The development of bioresorbable arterial graft that promote the vascular remodeling by macrophage infiltration from the outside of the graft

• Project/Area Number: 19K09279
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Nippon Medical School
• Principal Investigator: Miyachi Hideki 日本医科大学, 医学部, 助教 (90386235)
• Co-Investigator(Kenkyū-buntansha): 中澤 靖元 東京農工大学, 工学(系)研究科(研究院), 教授 (20456255) ; 大石 由美子 日本医科大学, 大学院医学研究科, 大学院教授 (80435734)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 生体吸収性動脈グラフト / 血管リモデリング / 細胞浸潤性試験 / 血管再生 / 生体吸収材料 / 動脈グラフト / 吸収性動脈グラフト / マクロファージ

Outline of Research at the Start

申請者らは、血管再生を促すスポンジ構造の内層と耐圧性を維持する機密性の高い外層から成る二層構造の生体吸収性血管グラフトを開発、マウス腹部大動脈への移植し良好なグラフト開存を得た。しかしこの気密性の高い外層は、外側からの細胞浸潤とそれに続く血管再生を
阻害していた。そこで本研究ではポアサイズや吸収期間が異なる外層を持った複数の動脈グラフトをラット腹部大動脈へ移植し、細胞浸潤性と血管再生の関係を評価する。
特に以下の2課題について検討する。
課題１；吸収期間やポアサイズの異なる外層を持った二層性動脈グラフトの作製
課題２；作成したグラフトを用いた再生血管の評価

Outline of Final Research Achievements

In bioresorbable arterial graft, the vascular structure needs to be regenerated before the bioresorbable material is absorbed completely. We developed a bilayer graft with a sponge inner layer to promote cell infiltration and an electrospun outer layer to endure arterial pressure. In vitro studies revealed that sheets with pore sizes of 2um and 10um showed inadequate cell infiltration, while sheets with 20um were technically difficult to fabricate. The ideal bilayered graft was difficult to create using this method. In the future, grafts with a hierarchical structure with different absorption periods will be prepared.

Academic Significance and Societal Importance of the Research Achievements

理想的な生体吸収性動脈グラフトはいまだ開発途上であり、二層性グラフトはグラフト外側からの細胞浸潤に着目した点で血管再生を促進する可能性が考えられた。しかし理想的な細胞浸潤と耐圧性を得るための二層性グラフトは技術的に困難であった。このことから今後は階層構造を持ったグラフトの作成を行っていくこととした。今回の実験からより理想的なグラフト作製への道筋が一つ開けた可能性がある。

Research Products

• [Journal Article] Improvement of a Novel Small-diameter Tissue-engineered Arterial Graft With Heparin Conjugation (2021)
  • Author(s): Matsuzaki Yuichi、Miyamoto Shinka、Miyachi Hideki、Iwaki Ryuma、Shoji Toshihiro、Blum Kevin、Chang Yu-Chun、Kelly John、Reinhardt James W.、Nakayama Hidetaka、Breuer Christopher K.、Shinoka Toshiharu
  • Journal Title: The Annals of Thoracic Surgery Volume: 111 Issue: 4 Pages: 1234-1241
  • DOI: 10.1016/j.athoracsur.2020.06.112
  • Peer Reviewed / Open Access
• [Journal Article] A novel gradient and multilayered sheet with a silk fibroin/polyvinyl alcohol core?shell structure for bioabsorbable arterial grafts (2021)
  • Author(s): Koyanagi Eri、Tara Shuhei、Sakata Chiemi、Shimada Kazumi、Kato Konosuke、Miyachi Hideki、Tanaka Ryou、Nakazawa Yasumoto
  • Journal Title: Journal of Biomedical Materials Research Part A Volume: 110 Issue: 3 Pages: 576-584
  • DOI: 10.1002/jbm.a.37309
  • Peer Reviewed
• [Journal Article] The evaluation of a tissue-engineered cardiac patch seeded with hips derived cardiac progenitor cells in a rat left ventricular model (2020)
  • Author(s): Matsuzaki Yuichi、Miyamoto Shinka、Miyachi Hideki、Sugiura Tadahisa、Reinhardt James W.、Yu-Chun Chang、Zbinden Jacob、Breuer Christopher K.、Shinoka Toshiharu
  • Journal Title: PLOS ONE Volume: 15 Issue: 6 Pages: e0234087-e0234087
  • DOI: 10.1371/journal.pone.0234087
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Spontaneous reversal of stenosis in tissue-engineered vascular grafts (2020)
  • Author(s): Drews JD.、Pepper VK.、Best CA.、Szafron JM.、Cheatham JP.、Yates AR.、Hor KN.、Zbinden JC.、Chang Y、Mirhaidari GJM.、Ramachandra AB.、Miyamoto S、Blum KM.、Onwuka EA.、Zakko J、Kelly J、Cheatham SL.、King N、Reinhardt JW.、Sugiura T、Miyachi H、Matsuzaki Y、et al.
  • Journal Title: Science Translational Medicine Volume: 12 Issue: 537
  • DOI: 10.1126/scitranslmed.aax6919
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Imatinib attenuates neotissue formation during vascular remodeling in an arterial bioresorbable vascular graft. (2020)
  • Author(s): Hideki Miyachi, Shuhei Tara, Satoru Otsuru, Tai Yi, Yong-Ung Lee, Joseph D. Drews, Hidetaka Nakayama, Shinka Miyamoto, Tadahisa Sugiura, Toshihiro Shoji, Christopher K. Breuer, Toshiharu Shinoka
  • Journal Title: JVS: Vascular Science Volume: - Pages: 57-67
  • DOI: 10.1016/j.jvssci.2020.03.002
  • Peer Reviewed / Open Access