Development of Cell Delivery Carrier Consisting of Free-standing Polymer Nanosheets

• Project/Area Number: 25870050
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering; Polymer chemistry
• Research Institution: Waseda University
• Principal Investigator: FUJIE Toshinori 早稲田大学, 理工学術院, 助教 (70538735)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ナノバイオ材料 / 生体材料科学 / 生体組織工学 / 再生医療 / 細胞移植 / 加齢黄斑変性症 / 高分子超薄膜 / 微細加工技術 / 生体材料 / 細胞移植療法 / 網膜色素上皮細胞 / 高分子ナノ薄膜 / ナノシート / 微細加工 / 移植・再生医療 / ナノバイオ / 細胞デリバリー

Outline of Final Research Achievements

For the treatment of intractable retinal diseases such as age-related macular degeneration, in this study we envisioned development of a cell delivery carrier using flexible polymer nanosheets to transplant retinal pigment epithelial cells into a narrow subretinal place. Micropatterned nanosheets were fabricated from poly(lactic-co-glycolic acid), on which the cells were selectively cultured. It was clarified that the engineered cell monolayer on the micropatterned nanosheet was aspirated and injected through a clinical needle without loss of cell viability (approximately 90% viable). The cell monolayer was also transplanted to the subretinal place of rats near the macula. Overall, for the first time we demonstrated the utility of nanosheets in cell delivery system.

Research Products

• [Journal Article] Spatial coordination of cell orientation directed by unique nanoribbon sheets. (2015)
  • Author(s): Fujie, T., Shi, X., Ostrovidov, S., Liang, X., Nakajima, K., Chen, Y., Wu, H., Khademhosseini, A.
  • Journal Title: Biomaterials Volume: 53 Pages: 86-94
  • DOI: 10.1016/j.biomaterials.2015.02.028
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Three-dimensional co-culture of C2C12/PC12 cells improves skeletal muscle tissue formation and function. (2014)
  • Author(s): Ostrovidov, S., Ahadian, S., Ramon-Azcon, J., Hosseini, V., Fujie, T., Prakash Parthiban, S., Shiku, H., Matsue, T., Kaji, H., Ramalingam, M., Bae, H., Khademhosseini, A.
  • Journal Title: Journal of Tissue Engineering and Regenerative Medicine Volume: - Issue: 2 Pages: 582-595
  • DOI: 10.1002/term.1956
  • Peer Reviewed
• [Journal Article] Myotube formation on gelatin nanofibers - multiwalled carbon nanotubes hybrid scaffolds. (2014)
  • Author(s): Ostrovidov, S., Shi, X., Zhang, L., Liang, X., Kim, S-B., Fujie, T., Ramalingam, M., Chen, M., Nakajima, K., Al-Hazmi, F., Bae, H., Memic, A., Khademhosseini, A.
  • Journal Title: Biomaterials Volume: 35 Issue: 24 Pages: 6268-6277
  • DOI: 10.1016/j.biomaterials.2014.04.021
  • Peer Reviewed
• [Journal Article] Periosteum-mimetic structures made from freestanding microgrooved nanosheets. (2014)
  • Author(s): Shi, X., Fujie, T., Saito, A., Takeoka, S., Hou, Y., Shu, Y., Chen, M., Wu, H., Khademhosseini, A.
  • Journal Title: Advanced Materials Volume: 26 Issue: 20 Pages: 3290-3296
  • DOI: 10.1002/adma.201305804
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Skeletal muscle tissue engineering: Methods to form skeletal myotubes and their applications (2014)
  • Author(s): Serge Ostrovidov, Vahid Hosseini, Samad Ahadian, Toshinori Fujie, S. Prakash Parthiban, Murugan Ramalingam, Hojae Bae, Hirokazu Kaji, Ali Khademhosseini
  • Journal Title: Tissue Eng. B Volume: (in press) Issue: 5 Pages: 403-436
  • DOI: 10.1089/ten.teb.2013.0534
  • Peer Reviewed
• [Journal Article] Development of Polymer Nanosheets Inspired by Extracellular Matrix Towards Tissue Engineering Applications (2014)
  • Author(s): 藤枝 俊宣
  • Journal Title: KOBUNSHI RONBUNSHU Volume: 71 Issue: 9 Pages: 408-417
  • DOI: 10.1295/koron.71.408
  • NAID: 130004691183
  • ISSN: 0386-2186, 1881-5685
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 再生医療を指向したバイオニックナノ薄膜の創製 (2014)
  • Author(s): 藤枝 俊宣
  • Journal Title: 化学と工業 Volume: 67 Pages: 996-997
  • Peer Reviewed
• [Journal Article] Micropatterned polymeric nanosheets for local delivery of an engineered epithelial monolayer (2014)
  • Author(s): Fujie, T., Mori, Y., Ito, S., Nishizawa, M., Bae, H., Nagai, N., Onami, H., Abe, T., Khademhosseini, A., Kaji, H.
  • Journal Title: Advanced Materials Volume: 26 Issue: 11 Pages: 1699-1705
  • DOI: 10.1002/adma.201304183
  • Peer Reviewed
• [Journal Article] 低侵襲な細胞移植療法に向けた微細パターン化高分子ナノシートの開発 (2014)
  • Author(s): 藤枝 俊宣
  • Journal Title: バイオマテリアル-生体材料- Volume: 32(1) Pages: 35-38
• [Journal Article] ナノシートを活かした新しい医療材料：ナノ絆創膏の開発 (2014)
  • Author(s): 藤枝 俊宣
  • Journal Title: バイオサイエンスとインダストリー Volume: 72(2) Pages: 127-129
  • NAID: 40020020653
• [Journal Article] 細胞外マトリックスの構造と機能を規範とする高分子ナノシートの開発と組織工学への応用 (2014)
  • Author(s): 藤枝 俊宣
  • Journal Title: 機能材料 Volume: 34(1) Pages: 32-39
• [Journal Article] Engineered nanomembranes for directing cellular organization towards flexible biodevices (2013)
  • Author(s): Toshinori Fujie, Samad Ahadian, Hao Liu, Haixin Chang, Serge Ostrovidov, Hongkai Wu, Hojae Bae, Ken Nakajima, Hirokazu Kaji, Ali Khademhosseini
  • Journal Title: Nano Lett. Volume: 13 Issue: 7 Pages: 3185-3192
  • DOI: 10.1021/nl401237s
  • Peer Reviewed
• [Journal Article] Engineered nanomembranes for directing cellular organization towards flexible biodevices (2013)
  • Author(s): Fujie, T., Ahadian, S., Liu, H., Chang, H., Ostrovidov, S., Wu, H., Bae, H., Nakajima, K., Kaji, H., Khademhosseini, A.
  • Journal Title: Nano Letters Volume: 13 Issue: 8 Pages: 3185-3192
  • DOI: 10.1002/jbm.a.34935
  • Peer Reviewed
• [Presentation] 導電性高分子ナノシートの構築とフレキシブル皮膚電極への応用 (2015)
  • Author(s): 藤枝 俊宣, 山岸 健人, 岡本 麻鈴, 武岡 真司.
  • Organizer: 日本化学会第95春季年会(2015)
  • Place of Presentation: 千葉
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 高分子ナノシート上への金属配線のインクジェット印刷 (2015)
  • Author(s): 岡本 麻鈴, 黒飛 みずほ, 山岸 健人, 村田 篤, 藤枝 俊宣, 岩瀬 英治, 岩田 浩康, 武岡 真司.
  • Organizer: 日本化学会第95春季年会(2015)
  • Place of Presentation: 千葉
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 高分子ブレンドを利用したナノシートからの薬物徐放制御 (2015)
  • Author(s): 西脇 圭亮，藤枝 俊宣，藤井 真央, 武岡 真司.
  • Organizer: 日本化学会第95春季年会(2015)
  • Place of Presentation: 千葉
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 生体適合性ナノシートにおけるシート形状制御 (2015)
  • Author(s): 新保 創太，藤枝 俊宣，岩瀬 英治.
  • Organizer: 日本機械学会 関東学生会第54回学生員卒業研究発表講演会
  • Place of Presentation: 神奈川
  • Year and Date: 2015-03-20
• [Presentation] 先端医療分野への応用を目指した高分子ナノシートの開発 (2015)
  • Author(s): 藤枝 俊宣.
  • Organizer: 帝人21世紀フォーラム
  • Place of Presentation: 静岡
  • Year and Date: 2015-01-10 – 2015-01-11
  • Invited
• [Presentation] Development of freestanding microgrooved nanosheets with periosteum-mimetic structure. (2014)
  • Author(s): Fujie, T., Shi, X., Ostrovidov, S., Wu, H., Khademhosseini, H., Takeoka, S.
  • Organizer: Materials Today Asia 2014
  • Place of Presentation: HongKong
  • Year and Date: 2014-12-09 – 2014-12-12
• [Presentation] 骨膜様微細溝構造を有する高分子ナノシートの開発 (2014)
  • Author(s): 藤枝 俊宣, Shi Xuetao, Ostrovidov Serge, 武岡 真司, Khademhosseini Ali.
  • Organizer: 第36回日本バイオマテリアル学会大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-17 – 2014-11-18
• [Presentation] ラット眼球網膜下への細胞担持ナノシートデリバリー (2014)
  • Author(s): 森 好弘, 藤枝 俊宣, 永井 展裕, 西澤 松彦, 阿部 俊明, 梶 弘和.
  • Organizer: 第36回日本バイオマテリアル学会大会
  • Place of Presentation: 東京
  • Year and Date: 2014-11-17 – 2014-11-18
• [Presentation] Flexible Skin-contact electrodes for recording biological electrical signals. (2014)
  • Author(s): Fujie, T.
  • Organizer: 2nd Symposium on the Institute of Advanced Active Aging, Waseda University
  • Place of Presentation: Tokyo
  • Year and Date: 2014-10-16 – 2014-10-17
  • Invited
• [Presentation] 導電性ナノシートの構築と皮膚電極としての特性評価 (2014)
  • Author(s): 山岸 健人, 藤枝 俊宣, 武岡 真司.
  • Organizer: 第4回CSJ化学フェスタ2014
  • Place of Presentation: 東京
  • Year and Date: 2014-10-14 – 2014-10-16
• [Presentation] Fabrication of Micropatterned Polymeric Nanosheets for Local Delivery of an Engineered Epithelial Monolayer. (2014)
  • Author(s): Fujie, T., Mori, Y., Nishizawa, M., Nagai, N., Abe, T., Khademhosseini, A., Kaji, H.
  • Organizer: JSPS A3 Foresight International Symposium on Nano-Biomaterials and Regenerative Medicine
  • Place of Presentation: Tokyo
  • Year and Date: 2014-10-08 – 2014-10-09
• [Presentation] Development of Hierarchical Cellular Organization from Ultra Thin Macroporous Poly(lactic acid) Films. (2014)
  • Author(s): Suzuki, S. Fujie, T., Takeoka, S.
  • Organizer: JSPS A3 Foresight International Symposium on Nano-Biomaterials and Regenerative Medicine
  • Place of Presentation: Tokyo
  • Year and Date: 2014-10-08 – 2014-10-09
• [Presentation] 微細加工技術を用いた高分子ナノシートの機能化と組織工学応用 (2014)
  • Author(s): 藤枝 俊宣, Shi Xuetao, Ostrovidov Serge, Khademhosseini Ali, 武岡 真司.
  • Organizer: 第63回高分子討論会
  • Place of Presentation: 長崎
  • Year and Date: 2014-09-24 – 2014-09-26
• [Presentation] 薬物担持ナノシートの構築と創傷被覆材としての評価 (2014)
  • Author(s): 武岡 真司, 伊藤 佳祐, 藤枝 俊宣, 木下 学, 宮崎 裕美, 斎藤 大蔵.
  • Organizer: 第63回高分子討論会
  • Place of Presentation: 長崎
  • Year and Date: 2014-09-24 – 2014-09-26
• [Presentation] Calix crown 誘導体からなる高分子ナノシートの構築 (2014)
  • Author(s): 佐藤 克典, 野口 元, 浅尾 幸平, 村田 篤, 藤枝 俊宣, 長瀬 裕, 武岡 真司.
  • Organizer: 第63回高分子討論会
  • Place of Presentation: 長崎
  • Year and Date: 2014-09-24 – 2014-09-26
• [Presentation] Bionic Nanomembranes Towards Wearable Electronics. (2014)
  • Author(s): Fujie, T.
  • Organizer: The 75th JSAP Annual Meeting 2014: Innovation in R&D of the Flexible Electronics -Toward the Inorganic Flexible Devices-
  • Place of Presentation: Sapporo
  • Year and Date: 2014-09-17 – 2014-09-20
  • Invited
• [Presentation] Engineered nanomembranes towards flexible bioelectronics. (2014)
  • Author(s): Fujie, T.
  • Organizer: The 15th Joint Symposium between the University of Bonn and Waseda University on ‘Metabolic Sensing: Biology and Nano-Medicine’.
  • Place of Presentation: Chiba
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] 皮膚電極に向けた導電性ナノシートの作製 (2014)
  • Author(s): 山岸 健人, 藤枝 俊宣, 武岡 真司.
  • Organizer: 第9回相模ケイ素・材料フォーラム
  • Place of Presentation: 神奈川
  • Year and Date: 2014-08-28
• [Presentation] Micropatterned polymeric nanosheets for local injection of an engineered epithelial monolayer. (2014)
  • Author(s): Fujie, T., Mori, Y., Nishizawa, M., Nagai, N., Abe, T., Khademhosseini, A., Kaji, H.
  • Organizer: 248th ACS National Meeting & Exposition
  • Place of Presentation: San Francisco
  • Year and Date: 2014-08-10 – 2014-08-14
• [Presentation] Fabrication and evaluation of free-standing macroporous poly(lactic acid) nanosheets. (2014)
  • Author(s): Suzuki, S., Fujie, T., Zhang, H., Takeoka, S.
  • Organizer: 248th ACS National Meeting & Exposition
  • Place of Presentation: San Francisco
  • Year and Date: 2014-08-10 – 2014-08-14
• [Presentation] 機能性高分子ナノシートの開発と生体組織工学への応用 (2014)
  • Author(s): 藤枝 俊宣.
  • Organizer: 14－1 超分子研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-14
  • Invited
• [Presentation] 高分子ナノシートからなる医療材料：ナノ絆創膏の開発 (2014)
  • Author(s): 藤枝 俊宣.
  • Organizer: 第8 回ナノ・バイオメディカル学会大会
  • Place of Presentation: 和歌山
  • Year and Date: 2014-05-02
  • Invited
• [Presentation] Injectable Micropatterned Polymeric Nanosheets for Local Delivery of an Engineered Epithelial Monolayer. (2014)
  • Author(s): Fujie, T., Mori, Y., Nishizawa, M., Nagai, N., Abe, T., Khademhosseini, A., Kaji, H.
  • Organizer: 2014 MRS Spring Meeting & Exhibit
  • Place of Presentation: San Francisco
  • Year and Date: 2014-04-21 – 2014-04-25
• [Presentation] 機能性高分子ナノシートからなる革新的組織工学材料の創製 (2014)
  • Author(s): 藤枝 俊宣
  • Organizer: 日本化学会第94春季年会(2014)
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] Flexible nanomembranes for directing cellular organization (2013)
  • Author(s): Fujie, T., Liu, H., Nakajima, K., Kaji, H., Khademhosseini, A.
  • Organizer: International Soft Matter Conference 2013 (ISMC 2013)
  • Place of Presentation: Rome
• [Presentation] Local Delivery of Engineered Cell Monolayer Directed by Micropatterned Polymeric Nanosheets (2013)
  • Author(s): 藤枝 俊宣
  • Organizer: 日本バイオマテリアル学会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 微細パターン化高分子ナノシートによる細胞移植療法の開発 (2013)
  • Author(s): 藤枝 俊宣, 森 好弘, 伊藤 俊太郎, 永井 展裕, 西澤 松彦, 阿部 俊明, Khademhosseini Ali, 梶 弘和
  • Organizer: 第62回高分子討論会
  • Place of Presentation: 金沢
• [Presentation] マイクロパターン化高分子ナノシートを用いた細胞デリバリー担体の開発 (2013)
  • Author(s): 藤枝 俊宣, 森 好弘, 伊藤 俊太郎, 西澤 松彦, 永井 展裕, 阿部 俊明, Khademhosseini Ali, 梶 弘和
  • Organizer: 医用高分子研究会
  • Place of Presentation: 東京
• [Book] 「高分子ナノシートの柔軟性と密着性を利用した「ナノ絆創膏」の開発と医療応用（第3章18節）」生体模倣技術と新材料･新製品開発への応用 (2014)
  • Author(s): 藤枝 俊宣, 木下 学.
  • Total Pages: 8
  • Publisher: 技術情報協会
• [Book] Development of Nanosheet Technology Towards Advanced Nanomedical Engineering (ch. 6), in Nanobiotechnology (2014)
  • Author(s): Fujie, T., Takeoka, S.
  • Total Pages: 27
  • Publisher: One Central Press
• [Book] Bioinspired Muscle Tissue Devices (ch. 35), in Handbook of Biomimetics and Bioinspiration (2014)
  • Author(s): Fujie, T., Ostrovidov, S., Ahadian, S., S. Prakash Parthiban, Khademhosseini, A., Kaji, H
  • Total Pages: 16
  • Publisher: World Scientific Publishing
• [Remarks] 早稲田大学 生体分子集合科学研究室
  • URL: http://www.takeoka.biomed.sci.waseda.ac.jp/
• [Remarks] 早稲田大学 アクティヴ・エイジング研究所
  • URL: http://www.kikou.waseda.ac.jp/jyuten/WSD322_open.php?KikoId=06&KenkyujoId=7J&kbn=0
• [Remarks] バイオマテリアル: 移植用細胞を低侵襲的に送り届けるナノカーペット
  • URL: http://research.wpi-aimr.tohoku.ac.jp/jpn/research/811
• [Remarks] バイオマテリアル: 細胞を整列させる
  • URL: https://research.wpi-aimr.tohoku.ac.jp/jpn/research/775
• [Remarks] バイオマテリアル: 移植用細胞を低侵襲的に送り届けるナノカーペット
  • URL: http://research.wpi-aimr.tohoku.ac.jp/jpn/research/811
• [Remarks] バイオマテリアル: 細胞を整列させる
  • URL: http://research.wpi-aimr.tohoku.ac.jp/jpn/research/775
• [Remarks] 早稲田大学 生体分子集合科学研究室
  • URL: http://www.takeoka.biomed.sci.waseda.ac.jp/index.php
• [Patent(Industrial Property Rights)] 形状制御されたナノシート及びその製造方法 (2015)
  • Inventor(s): 岩瀬英治,新保創太,武岡真司,藤枝俊宣,梶 弘和,阿部俊明
  • Industrial Property Rights Holder: 岩瀬英治,新保創太,武岡真司,藤枝俊宣,梶 弘和,阿部俊明
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-043990
  • Filing Date: 2015-03-05
• [Patent(Industrial Property Rights)] 細胞担持パターン化ナノ薄膜 (2013)
  • Inventor(s): 梶 弘和、藤枝俊宣、森 好弘、西澤松彦、阿部俊明、永井展裕
  • Industrial Property Rights Holder: 梶 弘和、藤枝俊宣、森 好弘、西澤松彦、阿部俊明、永井展裕
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-137253
  • Filing Date: 2013-06-28