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Development of a new pancreatic fistula prevention material via pancreatic fluid-responsive crosslinking

Research Project

Project/Area Number 17H03464
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biofunction/Bioprocess
Research InstitutionThe University of Tokyo

Principal Investigator

Ito Taichi  東京大学, 大学院医学系研究科(医学部), 准教授 (50447421)

Co-Investigator(Kenkyū-buntansha) 酒井 康行  東京大学, 大学院工学系研究科(工学部), 教授 (00235128)
長谷川 潔  東京大学, 医学部附属病院, 教授 (20292906)
浦野 泰照  東京大学, 大学院薬学系研究科(薬学部), 教授 (20292956)
太田 誠一  東京大学, 大学院医学系研究科(医学部), 助教 (40723284)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords医用化学工学 / バイオマテリアル / 膵臓がん / ハイドロゲル / 膵液
Outline of Final Research Achievements

We have developed a hydrogel using the Michael addition reaction of PEG-SH (thiolated polyethylene glycol) and PEG-AC (acrylated polyethylene glycol). It was confirmed that the 3-branched PEG-SH and 4-branched PEG-AC gels have a higher crosslink density. One of the important performances of pancreatic fistula-preventing material is to suppress leakage of enzymes such as trypsin and chymotrypsin, which are contained in pancreatic juice. In addition to the injectable gel, a PEG-SH / PEG-AC gel was lyophilized to produce a sponge with a dense gel network, which blocked permeation of the pancreatic secretory trypsin. We administrated the hydrogel into a rat common duct transection model, the volume of ascites in the gel group tended to decrease compared to that in the control group.

Academic Significance and Societal Importance of the Research Achievements

年々増え続ける膵臓がんの患者数は,日本で年間4万人弱,そのうち手術適用は30%程度と言われている.さらに海外での膵がん死亡者数は年間33万人と推計されている.外科的切除の適用拡大が望まれるが,現状では約1ヵ月に渡る術後管理が困難で,手術のリスクを押し上げている.この原因が,膵液瘻である.消化酵素を含む膵液が膵臓切除部の縫合部より,膵液が消化器の外の空間である腹腔に漏出すると,周囲の組織や血管を溶解し,重篤なケースは死に至る.膵臓切除術を安全に行うためには,膵液瘻防止材料が必要不可欠である.本研究では,膵液瘻防止材料の開発と,ドラッグデリバリーシステムに関する基礎的知見を得た.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (47 results)

All 2020 2019 2018 2017 Other

All Journal Article (12 results) (of which Peer Reviewed: 10 results) Presentation (25 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results) Book (7 results) Remarks (3 results)

  • [Journal Article] Prevention of postoperative peritoneal adhesions in rats with sidewall defect-bowel abrasions using metal ion-crosslinked N-succinyl chitosan hydrogels2019

    • Author(s)
      Mitsuhashi Kento、Qi Pan、Takahashi Akira、Ohta Seiichi、Ito Taichi
    • Journal Title

      Reactive and Functional Polymers

      Volume: 145 Pages: 104374-104374

    • DOI

      10.1016/j.reactfunctpolym.2019.104374

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Prevention of Hepatectomy-Induced Adhesions by Bilayer Sponge Composed of Ultrapure Alginate2019

    • Author(s)
      Ohta Seiichi、Toda Takeo、Inagaki Fuyuki、Omichi Kiyohiko、Shimizu Atsushi、Kokudo Norihiro、Hasegawa Kiyoshi、Ito Taichi
    • Journal Title

      Journal of Surgical Research

      Volume: 242 Pages: 286-295

    • DOI

      10.1016/j.jss.2019.04.063

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Facile fabrication of PEG-coated PLGA microspheres via SPG membrane emulsification for the treatment of scleroderma by ECM degrading enzymes2019

    • Author(s)
      Ohta Seiichi、Matsuura Mai、Kawashima Yuta、Cai Xinyu、Taniguchi Machiko、Okochi Hitoshi、Asano Yoshihide、Sato Shinichi、Ito Taichi
    • Journal Title

      Colloids and Surfaces B: Biointerfaces

      Volume: 179 Pages: 453-461

    • DOI

      10.1016/j.colsurfb.2019.04.028

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pemetrexed-conjugated hyaluronan for the treatment of malignant pleural mesothelioma2019

    • Author(s)
      Amano Yuki、Ohta Seiichi、Sakura Kazuma L.、Ito Taichi
    • Journal Title

      European Journal of Pharmaceutical Sciences

      Volume: 138 Pages: 105008-105008

    • DOI

      10.1016/j.ejps.2019.105008

    • Related Report
      2019 Annual Research Report
  • [Journal Article] An Injectable Hemostat Composed of a Polyphosphate-Conjugated Hyaluronan Hydrogel2018

    • Author(s)
      Megumu Sakoda, Makoto Kaneko, Seiichi Ohta, Pan Qi, Shigetoshi Ichimura, Yutaka Yatomi, and Taichi Ito
    • Journal Title

      Biomacromolecules

      Volume: 19(8) Issue: 8 Pages: 3280-3290

    • DOI

      10.1021/acs.biomac.8b00588

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fabrication of calcium phosphate-loaded carboxymethyl cellulose non-woven sheets for bone regeneration.2018

    • Author(s)
      Qi P, Ohba S, Hara Y, Fuke M, Ogawa T, Ohta S, Ito T
    • Journal Title

      Carbohydr Polym

      Volume: 189 Pages: 322-330

    • DOI

      10.1016/j.carbpol.2018.02.050

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevention of peritoneal adhesions by ferric ion-crosslinked hydrogels of hyaluronic acid modified with iminodiacetic acid2018

    • Author(s)
      Yuki Amano, Pan Qi, Yoshiyuki Nakagawa, Katsuhisa Kirita, Seiichi Ohta, and Taichi Ito
    • Journal Title

      ACS Biomaterials Science and Engineering

      Volume: 4(9) Issue: 9 Pages: 3405-3412

    • DOI

      10.1021/acsbiomaterials.8b00456

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ion-responsive fluorescence resonance energy transfer between grafted polyacrylic acid arms of star block copolymers2018

    • Author(s)
      Y. Amano, Y. Nakagawa, S. Ohta and T. Ito
    • Journal Title

      Polymer

      Volume: 137 Pages: 169-172

    • DOI

      10.1016/j.polymer.2018.01.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intraperitoneal delivery of cisplatin via a hyaluronan-based nanogel/in situ crosslinkable hydrogel hybrid system for peritoneal dissemination of gastric cancer2017

    • Author(s)
      Seiichi Ohta,Shota Hiramoto, Yuki Amano, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Joji Kitayama, and Taichi Ito
    • Journal Title

      Molecular Pharmaceutics

      Volume: 14 Issue: 9 Pages: 3105-3113

    • DOI

      10.1021/acs.molpharmaceut.7b00349

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In Vivo Redox-Responsive Sol-Gel/Gel-Sol Transition of Star Block Copolymer Solution Based on Ionic Cross-Linking2017

    • Author(s)
      Yoshiyuki Nakagawa, Seiichi Ohta, Akira Sugahara, Masashi Okubo, Atsuo Yamada, and Taichi Ito
    • Journal Title

      Macromolecules

      Volume: 50 Issue: 14 Pages: 5539-5548

    • DOI

      10.1021/acs.macromol.7b01020

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictors of Postoperative Non-Chylous Massive Discharge after Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma.2017

    • Author(s)
      Ito K, Kawaguchi Y, Sakamoto Y, Arita J, Hasegawa K, Kokudo N.
    • Journal Title

      Digestive Surgery

      Volume: 35 Issue: 3 Pages: 1-9

    • DOI

      10.1159/000479341

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 薬物徐放ゲルのニーズー要求特性と応用例2017

    • Author(s)
      伊藤 大知
    • Journal Title

      MATERIALSTAGE

      Volume: 17 Pages: 40-44

    • Related Report
      2017 Annual Research Report
  • [Presentation] Pressure drop during endoscopic delivery of clay-based hydrogel2020

    • Author(s)
      Athira Sreedevi Madhavikutty・Seiichi Ohta・Pan Qi・Taichi Ito
    • Organizer
      化学工学会 第85年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 内視鏡的粘膜下層剥離術後の食道狭窄防止するためのin situ架橋パウダー材料の開発2020

    • Author(s)
      戚蟠・ 太田誠一・藤澤彩乃・辻陽介・藤城光弘・伊藤大知
    • Organizer
      第19回日本再生医療学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 拡散防止効果を持った生分解性高架橋密度ポリエチレングリコールスポンジの開発2019

    • Author(s)
      三橋健斗・太田誠一・伊藤大知
    • Organizer
      膜シンポジウム2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 金属イオン架橋コハク酸修飾キトサンハイドロゲルによる術後腹膜癒着防止効果の検討2019

    • Author(s)
      三橋健斗・戚蟠・高橋彬・太田誠一・伊藤大知
    • Organizer
      第41回日本バイオマテリアル学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癒着防止材の開発と応用展開2019

    • Author(s)
      伊藤大知
    • Organizer
      第46回日本血液浄化技術学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Spray application of in situ cross-linkable powders for preventing esophageal stenosis after endoscopic submucosal dissection2019

    • Author(s)
      Pan Qi・Seiichi OHTA・Ayano FUJISAWA・Yosuke TSUJI・Mitsuhiro FUJISHIRO・Taichi ITO
    • Organizer
      Asian Pacific Confederation of Chemical Engineering 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gelation behavior of shear-thinning hydrogels fabricated via a Kenics static mixer2019

    • Author(s)
      Athira Sreedevi Madhavikutty・Seiichi Ohta・Taichi Ito
    • Organizer
      Asian Pacific Confederation of Chemical Engineering 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of PEG coated PLGA microspheres encapsulating ECM degrading enzymes via SPG membrane emulsification for the treatment of scleroderma2019

    • Author(s)
      Xinyu Cai・Mai Matsuura・Yuta Kawashima・Seiichi Ohta・Machiko Taniguchi ・Hitoshi Okochi・Yoshihide Asano・Shinichi Sato・Taichi Ito
    • Organizer
      膜シンポジウム2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] In situ cross-linkable powder spray application for preventing esophageal stenosis after endoscopic submucosal dissection2019

    • Author(s)
      Pan Qi・Seiichi OHTA・Ayano FUJISAWA・Yosuke TSUJI・Mitsuhiro FUJISHIRO・Taichi ITO
    • Organizer
      NCRM NICHE 2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] イミノ二酢酸修飾ヒアルロン酸鉄イオン架橋ハイドロゲルによる腹膜癒着防止効果の検討2019

    • Author(s)
      天野由貴・戚蟠・中川慶之・切田勝久・太田誠一・伊藤大知
    • Organizer
      東京大学医学部附属病院先端医療シーズフォーラム2019
    • Related Report
      2018 Annual Research Report
  • [Presentation] バイオマテリアルを用いた再生医療 ーinjectableゲル材料・シート材料の応用ー2019

    • Author(s)
      伊藤大知
    • Organizer
      日本医工学治療学会第35回学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] エレクトロスプレー法による細胞封入アルギン酸カプセルのモルフォロジー制御と細胞機能評価2019

    • Author(s)
      大木悠一朗・太田誠一・上平正道・伊藤大知
    • Organizer
      化学工学会 第84年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Dynamic Control of ECM by In Situ Conjugation of Bioactive Peptides in Capsule Culture2019

    • Author(s)
      大木悠一朗・太田誠一・大庭伸介・伊藤大知
    • Organizer
      第84年会 日中化工シンポジウム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development and application of in situ crosslinking poly ethylene glycol hydrogel for prevention of pancreatic fistula2018

    • Author(s)
      Kento Mitsuhashi, Rihito Nagata, Seiichi Ohta, Junichi Arita, Kiyoshi Hasegawa, Taichi Ito
    • Organizer
      Biomaterials International 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bone regeneration facilitated by calcium phosphate-loaded carboxymethyl cellulose non-woven sheets2018

    • Author(s)
      Pan Qi, Shinsuke Ohba, Yuichi Hara, Masaya Fuke, Takayuki Ogawa, Seiichi Ohta, Taichi Ito
    • Organizer
      Biomaterials International 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ポリロタキサン/ゼラチンからなる伸縮性を有した新規in situ架橋ハイドロゲルの開発2018

    • Author(s)
      中野剛志・太田誠一・伊藤大知
    • Organizer
      化学工学会室蘭大会 2018(3支部合同大会)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 3D Inkjet Printing of Ionically Cross-linked Star Block Copolymer Hydrogels2018

    • Author(s)
      Taichi Ito,Yoshiyuki Nakagawa,Seiichi Ohta,Makoto Nakamura
    • Organizer
      5th TERMIS World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Osteogenic differentiation induced by in situ conjugation of BMP-2 mimetic peptide to microcapsule2018

    • Author(s)
      Yuichiro Oki, Seiichi Ohta, Shinsuke Ohba, and Taichi Ito
    • Organizer
      NCRM-NICHE, Shibaura Institute of Technology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マイクロカプセル培養下での生理活性ペプチドのin situ conjugation2018

    • Author(s)
      大木悠一朗・太田誠一・大庭伸介・伊藤大知
    • Organizer
      40回日本バイオマテリアル学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 膵液瘻防止を目指したポリエチレングリコールin situ 架橋ゲルの開発2018

    • Author(s)
      三橋健斗・長田梨比人・太田誠一・有田淳一・長谷川潔・伊藤大知
    • Organizer
      化学工学会 第83年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Intraperitoneal delivery of cisplatin via hyaluronan-based nanogel/in situ cross-linkable hydrogel hybrid system for peritoneal dissemination of gastric cancer2017

    • Author(s)
      Shota Hiramoto, Seiichi Ohta, Yuki Amano, Shigenobu Emoto, Hironori Yamaguchi, Hironori Ishigami, Joji Kitayama, Taichi Ito
    • Organizer
      The 14th US-Japan symposium on drug delivery systems
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腹膜播種治療のためのヒアルロン酸ナノゲル/in situ架橋ゲルハイブリッドの開発2017

    • Author(s)
      太田誠一・平本翔大・天野由貴・江本成伸・山口博紀・石神浩徳・北山丈二・伊藤大知
    • Organizer
      化学工学会 第49回秋季大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酸化還元応答性鉄イオン架橋スターブロックコポリマーゲルの開発2017

    • Author(s)
      中川慶之・太田誠一・伊藤大知
    • Organizer
      化学工学会東京大会2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗線溶薬封入ヒアルロン酸ゲルのプラスミン阻害による抗線溶効果の検討2017

    • Author(s)
      迫田龍・太田誠一・伊藤大知
    • Organizer
      化学工学会東京大会2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Postoperative complication after pancreatoduodenectomy with artery-first approach2017

    • Author(s)
      Arita J, Sakamoto Y, Akamatsu N, Kaneko J, Hasegawa K, Kokudo N
    • Organizer
      第25回日本消化器関連学会週間(JDDW 2017)
    • Related Report
      2017 Annual Research Report
  • [Book] 次世代のポリマー・高分子開発,新しい用途展開と将来展望-生分解,自己修復,生物模倣,刺激応答,超分子,医療用途など- 第7章 第1節 スターブロックコポリマーを用いたinjectable医用ハイドロゲル材料の開発2019

    • Author(s)
      伊藤大知
    • Total Pages
      5
    • Publisher
      技術情報協会
    • ISBN
      9784861047381
    • Related Report
      2019 Annual Research Report
  • [Book] 再生医療の開発戦略と最新研究事例集 第3章 「再生医療用足場材料に期待される素材の研究と製品化 第4節 ハイドロゲルの再生医療用足場材料への応用2019

    • Author(s)
      戚 蟠、伊藤大知
    • Total Pages
      5
    • Publisher
      (株)エヌ・ティー・エス
    • Related Report
      2019 Annual Research Report
  • [Book] 次世代のポリマー・高分子開発,新しい用途展開と将来展望 -生分解,自己修復,生物模倣,刺激応答,超分子,医療用途など- 第7章 「医療用高分子・ポリマーの設計,その応用と可能性 第1節 スターブロックコポリマーを用いたinjectable医用ハイドロゲル材料の開発」2019

    • Author(s)
      伊藤大知
    • Total Pages
      608
    • Publisher
      技術情報協会
    • Related Report
      2018 Annual Research Report
  • [Book] 再生医療の開発戦略と最新研究事例集  第3章 「再生医療用足場材料に期待される素材の研究と製品化 第4節 ハイドロゲルの再生医療用足場材料への応用」2019

    • Author(s)
      伊藤大知
    • Total Pages
      420
    • Publisher
      技術情報協会
    • Related Report
      2018 Annual Research Report
  • [Book] 刺激応答性高分子ハンドブック 第6章 その他の応答 第3節 癒着防止用インジェクタブルゲル2018

    • Author(s)
      伊藤大知
    • Total Pages
      864
    • Publisher
      (株)エヌ・ティー・エス
    • Related Report
      2018 Annual Research Report
  • [Book] Biomedical Engineering Challenges: A Chemical Engineering Insight2018

    • Author(s)
      Vincenzo Piemonte (Editor), Angelo Basile (Editor), Taichi Ito (Editor), Luigi Marrelli (Editor)
    • Total Pages
      256
    • Publisher
      Wiely
    • ISBN
      9781119296041
    • Related Report
      2017 Annual Research Report
  • [Book] 生体吸収性材料の開発と安全性評価 内視鏡手術に有望な吸収性止血材の材料とその評価2017

    • Author(s)
      伊藤大知
    • Total Pages
      465
    • Publisher
      技術情報協会
    • ISBN
      9784861046896
    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京大学 大学院医学系研究科 疾患生命工学センター 医療材料・機器工学部門 伊藤研究室HP

    • URL

      http://www.cdbim.m.u-tokyo.ac.jp/itolab/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 伊藤研究室ホームぺ―ジ

    • URL

      http://www.cdbim.m.u-tokyo.ac.jp/itolab/publications.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京大学大学院医学系研究科疾患生命工学センター医療材料・機器工学部門

    • URL

      http://www.cdbim.m.u-tokyo.ac.jp/itolab/index.html

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-03-11  

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