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腱断裂の治療における足場・接着剤としてのフィブリンの研究

上原, 浩介 東京大学 DOI:10.15083/0002006109

2023.03.20

概要

【別紙 2】
審査の結果の要旨
⽒名 上原 浩介
本研究では、研究1では、腱修復における細胞移植の足場としてのフィブリ
ンの有用性を、接着剤としての生体力学的視点、細胞培養環境としての細胞生
物学的視点から検討し、研究2では、接着剤としてのフィブリンが、peripheral
sutureの代替になりえるかどうかを、滑走抵抗試験などを用いて検証してあ
り、下記の結果が得られている。

1. イヌ腱修復モデルにおいて、高い濃度のフィブリノーゲンから生成した
フィブリンが高い破断強度、破断ストレス、伸張剛性、圧縮剛性を有す
るものの臨床上要求される強度に及ばない。
2. フィブリノーゲン40 mg/ml未満から生成されたフィブリン内で培養した群
は細胞形態が紡錘形で突起を有していたが、80 mg/mlの群では円形を呈し
ており、トロンビンの濃度は細胞形態に影響なかった。
3. scratch assayにおいて80 ml/mlフィブリノーゲンから生成されたフィブリン
の群では細胞の遊走が抑制され、40 ml/mlフィブリノーゲンから生成され
たフィブリンの群では細胞の遊走が抑制されず、トロンビン濃度は遊走
能に影響を与えなかった。
4. フィブリンをperipheral sutureの代わりに接着剤として使用した場合に、潤
滑剤を加えても最大滑走抵抗は低くならない。

5. 潤滑剤は平均滑走抵抗を改善することが既報から明らかにされている
が、腱縫合においてより重要とされる最大滑走抵抗は改善しない
6. core sutureに潤滑剤を使用してもperipheral sutureを省略できるほどの最大
滑走抵抗の改善は得られない。

以上、本論文は腱縫合のモデルを用い、組織工学の足場、接着剤として働く
フィブリンの役割を生体力学的、細胞生物学的視点から明らかにした。いまだ
安定して良好な成績を得るのが困難な腱断裂の治療において、重要な貢献をな
すと考えらえる。以上より、本論文は博士(医学)の学位授与に値すると認め
られる。

よって、博士(医学)の学位請求論文として合格と認められる。

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