日本バイオマテリアル学会大会  2017.11 

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    Event date: 2019.6

    Language:Japanese  

    Venue:東京   Country:Japan  

  • ウサギ大腿骨へ埋植した炭酸アパタイト顆粒における骨置換率の評価

    @林幸壱朗、@土谷享、杉浦悠紀、@石川邦夫

    第39回日本バイオマテリアル学会大会  2017.11 

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    Event date: 2019.6

    Language:Japanese  

    Venue:東京   Country:Japan  

  • 有機-無機ハイブリッド中空ナノ粒子の合成と肝硬変治療への応用

    @林 幸壱朗、丸橋 卓磨、坂本 渉、余語 利信

    日本セラミックス協会東海支部 2018年度学術研究発表会  2018.12 

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    Event date: 2019.6

    Language:Japanese  

    Country:Japan  

  • 多機能性微粒子の合成と医療応用 Invited

    @林 幸壱朗

    第8回日本バイオマテリアル学会九州ブロック講演会  2018.12 

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    Event date: 2019.6

    Language:Japanese  

    Country:Japan  

  • Multifunctional Organic-Inorganic Hybrid Hollow Nanoparticles for Treatment of Hepatic Fibrosis International conference

    @Koichiro Hayashi, Takuma Maruhashi, Wataru Sakamoto, Toshinobu Yogo

    6th International Conference on Multifunctional, Hybrid and Nanomaterials  2019.3 

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    Event date: 2019.6

    Language:English  

    Country:Spain  

  • 気孔径が炭酸アパタイトハニカムの骨伝導性に及ぼす影響

    @石川邦夫、@林幸壱朗、@土谷享、都留寛治、杉浦悠紀

    第40回日本バイオマテリアル学会大会  2018.11 

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    Event date: 2018.11

    Language:Japanese  

    Venue:神戸国際会議場   Country:Japan  

  • Fabrication of porous beta-TCP block by jeating beta-TCP granules bridged with DCPD

    #Tansza Putri, @Melvin L. Munar, @Koichiro Hayashi, Kanji Tsuru, @Kunio Ishikawa

    Bioceramics 30  2018.10 

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    Event date: 2018.10

    Language:Japanese  

    Venue:Nagoya   Country:Japan  

  • Fabrication of carbonate apatite honeycomb and its tissue response International conference

    @Kunio Ishikawa, @Melvin Munar, @Koichiro Hayashi

    29th Annual Congress of the European Society for Biomaterials  2018.9 

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    Event date: 2018.9

    Language:Japanese  

    Venue:Maastricht   Country:Netherlands  

  • Fabrication of carbonate apatite honeycomb granules International conference

    @K. Ishikawa, @M. Munur, @K. Hayashi

    96th General Session & Exhibition of the International Association for Dental Research  2018.7 

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    Event date: 2018.7

    Language:Japanese  

    Venue:London   Country:United Kingdom  

  • ウサギ大腿骨へ埋植した炭酸アパタイト顆粒における骨置換率の評価

    @石川邦夫、@林幸壱朗、@土谷享、杉浦悠紀

    第39回日本バイオマテリアル学会大会  2017.11 

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    Event date: 2017.11

    Language:Japanese  

    Venue:東京   Country:Japan  

  • ハイブリッド中空ナノ粒子を用いた肝線維化治療

    @林幸壱朗, 丸橋卓磨, 坂本渉, 余語利信

    第39回日本バイオマテリアル学会大会  2017.11 

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    Event date: 2017.11

    Language:Japanese  

    Venue:東京   Country:Japan  

  • One-Pot Synthesis of Dual Stimulus-Responsive Degradable Organic-Inorganic Hybrid Hollow Nanoparticles for Fluorescence Image-Guided Trimodal Therapy Invited International conference

    Koichiro Hayashi

    BIT’s 7th Annual World Congress of Nano Science & Technology 2017  2017.10 

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    Event date: 2017.10

    Language:English  

    Venue:Fukuoka   Country:Japan  

  • One-Pot Synthesis of Organic-Inorganic Hybrid Hollow Nanoparticles for Fluorescence Image-Guided Trimodal Therapy Invited International conference

    Koichiro Hayashi

    2nd International Symposium on Creation of Life Innovation Materials for Interdisciplinary and International Researcher Development  2017.9 

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    Event date: 2017.9 - 2017.10

    Language:English  

    Venue:Nagoya   Country:Japan  

  • 多機能ナノ/マイクロ粒子の合成と診断・治療への応用 Invited

    林 幸壱朗

    第7回ナノカーボンバイオシンポジウム  2017.9 

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    Event date: 2017.9

    Language:Japanese  

    Venue:京都   Country:Japan  

  • 多機能性ナノ・マイクロ粒子の作製と生物医学応用 Invited

    林 幸壱朗

    日本ゾル-ゲル学会第15回討論会  2017.8 

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    Event date: 2017.8

    Language:Japanese  

    Venue:大阪   Country:Japan  

  • 骨軟骨再生を目指した細胞・マテリアル研究 炭酸アパタイト人工骨の構造・形状制御による骨再生増強と新機能発現

    林 幸壱朗

    日本骨代謝学会学術集会プログラム抄録集  2023.7  (一社)日本骨代謝学会

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    Language:Japanese  

  • 炭酸アパタイトハニカム人工骨に搭載されたチャネルと微細孔が分節型骨欠損の再建に与える影響と相互作用について

    柴原 啓吾, 林 幸壱朗, 石川 邦夫, 中島 康晴

    日本整形外科学会雑誌  2022.9  (公社)日本整形外科学会

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  • 炭酸アパタイトハニカムスキャフォールドの人工造血幹細胞ニッチとしての応用可能性

    林 幸壱朗, 岸田 良, 土谷 享, 石川 邦夫

    日本バイオマテリアル学会大会予稿集  2022.11  日本バイオマテリアル学会

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  • 炭酸アパタイトセメントの創製およびin vivo骨伝導性評価

    岸田 良, 林 幸壱朗, 土谷 享, 島袋 将弥, 石川 邦夫

    日本歯科理工学会誌  2022.5  (一社)日本歯科理工学会

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    Language:Japanese  

  • 抗菌性ハニカム人工骨の開発 Invited

    林 幸壱朗

    第42回整形外科バイオマテリアル研究会  2023.12 

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  • ポリ乳酸インプラントにおける炭酸含有アパタイトの分散状態がosseointegrationに及ぼす影響(Effects of carbonate apatite dispersion state in polylactic acid implants on osseointegration)

    Zhang Cheng, Hayashi Koichiro, Ishikawa Kunio

    日本歯科理工学会誌  2024.4  (一社)日本歯科理工学会

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    Language:English  

  • ポリエチレンテレフタレートの表面処理によるオッセオインテグレーションの付与

    土谷 享, 岸田 良, 林 幸壱朗, 石川 邦夫

    日本バイオマテリアル学会大会予稿集  2022.11  日本バイオマテリアル学会

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  • 軟骨再生用ハイドロゲル Invited

    林 幸壱朗

    JST 新技術説明会  2024.8 

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  • 炭酸アパタイトハニカムを用いた造血機能回復

    林 幸壱朗, 石川 邦夫

    第57回九大医工学連携イニシアチブ  2024.9 

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MISC

  • 【細胞の基礎と応用】造血幹細胞ニッチとして働き造血機能を回復する炭酸アパタイトハニカム材料

    林 幸壱朗

    バイオマテリアル-生体材料-   42 ( 1 )   76 - 81   2024.1   ISSN:1347-7080

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    Language:Japanese   Publisher:日本バイオマテリアル学会  

    造血幹細胞はすべての血液細胞の元であり,この幹細胞が異常をきたすと正常な造血が行われなくなり,血液がんや免疫不全症などの原因となる.これらの血液疾患を根治するために行われる造血幹細胞移植では,必要数の造血幹細胞の確保が不可欠であるが,現状では必ずしも確保できていない.造血幹細胞を維持・調節する微小環境(ニッチ)を人工的に創出することができれば,この問題を解決できると考えられる.本稿では,足場材料の構造と機能を活用した造血幹細胞ニッチの人工的創出と,その移植による造血機能の回復について述べる.(著者抄録)

  • 炭酸アパタイトハニカム人工骨に搭載されたチャネルと微細孔が分節型骨欠損の再建に与える影響と相互作用について

    柴原 啓吾, 林 幸壱朗, 石川 邦夫, 中島 康晴

    日本整形外科学会雑誌   96 ( 8 )   S1824 - S1824   2022.9   ISSN:0021-5325

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    Language:Japanese   Publisher:(公社)日本整形外科学会  

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  • 骨・骨髄再生および感染予防用ハニカムスキャフォールド —構造が拓く新機能― Reviewed

    @林幸壱朗

    セラミックス   2022.8

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • Honeycomb Scaffold: Effects of Microstructure on Bone Regeneration and Applications to Orthopedic and Dental Fields Reviewed

    @Koichiro Hayashi

    Journal of the Society of Powder Technology, Japan   2021.11

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    DOI: 10.4164/sptj.58.613

  • Carbonate apatite artificial bone Reviewed

    @Kunio Ishikawa,@Koichiro Hayashi

    Science and Technology of Advanced Materials   2021.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

    DOI: 10.1080/14686996.2021.1947120

  • 骨髄様組織を形成するハニカムスキャフォールド Reviewed

    @林 幸壱朗

    バイオインダストリー   2020.2

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  • 炭酸アパタイト顆粒の骨形成能評価 Reviewed

    @林幸壱朗, @石川邦夫

    バイオマテリアル-生体材料-   2019.4

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  • 磁場を使った医療技術

    @林 幸壱朗

    現代化学   2018.3

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  • 光と生体物質に応答する有機-無機ハイブリッド中空ナノ粒子の新規合成法とイメージガイド下三種同時治療

    @林 幸壱朗

    セラミックス   2017.3

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • Multifunctional Hybrid Nanoparticles for Biomedical Applications

    @Koichiro Hayashi

    Journal of the Ceramic Society of Japan   2016.9

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  • ナノ粒子を利用した温熱療法

    @林 幸壱朗

    医学のあゆみ   2015.1

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • マグネタイトナノ粒子クラスターの合成とMRIと磁気ハイパーサーミアを統合したセラノスティクスへの応用

    @林 幸壱朗

    セラミックス   2014.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

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Industrial property rights

Patent   Number of applications: 9   Number of registrations: 1
Utility model   Number of applications: 0   Number of registrations: 0
Design   Number of applications: 0   Number of registrations: 0
Trademark   Number of applications: 0   Number of registrations: 0

Professional Memberships

  • 日本バイオマテリアル学会

  • THE JAPANESE SOCIETY FOR DENTAL MATERIALS AND DEVICES

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  • The Ceramic Society of Japan

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Committee Memberships

  • バイオ関連材料デザイン研究会   代表  

    2024.4 - Present   

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  • The Ceramic Society of Japan   Local Organization Committee of ABC2024 (The 22nd Asian BioCeramics Symposium)  

    2024 - Present   

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    Committee type:Academic society

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  • 日本セラミックス協会 秋季シンポジウム   セッションオーガナイザー  

    2023 - Present   

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  • 日本セラミックス協会   第36回秋季シンポジウム特性セッションオーガナイザー   Domestic

    2022.7 - 2023.9   

  • 日本歯科理工学会   広報委員  

    2022.4 - Present   

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    Committee type:Academic society

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  • 日本バイオマテリアル学会   評議員  

    2022.4 - Present   

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    Committee type:Academic society

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  • 日本歯科理工学会   広報委員   Domestic

    2022.4 - 2024.3   

  • バイオ関連材料デザイン研究会   世話人   Domestic

    2020.4 - 2024.3   

  • 日本セラミックス協会   出版委員   Domestic

    2019.4 - 2021.3   

  • 日本歯科理工学会   代議員  

    2018.4 - Present   

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    Committee type:Academic society

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  • 日本歯科理工学会   Councilor   Domestic

    2018.4 - 2022.6   

  • 日本歯科理工学会   代議員   Domestic

    2018.4 - 2022.6   

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Academic Activities

  • 特定セッションオーガナイザー

    日本セラミックス協会 秋季シンポジウム 第37回秋期シンポジウム  ( Japan ) 2024.9

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    Type:Competition, symposium, etc. 

  • 代表

    バイオ関連材料デザイン研究会  ( Japan ) 2024.4 - 2029.3

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    Type:Competition, symposium, etc. 

  • 特定セッションオーガナイザー

    日本セラミックス協会 第36回秋季シンポジウム  ( Japan ) 2023.9

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    Type:Competition, symposium, etc. 

  • 日本セラミックス協会

    2019.5 - 2021.5

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    Type:Academic society, research group, etc. 

Research Projects

  • 日本医療研究開発機構(AMED)軟骨再生用ハイドロゲルの開発

    2024.4 - 2026.3

    日本医療研究開発機構(AMED)橋渡し研究戦略的推進プログラム シーズA

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    Authorship:Principal investigator  Grant type:Contract research

  • 骨粗鬆症の悪環境を逆手に取って治療するハニカム人工骨の開発

    Grant number:23K18593  2023 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Challenging Research(Exploratory)

    林 幸壱朗

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    Authorship:Principal investigator  Grant type:Scientific research funding

    世界的な高齢化に伴い、骨粗鬆症の患者が急増している。骨粗鬆症になると、骨の量と強度が減少し、転倒やくしゃみといった僅かな衝撃でも骨折してしまう。さらに、骨粗鬆症による骨折が原因で寝たきりになり、認知症につながることも知られている。骨粗鬆症の治療では、毎日や毎週の服薬を数年間継続する必要があり、患者の5割は、1年後には処方通りの服薬ができていない。このため、多くの患者において症状が改善せず、背骨や大腿骨の骨折や圧潰が繰り返し生じ、歩行困難や寝たきり、要介護となる。この問題を解決するために、本研究では、服薬を必要としない革新的治療を導く新規材料を開発する。

    CiNii Research

  • 日本医療研究開発機構(AMED) 抗菌性人工骨に関する非臨床POC取得

    2022.9 - 2025.3

    国立研究開発法人日本医療研究開発機構(AMED) 革新的医療技術創出拠点プロジェクト

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    Authorship:Principal investigator  Grant type:Contract research

  • Honeycomb bone scaffolds for bone marrow regeneration

    Grant number:23K25208  2022.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    林 幸壱朗

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    Grant type:Scientific research funding

    造血幹細胞の自己複製には造血幹細胞ニッチと呼ばれる微小空間が重要な役割を担っていること、造血幹細胞ニッチは骨内膜近傍に存在することが知られている。申請者は、造血幹細胞を自己複製している造血幹細胞ニッチに学び、骨内膜を裏打ちする骨の化学組成及び構造を模倣したスキャフォールドを作製した。ウサギ骨および筋肉内に移植したところ、骨内膜様組織が形成され、その中に骨髄様組織が維持されることを見出した。すなわち、スキャフォールド内に人工造血幹細胞ニッチが形成された。そこで本研究では、炭酸アパタイトハニカム材料が、造血幹細胞ニッチとして働き、造血機能を回復させることができるかを検証する。

    CiNii Research

  • 骨組成ハニカムスキャフォールドを用いた人工造血幹細胞ニッチの作製

    Grant number:22H03954  2022 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 国際学術論文掲載料(APC)支援

    2022

    全学共通課題対応等経費

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    Authorship:Principal investigator  Grant type:On-campus funds, funds, etc.

  • 日本医療研究開発機構(AMED) 術後感染を防ぐハニカム骨補填材の開発

    2020.9 - 2022.3

    日本医療研究開発機構(AMED) 官民による若手研究者発掘支援事業

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    Authorship:Principal investigator  Grant type:Contract research

  • 国立研究開発法人日本医療研究開発機構(AMED) 橋渡し研究戦略的推進プログラム シーズB 「自家骨採取は不要:炭酸アパタイト人工骨による骨再生」

    2020.4 - 2022.3

    国立研究開発法人日本医療研究開発機構(AMED) 

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  • 基盤研究(C) 「メタロキサンユニット含有中温域燃料電池用ハイブリッド膜の開発」

    2020.4 - 2021.3

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    Authorship:Coinvestigator(s) 

  • ハニカム細胞足場材料を用いた骨誘導現象の解明

    2020

    令和2年度QRプログラム

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    Authorship:Principal investigator  Grant type:On-campus funds, funds, etc.

  • ハニカムスキャフォールドの筋肉内組織形成挙動の組織学的評価

    2020

    令和2年度九州大学大学院歯学研究院科学研究費助成事業 再チャレンジ支援プログラム

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    Authorship:Principal investigator  Grant type:On-campus funds, funds, etc.

  • Establishment of nanocarrier platform by cell membrane modification for diagnosis and treatment of urological cancers

    Grant number:19K22684  2019.6 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Hayashi Akinobu

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    Grant type:Scientific research funding

    In the background of a proposal for a therapeutic method using nanomaterials, especially superparamagnetic iron oxide (SPIO), we aimed to fabricate novel nanocarriers for diagnosis and treatment with nanoparticles as the core by utilizing biological membranes (cell membranes) of urological tumor cells (prostate cancer, urothelial carcinoma, renal cancer) and other cells. We attempted (1) synthesis of nanocarriers using self-assembly of ruptured cell membranes and (2) method using physiological processes inherent to cells (nanoparticles taken into cells by exposure to nanoparticles are discharged in the form of exosomes). Although the methods being difficult, we succeeded in producing nanoparticles covered by cell membranes and found the possibility of increasing cellular uptake.

    CiNii Research

  • 挑戦的研究(萌芽) 「炭酸アパタイトハニカムの微細構造制御による骨誘導能付与と骨再建」

    2019.6 - 2022.3

    JSPS 

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    Authorship:Principal investigator 

  • 挑戦的研究(萌芽)「泌尿器腫瘍の診断・治療のための生体膜修飾で拓くナノキャリアのプラットホーム作製」

    2019.4 - 2022.3

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    Authorship:Coinvestigator(s) 

  • 泌尿器腫瘍の診断・治療のための生体膜修飾で拓くナノキャリアのプラットホーム作製

    2019 - 2021

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Challenging Research(Exploratory)

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    Authorship:Coinvestigator(s)  Grant type:Scientific research funding

  • 炭酸アパタイトハニカムの微細構造制御による骨誘導能付与と骨再建

    Grant number:19K22970  2019 - 2021

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Challenging Research(Exploratory)

    林 幸壱朗

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    Authorship:Principal investigator  Grant type:Scientific research funding

    申請者は骨と同じ組成(炭酸アパタイト)から成り、一次元に連通した細孔を有するブロック(ハニカム)を作製してきた。この炭酸アパタイトハニカムの細孔内には血管と骨が形成され、自家骨に匹敵する高い骨伝導能を示すことを動物実験により明らかにしている。上記の予備実験結果から、ハニカムのようなセラミックスの微細構造制御により、骨誘導能を付与できる可能性があると考えるに至った。そこで本研究は、炭酸アパタイトハニカムをベースとして、骨誘導能を有する新規材料の開発を試みる。

    CiNii Research

  • 国立研究開発法人日本医療研究開発機構(AMED) 橋渡し研究戦略的推進プログラム シーズB 「自家骨採取は不要:炭酸アパタイト骨置換材による骨再生」

    2018.10 - 2019.3

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    Authorship:Coinvestigator(s) 

  • 厚生労働科学研究費補助金「生体影響予測を基盤としたナノマテリアル の統合的健康影響評価方法の提案」

    2018.4 - 2021.3

    厚生労働省 

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    Authorship:Coinvestigator(s) 

  • 生体影響予測を基盤としたナノマテリアル の統合的健康影響評価方法の提案

    2018 - 2020

    Grants-in-Aid for Scientific Research  Grants-in-Aid for Scientific Research (Ministry of Health, Labour and Welfare)

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    Authorship:Coinvestigator(s)  Grant type:Competitive funding other than Grants-in-Aid for Scientific Research

  • 生体影響予測を基盤としたナノマテリアルの統合的健康影響評価方法の提案

    2018 - 2020

    Grants-in-Aid for Scientific Research (Ministry of Health, Labour and Welfare)

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    Authorship:Coinvestigator(s)  Grant type:Contract research

  • 国立研究開発法人日本医療研究開発機構(AMED) 橋渡し研究戦略的推進プログラム シーズB「自家骨採取は不要:炭酸アパタイト骨置換材による骨再生」

    2018

    国立研究開発法人日本医療研究開発機構(AMED) 橋渡し研究戦略的推進プログラム シーズB

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    Authorship:Coinvestigator(s)  Grant type:Contract research

  • 基盤研究(B)「肝硬変治療の為の多機能性有機-無機ハイブリッドナノ粒子の開発」

    2017.4 - 2020.3

    日本学術振興会 

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    Authorship:Principal investigator 

  • 肝硬変治療の為の多機能性有機-無機ハイブリッドナノ粒子の開発

    2017 - 2019

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • シームレス蛍光イメージングに資する有機・無機ハイブリッドナノ粒子の合成

    2016 - 2017

    文部科学省「学際・国際的高度人材育成ライフイノベーションマテリアル創製共同研究プロジェクト」

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    Authorship:Principal investigator  Grant type:Contract research

  • 「腫瘍内で瞬時にゲル化する磁性流体」の開発による局所化学療法と磁気温熱療法の実現

    2015 - 2017

    Grants-in-Aid for Scientific Research  Grant-in-Aid for challenging Exploratory Research

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 新規in vitro評価系およびマーカーの開発によるナノマテリアルのリスク評価及びリスク低減化に関する研究

    2015 - 2017

    Grants-in-Aid for Scientific Research  Grants-in-Aid for Scientific Research (Ministry of Health, Labour and Welfare)

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    Authorship:Coinvestigator(s)  Grant type:Competitive funding other than Grants-in-Aid for Scientific Research

  • ナノマテリアルの遺伝毒性メカニズムに基づいた新規in vitro遺伝毒性評価系システムの構築

    2015 - 2016

    一般社団法人日本化学工業協会 新LRI(The Long-range Research Initiative)

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    Authorship:Coinvestigator(s)  Grant type:Contract research

  • 磁性ナノ粒子のクラスター化により発熱量が向上する理由の解明と磁気温熱療法への展開

    2015

    公益財団法人加藤科学振興会研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • In vivoおよびin vitro蛍光イメージング用プローブの開発

    2014.10 - 2016.2

    Research commissions

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    Authorship:Principal investigator  Grant type:Other funds from industry-academia collaboration

  • 磁場応答性ナノ粒子の開発と「磁気温熱療法と薬剤治療の一体化」による治療効果増強

    2014 - 2016

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (A)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 蛍光in vivoイメージャー用蛍光プローブの開発

    2013.11 - 2014.3

    Research commissions

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    Authorship:Principal investigator  Grant type:Other funds from industry-academia collaboration

  • 発熱量が大きい磁性ナノ粒子の開発と磁気ハイパーサーミアを利用した腫瘍ターゲティングの促進

    2013

    JST研究成果展開事業 研究成果最適展開支援プログラムA-STEPフィージビリティスタディステージ

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    Authorship:Principal investigator  Grant type:Contract research

  • 戦略的イノベーション創出推進プログラム「革新的硬組織再生・再建システム創製」

    2012.11 - 2019.3

    独立行政法人科学技術振興機構 

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    Authorship:Coinvestigator(s) 

  • 癌の画像診断・温熱治療への応用を目的とした磁性ナノ粒子の創製

    2012 - 2013

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • TiO2階層構造体の化粧品・光触媒・色素増感太陽電池への応用

    2011

    JST「知財活用促進ハイウェイ」大学特許価値向上支援

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    Authorship:Principal investigator  Grant type:Contract research

  • 生理的条件下で合成した花型酸化チタンナノ粒子の光触媒活性

    2011

    財団法人日本科学協会 笹川科学研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • Multifunctional superparamagnetic nanoparticle/organic hybrid for simultaneous diagnosis and treatment

    2010

    一般財団法人 丸文財団 国際交流助成

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    Authorship:Principal investigator  Grant type:Contract research

  • ガン選択性を有する磁性ナノ粒子の開発と温熱治療への応用

    2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for JSPS Fellows

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    Authorship:Principal investigator  Grant type:Scientific research funding

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Educational Activities

  • 歯科理工学に関する教育及び大学院生への学位論文研究指導

Award for Educational Activities

  • Best teacher of the year 2012

       

Class subject

  • リサーチエクスポージャー

    2024.10 - 2025.3   Second semester

  • 歯学概論

    2024.4 - 2025.3   Full year

  • 歯学総論

    2024.4 - 2025.3   Full year

  • アーリーエクスポージャー

    2024.4 - 2024.9   First semester

  • 歯科理工学

    2023.4 - 2024.3   Full year

  • 生体材料学

    2023.4 - 2024.3   Full year

  • Biomaterials

    2023.4 - 2024.3   Full year

  • 生体材料学

    2022.4 - 2023.3   Full year

  • 歯科理工学

    2022.4 - 2023.3   Full year

  • Biomaterials

    2022.4 - 2023.3   Full year

  • リサーチエクスポージャー

    2022.4 - 2022.9   First semester

  • 歯学総論

    2021.10 - 2022.3   Second semester

  • リサーチエクスポージャー

    2021.4 - 2022.3   Full year

  • 生体材料学演習

    2021.4 - 2022.3   Full year

  • Biomaterials

    2021.4 - 2022.3   Full year

  • 歯科理工学

    2021.4 - 2022.3   Full year

  • 歯学概論

    2021.4 - 2021.9   First semester

  • アーリーエクスポージャー

    2021.4 - 2021.9   First semester

  • 生体材料学演習

    2020.4 - 2021.3   Full year

  • 歯科理工学

    2020.4 - 2021.3   Full year

  • Biomaterials

    2020.4 - 2021.3   Full year

  • Biomaterials

    2019.4 - 2020.3   Full year

  • 歯科理工学

    2019.4 - 2020.3   Full year

  • 生体材料学演習

    2019.4 - 2020.3   Full year

  • リサーチエクスポージャー

    2019.4 - 2019.9   First semester

  • 総合歯科学

    2018.10 - 2019.3   Second semester

  • 歯科理工学

    2018.4 - 2019.3   Full year

  • リサーチエクスポージャー

    2018.4 - 2019.3   Full year

  • 生体材料学演習

    2018.4 - 2019.3   Full year

  • 生体材料学

    2018.4 - 2019.3   Full year

  • Biomaterials

    2018.4 - 2019.3   Full year

  • アーリーエクスポージャー

    2018.4 - 2018.9   First semester

  • 歯科理工学

    2017.4 - 2018.3   Full year

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Visiting, concurrent, or part-time lecturers at other universities, institutions, etc.

  • 2020  三重大学大学医学系研究科   Classification:Affiliate faculty  Domestic/International Classification:Japan 

Other educational activity and Special note

  • 2024  Special Affairs  CBT作問委員

     詳細を見る

    CBT作問委員

Outline of Social Contribution and International Cooperation activities

  • Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia (PMDSU scholarship grant no. 2190/UN1/DITLIT/Dit-Lit/PT.01.03/2023)
    Ministry of Education, Culture, Research, and Technology of the Republic of Indonesia (PKPI-PMDSU 2023 program)
    公益社団法人日本化学会 化学グランプリ・オリンピック委員会 二次選考運営委員(共催:JST, 高等学校文化連盟全国自然科学専門部, 後援:文部科学省, 経済産業省) 2016年
    JST次世代人材育成事業グローバルサイエンスキャンパス 平成28年度名古屋大学内委員(高大接続事業)2016年
    名古屋大学工学部テクノサイエンスセミナー/化学・生物実験講習会 平成27年度学内委員(高大接続事業)2015年
    愛知県産業技術センター勉強会 講師 2015年
    公益社団法人日本セラミックス協会 国際交流委員 2010年

Media Coverage

  • インプラント向け人工骨補填材 ハニカムで形成倍速

    日刊工業新聞  2021.8

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    インプラント向け人工骨補填材 ハニカムで形成倍速

  • 人工骨組織から「骨髄」組織 九大、白血病治療などに応用も Newspaper, magazine

    日経産業新聞  2019.4

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    人工骨組織から「骨髄」組織 九大、白血病治療などに応用も

  • 赤血球状の粒子 肝臓に薬剤運搬 Newspaper, magazine

    日経産業新聞  2017.12

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    赤血球状の粒子 肝臓に薬剤運搬

  • 新ナノ粒子でがん狙い撃ち Newspaper, magazine

    中日新聞  2016.12

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    新ナノ粒子でがん狙い撃ち

  • スマートナノ粒子 がん治療効果高める 名大が開発 腫瘍狙い局所加熱 Newspaper, magazine

    化学工業日報  2014.8

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    スマートナノ粒子 がん治療効果高める 名大が開発 腫瘍狙い局所加熱