研究者詳細 - HARA EMILIO SATOSHI

論文 - HARA EMILIO SATOSHI

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The cell membrane as biofunctional material for accelerated bone repair. 査読国際誌

Emi Hatano, Nahid Akhter, Risa Anada, Mitsuaki Ono, Toshitaka Oohashi, Takuo Kuboki, Hiroshi Kamioka, Masahiro Okada, Takuya Matsumoto, Emilio Satoshi Hara

Acta biomaterialia 2024年7月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The cell (plasma) membrane is enriched with numerous receptors, ligands, enzymes, and phospholipids that play important roles in cell-cell and cell-extracellular matrix interactions governing, for instance, tissue development and repair. We previously showed that plasma membrane nanofragments (PMNFs) act as nucleation sites for bone formation in vivo, and induce in vitro mineralization within 1 day. In this study, we optimized the methods for generating, isolating, and applying PMNFs as a cell-free therapeutic to expedite bone defect repair. The PMNFs were isolated from different mouse cell lines (chondrocytes, osteoblasts, and fibroblasts), pre-conditioned, lyophilized, and subsequently transplanted into 2 mm critical-sized calvarial defects in mice (n = 75). The PMNFs from chondrocytes, following a 3-day pre-incubation, significantly accelerated bone repair within 2 weeks, through a coordinated attraction of macrophages, endothelial cells, and osteoblasts to the healing site. In vitro experiments confirmed that PMNFs enhanced cell adhesion. Comparison of the PMNF efficacy with phosphatidylserine, amorphous calcium phosphate (ACP), and living cells confirmed the unique ability of PMNFs to promote accelerated bone repair. Importantly, PMNFs promoted nearly complete integration of the regenerated bone with native tissue after 6 weeks (% non-integrated bone area = 15.02), contrasting with the partial integration (% non-integrated bone area = 56.10; p < 0.01, Student's test) with transplantation of ACP. Vickers microhardness tests demonstrated that the regenerated bone after 6 weeks (30.10 ± 1.75) exhibited hardness similar to native bone (31.07 ± 2.46). In conclusion, this is the first study to demonstrate that cell membrane can be a promising cell-free material with multifaceted biofunctional properties that promote accelerated bone repair. STATEMENT OF SIGNIFICANCE.

DOI： 10.1016/j.actbio.2024.07.037

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Re-Evaluation of Initial Bone Mineralization from an Engineering Perspective 査読国際誌

Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takayoshi Nakano, Takuya Matsumoto

Tissue Engineering Part B: Reviews 28 ( 1 ) 246 - 255 2022年2月

Biohybrid Variable‐Stiffness Soft Actuators that Self‐Create Bone 査読

Danfeng Cao, Jose G. Martinez, Emilio Satoshi Hara, Edwin W. H. Jager

Advanced Materials 34 ( 8 ) 2107345 - 2107345 2022年2月

Effect of Biomechanical Environment on Degeneration of Meckel’s Cartilage 査読

Mahmoud Farahat, Gulsan A.S. Kazi, Emilio S. Hara, Takuya Matsumoto

Journal of Dental Research 100 ( 2 ) 171 - 178 2021年2月

Bone Marrow Cells Inhibit BMP‐2‐Induced Osteoblast Activity in the Marrow Environment 査読

Ha Thi Nguyen, Mitsuaki Ono, Yasutaka Oida, Emilio Satoshi Hara, Taishi Komori, Kentaro Akiyama, Ha Thi Thu Nguyen, Kyaw Thu Aung, Hai Thanh Pham, Ikue Tosa, Takeshi Takarada, Koichi Matsuo, Toshihide Mizoguchi, Toshitaka Oohashi, Takuo Kuboki

Journal of Bone and Mineral Research 34 ( 2 ) 327 - 332 2019年2月

Rapid bioinspired mineralization using cell membrane nanofragments and alkaline milieu 査読

Emilio Satoshi Hara, Masahiro Okada, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

Journal of Materials Chemistry B 6 ( 38 ) 6153 - 6161 2018年9月

Bioinspired Mineralization Using Chondrocyte Membrane Nanofragments 査読国際誌

Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takako Hattori, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

ACS Biomaterials Science & Engineering 4 ( 2 ) 617 - 625 2018年2月

Biocompatible nanostructured solid adhesives for biological soft tissues 査読

Masahiro Okada, Akira Nakai, Emilio Satoshi Hara, Tetsushi Taguchi, Takayoshi Nakano, Takuya Matsumoto

Acta Biomaterialia 57 404 - 413 2017年

Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF‐β3–Associated Chondrogenesis of Bone Marrow–Derived Mesenchymal Stem Cells for Articular Surface Regeneration 査読

Emilio Satoshi Hara, Mitsuaki Ono, Hai Thanh Pham, Wataru Sonoyama, Satoshi Kubota, Masaharu Takigawa, Takuya Matsumoto, Marian F Young, Bjorn R Olsen, Takuo Kuboki

Journal of Bone and Mineral Research 30 ( 9 ) 1585 - 1596 2015年9月

Novel chondrogenic and chondroprotective effects of the natural compound harmine 査読

Emilio Satoshi Hara, Mitsuaki Ono, Satoshi Kubota, Wataru Sonoyama, Yasutaka Oida, Takako Hattori, Takashi Nishida, Takayuki Furumatsu, Toshifumi Ozaki, Masaharu Takigawa, Takuo Kuboki

Biochimie 95 ( 2 ) 374 - 381 2013年2月

BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells

Ikue Tosa, Mitsuaki Ono, Anh Tuan Dang, Ziyi Wang, Maiko Kimura, Wakana Kitagawa, Kei Ishibashi, Hang Thuy Do, Kun Zhao, Emilio Satoshi Hara, Noboru Asada, Takashi Nagasawa, Toshitaka Oohashi, Naoya Ohara, Takuo Kuboki

Blood Advances 2025年3月

Local E-rhBMP-2/β-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model 査読

Anh Tuan Dang, Mitsuaki Ono, Ziyi Wang, Ikue Tosa, Emilio Satoshi Hara, Akihiro Mikai, Wakana Kitagawa, Tomoko Yonezawa, Takuo Kuboki, Toshitaka Oohashi

International Journal of Molecular Sciences 25 ( 12 ) 6648 - 6648 2024年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.

DOI： 10.3390/ijms25126648

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Electrochemical control of bone microstructure on electroactive surfaces for modulation of stem cells and bone tissue engineering 査読国際誌

Danfeng Cao, Jose G. Martinez, Risa Anada, Emilio Satoshi Hara, Hiroshi Kamioka, Edwin W. H. Jager

Science and Technology of Advanced Materials 24 ( 1 ) 2183710 - 2183710 2023年12月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Controlling stem cell behavior at the material interface is crucial for the development of novel technologies in stem cell biology and regenerative medicine. The composition and presentation of bio-factors on a surface strongly influence the activity of stem cells. Herein, we designed an electroactive surface that mimics the initial process of trabecular bone formation, by immobilizing chondrocyte-derived plasma membrane nanofragments (PMNFs) on its surface for rapid mineralization within 2 days. Moreover, the electroactive surface was based on the conducting polymer polypyrrole (PPy), which enabled dynamic control of the presentation of PMNFs on the surface via electrochemical redox switching, further resulting in the formation of bone minerals with different morphologies. Furthermore, bone minerals with contrasting surface morphologies had differential effects on the differentiation of human bone marrow-derived stem cells (hBMSCs) cultured on the surface. Together, this electroactive surface showed multifunctional characteristics, not only allowing dynamic control of PMNF presentation but also promoting the formation of bone minerals with different morphologies within 2 days. This electroactive substrate could be valuable for more precise control of stem cell growth and differentiation, and further development of more suitable microenvironments containing bone apatite for housing a bone marrow stem cell niche, such as biochips/bone-on-chips.

DOI： 10.1080/14686996.2023.2183710

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Tunable electroactive biomimetic bone-like surfaces for bone marrow-on-chips 査読

Danfeng Cao, Jose G. Martinez, Laetitia Skalla, Erik Hultin, Jan-Ingvar Jönsson, Risa Anada, Hiroshi Kamioka, Edwin W. H. Jager, Emilio Satoshi Hara

2023 IEEE BioSensors Conference (BioSensors) 1 - 4 2023年7月

Variable Stiffness Actuators with Covalently Attached Nanofragments that Induce Mineralization 査読国際誌

Danfeng Cao, Jose G. Martinez, Emilio Satoshi Hara, Edwin W. H. Jager

Advanced Materials Technologies 2201651 - 2201651 2023年4月

Important roles of odontoblast membrane phospholipids in early dentin mineralization 査読国際誌

Risa Anada, Emilio Satoshi Hara, Noriyuki Nagaoka, Masahiro Okada, Hiroshi Kamioka, Takuya Matsumoto

Journal of Materials Chemistry B 11 ( 3 ) 657 - 666 2023年1月

Fabrication of initial trabecular bone inspired three-dimensional structure with cell membrane nanofragments 査読

Koichi Kadoya, Emilio Satoshi Hara, Masahiro Okada, YuYang Jiao, Takayoshi Nakano, Akira Sasaki, Takuya Matsumoto

2022年11月

Distinct Morphologies of Bone Apatite Clusters in Endochondral and Intramembranous Ossification 査読

Emilio Satoshi Hara, Noriyuki Nagaoka, Masahiro Okada, Takayoshi Nakano, Takuya Matsumoto

Advanced Biology 6 ( 11 ) 2200076 - 2200076 2022年11月

Soft actuators that self-create bone for biohybrid (micro)robotics 査読

Danfeng Cao, Jose G. Martinez, Emilio Satoshi Hara, Edwin W. H. Jager

2022 International Conference on Manipulation, Automation and Robotics at Small Scales (MARSS) 2022年7月

Mechanotransductive Mechanisms of Biomimetic Hydrogel Cues Modulating Meckel's Cartilage Degeneration 査読

Mahmoud Farahat, Emilio S. Hara, Risa Anada, Gulsan A.S. Kazi, Nahid M. Akhter, Takuya Matsumoto

Advanced Biology 2101315 - 2101315 2022年6月

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