Establishment of rheological control method of transient network by topology control and development of novel ophthalmic viscosurgical device

• Project/Area Number: 20K15338
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 35020:Polymer materials-related
• Research Institution: The University of Tokyo
• Principal Investigator: Katashima Takuya 東京大学, 大学院工学系研究科(工学部), 講師 (20759188)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: レオロジー / 一時網目 / 粘弾性 / 動的共有結合 / 白内障

Outline of Research at the Start

本申請では、網目トポロジーとレオロジー特性の相関を調べ、一時網目のレオロジー特性の学理を解明し、得られた指導原理に基づき、新規眼内手術補助剤のプロトタイプを開発する。
材料のレオロジー制御は、医療現場で重要であったが、従来の材料ではニーズに合う物性を理論上到達しえず、根本的な改善が必要であった。近年、会合点に寿命のある一時網目が注目されているが、レオロジー特性を精密制御できる材料や理論もない状態である。
申請者は最近、一時網目のトポロジーを変えることで、レオロジー特性を制御できる可能性を発見した。そこでトポロジーの異なる一時網目を作り分け、その学理を解明し、新規レオロジー制御材の開発をする。

Outline of Final Research Achievements

In this study, I aimed to investigate the correlation between network topology and rheological properties, clarify the principles of transient networks, and develop a prototype for a new ophthalmic surgical adjuvant based on the obtained guiding principles. Controlling the rheology of materials has been crucial in the medical field, but conventional materials have not been able to satisfy the required properties, necessitating fundamental improvements. The applicant systematically investigated the relationship between linear and non-linear viscoelastic characteristics and network structures by altering the topology, and clarified the mechanisms. Furthermore, based on the acquired scientific principles, we have established a technology that allows for the coexistence of storage and injectability, which had previously been in a trade-off relationship, by utilizing flow-induced phase separation. Based on these results, we developed a prototype for an ophthalmic adjuvant.

Academic Significance and Societal Importance of the Research Achievements

過渡的網目材料のレオロジー特性は、会合点のミクロな会合・脱離のダイナミクスからマクロな粘弾性までマルチスケールの制御・解析が必要であった。本申請では、構造の制御されたモデル材料を用いることで、種々のスケールのダイナミクスを系統的に評価し、比較することで新しい学理を構築した。
得られた学理は、今後、過渡的網目材料を実在料として応用する際の、設計指針の根幹をなすものであり、レオロジーの学問領域を大幅に広げるものである。

Research Products

• [Journal Article] Molecular Weight-dependent Diffusion, Biodistribution, and Clearance Behavior of Tetra-armed Poly(ethylene glycol) Subcutaneously Injected into the Back of Mice. (2023)
  • Author(s): Ishikawa S, Kato M, Si J, Yu L, Kimura K, Katashima T, Naito M, Kurita M, Sakai T.
  • Journal Title: ACS Macro Letter Volume: 12 Issue: 4 Pages: 510-517
  • DOI: 10.1021/acsmacrolett.3c00044
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Understanding of Viscoelasticity in Transient Polymer Networks Based on Multiple Methods (2022)
  • Author(s): Katashima Takuya
  • Journal Title: Nihon Reoroji Gakkaishi Volume: 50 Issue: 1 Pages: 51-56
  • DOI: 10.1678/rheology.50.51
  • ISSN: 0387-1533, 2186-4586
  • Year and Date: 2022-02-15
  • Peer Reviewed
• [Journal Article] Non-swellability of polyelectrolyte gel in divalent salt solution due to aggregation formation (2022)
  • Author(s): Jian Tang, Takuya Katashima, Caidric Indaya Gupit, Xiang Li, Yoshiro Mitsukami, Yuki Yokoyama, Naoyuki Sakumichi, Ung-il Chung, Mitsuhiro Shibayama, Takamasa Sakai
  • Journal Title: Polymer Volume: 250 Pages: 124894-124894
  • DOI: 10.1016/j.polymer.2022.124894
  • Peer Reviewed
• [Journal Article] Experimental Comparison of Bond Lifetime and Viscoelastic Relaxation in Transient Networks with Well-Controlled Structures (2022)
  • Author(s): Katashima Takuya、Kudo Ryota、Naito Mitsuru、Nagatoishi Satoru、Miyata Kanjiro、Chung Ung-il、Tsumoto Kouhei、Sakai Takamasa
  • Journal Title: ACS Macro Letters Volume: 11 Issue: 6 Pages: 753-759
  • DOI: 10.1021/acsmacrolett.2c00152
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of the sustained release ability of bevacizumab-loaded tetra-PEG gel (2022)
  • Author(s): Murakami Tomoya、Hoshi Sujin、Okamoto Fumiki、Sakai Takamasa、Katashima Takuya、Naito Mitsuru、Oshika Tetsuro
  • Journal Title: Experimental Eye Research Volume: 223 Pages: 109206-109206
  • DOI: 10.1016/j.exer.2022.109206
  • Peer Reviewed / Open Access
• [Journal Article] Effects of network connectivity on viscoelastic relaxation in transient networks using experimental approach (2022)
  • Author(s): Katashima Takuya、Kudo Ryota、Onishi Ryoya、Naito Mitsuru、Nagatoishi Satoru、Miyata Kanjiro、Tsumoto Kouhei、Chung Ung-Il、Sakai Takamasa
  • Journal Title: Frontiers in Soft Matter Volume: 2 Pages: 1059156-1059156
  • DOI: 10.3389/frsfm.2022.1059156
  • Peer Reviewed / Open Access
• [Journal Article] Decoupling between Translational Diffusion and Viscoelasticity in Transient Networks with Controlled Network Connectivity (2022)
  • Author(s): Katashima Takuya、Kobayashi Ryunosuke、Ishikawa Shohei、Naito Mitsuru、Miyata Kanjiro、Chung Ung-il、Sakai Takamasa
  • Journal Title: Gels Volume: 8 Issue: 12 Pages: 830-830
  • DOI: 10.3390/gels8120830
  • Peer Reviewed / Open Access
• [Journal Article] Star-Polymer-DNA Gels Showing Highly Predictable and Tunable Mechanical Responses (2022)
  • Author(s): Ohira Masashi、Katashima Takuya、Naito Mitsuru、Aoki Daisuke、Yoshikawa Yusuke、Iwase Hiroki、Takata Shin‐ichi、Miyata Kanjiro、Chung Ung‐il、Sakai Takamasa、Shibayama Mitsuhiro、Li Xiang
  • Journal Title: Advanced Materials Volume: 34 Issue: 13 Pages: 2108818-2108818
  • DOI: 10.1002/adma.202108818
  • Peer Reviewed
• [Journal Article] Rheological studies on polymer networks with static and dynamic crosslinks (2021)
  • Author(s): Katashima Takuya
  • Journal Title: Polymer Journal Volume: 53 Issue: 10 Pages: 1073-1082
  • DOI: 10.1038/s41428-021-00505-y
  • Peer Reviewed
• [Journal Article] Temperature Dependence of Polymer Network Diffusion (2021)
  • Author(s): Takeshi Fujiyabu, Takamasa Sakai, Ryota Kudo, Yuki Yoshikawa, Takuya Katashima, Ung-il Chung, Naoyuki Sakumichi
  • Journal Title: Physical Review Letters Volume: 127 Issue: 23 Pages: 237801-237801
  • DOI: 10.1103/physrevlett.127.237801
  • Peer Reviewed
• [Journal Article] Effect of Nonlinear Elasticity on the Swelling Behaviors of Highly Swollen Polyelectrolyte Gels (2021)
  • Author(s): Tang Jian、Katashima Takuya、Li Xiang、Mitsukami Yoshiro、Yokoyama Yuki、Chung Ung-il、Shibayama Mitsuhiro、Sakai Takamasa
  • Journal Title: Gels Volume: 7 Issue: 1 Pages: 25-25
  • DOI: 10.3390/gels7010025
  • Peer Reviewed / Open Access
• [Journal Article] Similarity in Linear Viscoelastic Behaviors of Network Formation and Degradation Processes (2020)
  • Author(s): Katashima Takuya、Kagami Ryo、Chung Ung-il、Sakai Takamasa
  • Journal Title: Nihon Reoroji Gakkaishi Volume: 48 Issue: 4 Pages: 191-198
  • DOI: 10.1678/rheology.48.191
  • NAID: 130007926358
  • ISSN: 0387-1533, 2186-4586
  • Year and Date: 2020-09-15
  • Peer Reviewed
• [Journal Article] Mixing and Elastic Contributions to the Diffusion Coefficient of Polymer Networks (2020)
  • Author(s): Junhyuk Kim, Takeshi Fujiyabu, Naoyuki Sakumichi, Takuya Katashima, Yuki Yoshikawa, Ung-il Chung, and Takamasa Sakai
  • Journal Title: Macromolecules Volume: 53 Issue: 18 Pages: 7717-7725
  • DOI: 10.1021/acs.macromol.0c01427
  • Peer Reviewed
• [Journal Article] Swelling Behaviors of Hydrogels with Alternating Neutral/Highly Charged Sequences (2020)
  • Author(s): Jian Tang, Takuya Katashima, Xiang Li, Yoshiro Mitsukami, Yuki Yokoyama, Naoyuki Sakumichi, Ung-il Chung, Mitsuhiro Shibayama, and Takamasa Sakai
  • Journal Title: Macromolecules Volume: 53 Issue: 19 Pages: 8244-8254
  • DOI: 10.1021/acs.macromol.0c01221
  • Peer Reviewed
• [Presentation] Molecular Origin of Viscoelasticity in Dynamic-crosslinked Gels with Well-Controlled Structures (2022)
  • Author(s): Takuya Katashima, Ryota Kudo, Mitsuru Naito, Satoru Nagatoishi, Kanjiro Miyata, Ung-il Chung, Kohei Tsumoto, Takamasa Sakai
  • Organizer: 13th International Gel Symposium
  • Int'l Joint Research
• [Presentation] Mechanical Properties of Dynamic Cross-Linked Hydrogels with well-controlled structures and Biomedical Applications (2022)
  • Author(s): Takuya Katashima
  • Organizer: 第71回高分子討論会日韓ジョイントセッション
  • Invited
• [Presentation] 網目構造の制御された会合性高分子網目を用いたミクロ動力学とマクロ物性の相関解明 (2022)
  • Author(s): 片島拓弥
  • Organizer: 第98回高分子若手研究会[関西]
  • Invited
• [Presentation] 星型ポリマーからなる会合性網目の物性とバイオマテリアル応用への試み (2022)
  • Author(s): 片島拓弥
  • Organizer: 第183回東海高分子研究会講演会（夏季研究会）
  • Invited
• [Presentation] Overshoot behavior of dynamically crosslinked hydrogels under start-up shear flow (2022)
  • Author(s): Ryoya Onishi, Takuya Katashima, Mitsuru Naito, Kanjiro Miyata, Ung-il Chung, Takamasa Sakai
  • Organizer: 第71回高分子討論会
• [Presentation] 構造明確な過渡的高分子網目の定常流動下におけるオーバーシュート挙動 (2022)
  • Author(s): 大西遼哉、片島拓弥、内藤瑞、宮田完二郎、鄭雄一、酒井崇匡
  • Organizer: 第70回レオロジー討論会
• [Presentation] Semidilute scaling law of osmotic pressure for polymer gel swelling (2022)
  • Author(s): Takashi Yasuda, Naoyuki Sakkumichi, and Takamasa Sakai
  • Organizer: Polymer Network Group 2022
  • Int'l Joint Research
• [Presentation] Universal equation of state of osmotic pressure in polymer network system (2022)
  • Author(s): Takashi Yasuda, Naoyuki Sakkumichi, and Takamasa Sakai
  • Organizer: Canadian Material Science Conference 2022
  • Int'l Joint Research
• [Presentation] Semidilute scaling principle for polymer gels (2022)
  • Author(s): Takashi Yasuda, Naoyuki Sakkumichi, and Takamasa Sakai
  • Organizer: Gel Sympo 2022
  • Int'l Joint Research
• [Presentation] Universality of osmotic pressure in dynamic covalent networks (2022)
  • Author(s): Takashi Yasuda, Takuya Katashima, Naoyuki Sakumichi, Mitsuru Naito, Kanjiro Miyata, Ung-il Chung, and Takamasa Sakai
  • Organizer: 第71回高分子討論会
• [Presentation] 過渡的網目の粘弾性緩和と網目構造の相関 (2022)
  • Author(s): 片島拓弥、工藤凌太、内藤 瑞、宮田完二郎、鄭雄一、酒井崇匡、長門石暁、津本浩平
  • Organizer: 第70回レオロジー討論会
• [Presentation] 末端会合性網目の異常拡散と会合ダイナミクスの関係 (2022)
  • Author(s): 小林隆之助, 片島拓弥, 石川昇平, 工藤俊太, 内藤瑞, 津本浩平, 長門石暁, 鄭雄一, 酒井崇匡
  • Organizer: 関東高分子若手研究会 2022年度 学生発表会・交流会
• [Presentation] 4分岐高分子からなる一時網目の粘弾性とその分子機構 (2021)
  • Author(s): 工藤稜太、片島拓弥、内藤瑞、宮田完二郎、鄭雄一、酒井崇匡
  • Organizer: レオロジー学会 第48年会
• [Presentation] 均一な分岐構造を持つスライムのミクロな会合挙動とマクロな粘弾性の相関 (2021)
  • Author(s): 工藤稜太、片島拓弥、内藤瑞、長門石曉、宮田完二郎、鄭雄一、津本浩平、酒井崇匡
  • Organizer: 第70回高分子討論会
• [Presentation] 過渡的網目の会合動力学と粘弾性緩和の相関 (2021)
  • Author(s): 工藤稜太、片島拓弥、内藤瑞、宮田完二郎、津本浩平、長門石曉、鄭 雄一、酒井崇匡
  • Organizer: 第69回レオロジー討論会
• [Presentation] Mechanical Properties of Doubly Crosslinked Gels (2021)
  • Author(s): 片島拓弥
  • Organizer: 第70回高分子学会年次大会
  • Invited
• [Presentation] スライムのレオロジー (2021)
  • Author(s): 片島拓弥
  • Organizer: 関東高分子若手研究会 サマーキャンプ2021
  • Invited
• [Presentation] スライムの粘弾性緩和の分子機構 (2021)
  • Author(s): 片島拓弥
  • Organizer: 2021年度高分子化学構造・物性相関研究会
  • Invited
• [Presentation] Effect of nano-dissociation kinetics on macroscopic viscoelasticity in four-branched transient networks (2021)
  • Author(s): Takuya Katashima, Mitsuru Naito, Satoru Nagatoishi, Kanjiro Miyata, Ung-il Chung, Kohei Tsumoto, Takamaisa Sakai
  • Organizer: Material Research Meeting 2021
  • Int'l Joint Research
• [Presentation] Relationship between dissociation kinetics and viscoelasticity in four-branched transient networks (2021)
  • Author(s): 片島拓弥
  • Organizer: レオロジー講演会
• [Presentation] Viscoelastic Study on Transient Networks Composed of Mutually Reactive Branched Polymers (2020)
  • Author(s): Takuya Katashima
  • Organizer: 3rd GLowing Polymer Symposium in KANTO (GPS-K 2020)
  • Int'l Joint Research / Invited
• [Presentation] Mechanical properties of doubly crosslinked gels (2020)
  • Author(s): 片島拓弥
  • Organizer: 第69回高分子学会年次大会 (コロナウイルス蔓延のため中止であったが、発表としては成立)
  • Invited
• [Presentation] Viscoelasticity of Transient Networks Composed of Mutually Reactive Branched Polymer (2020)
  • Author(s): Takuya KATASHIMA, Mitsuru NAITO, Ung-il CHUNG, Kanjiro MIYATA, Takamasa SAKAI
  • Organizer: International Congress on Rheology (Online (Brazil))
  • Int'l Joint Research
• [Book] 動的粘弾性測定とそのデータ解釈事例 (2021)
  • Author(s): 執筆者：57名、技術情報協会
  • Total Pages: 589
  • Publisher: 技術情報協会
  • ISBN: 9784861048661
• [Remarks] 片島・鄭研究室ホームページ
  • URL: https://rheo.tokyo/
• [Remarks] 東京大学大学院工学系研究科バイオエンジニアリング専攻 酒井・鄭研究室ホームページ
  • URL: https://gel.tokyo/tetra-gel/
• [Remarks] 東京大学大学院工学系研究科バイオエンジニアリング専攻 酒井・鄭研究室ホームページ
  • URL: https://gel.tokyo/tetra-gel/
• [Patent(Industrial Property Rights)] 相分離構造を有する高分子材料 (2022)
  • Inventor(s): 片島拓弥、酒井崇匡、宮田完二郎、内藤瑞、増井公祐
  • Industrial Property Rights Holder: 片島拓弥、酒井崇匡、宮田完二郎、内藤瑞、増井公祐
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2022-076350
  • Filing Date: 2022
• [Patent(Industrial Property Rights)] 分岐数制御による相分離構造を有する高分子材料 (2022)
  • Inventor(s): 片島拓弥、酒井崇匡、宮田完二郎、内藤瑞、増井公祐
  • Industrial Property Rights Holder: 片島拓弥、酒井崇匡、宮田完二郎、内藤瑞、増井公祐
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2022-076349
  • Filing Date: 2022
• [Patent(Industrial Property Rights)] 粒子状物質を局所放出するためのキャリア材料 (2022)
  • Inventor(s): 片島拓弥、酒井崇匡、栗田昌和、石川昇平、鎌田宏幸、増井公祐
  • Industrial Property Rights Holder: 片島拓弥、酒井崇匡、栗田昌和、石川昇平、鎌田宏幸、増井公祐
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2022-169353
  • Filing Date: 2022
• [Patent(Industrial Property Rights)] 会合性高分子材料 (2020)
  • Inventor(s): 酒井崇匡、宮田完二郎、内藤瑞、片島拓弥、増井公祐
  • Industrial Property Rights Holder: 酒井崇匡、宮田完二郎、内藤瑞、片島拓弥、増井公祐
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-181612
  • Filing Date: 2020