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变相酸盐大分子与氧化性胰腺小岛损伤作斗争,使小岛植入和在奥门中发挥作用

Jacqueline A Burke^1,2, Yunxiao Zhu^1,2, Xiaomin Zhang^2,3

¹Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA.

Science advances

|June 7, 2024

概括

一种新的水凝,PPCN,保护胰腺小岛免受氧化应激,并改善慢性胰腺炎移植后的移植. 这种抗氧化剂大分子支持在临床前模型中长期控制血糖.

科学领域:

生物材料科学生物材料科学
再生医学是一种再生医学.
岛屿生物学岛屿生物学

背景情况:

慢性胰腺炎 (CP) 的全胰腺切除,其次是宫内小岛自移植 (TP-IAT) 的结果低于最佳.
胰腺炎症,岛屿隔离期间的氧化应激和肝血管构成了岛屿移植和功能方面的挑战.
目前的方法缺乏有效的策略来保持小岛的氧化还原状态,并促进成功的肝外移植.

研究的目的:

开发和评估一种热敏,抗氧化大分子,PPCN,以提高小岛的生存和功能.
评估PPCN能够保护小岛免受氧化应激,并促进肝外体移植的能力.
在非人类灵长类动物 (NHP) 模型中研究PPCN介导的小岛自移植的疗效.

主要方法:

聚乙烯甘醇酸-co-N-异烯胺 (PPCN) 的合成和表征,是一种热敏水凝.
在体外评估PPCN对氧化应激小岛的保护作用.
评估PPCN介导的小岛植入和功能在自主移植后的NHPs的预兆.

主要成果:

PPCN有效地保护小岛免受氧化应激,保持其功能和生存能力.
在体温下,PPCN从液体转化为水凝,封装了小岛.
用PPCN封装的小岛移植NHP的转移导致持续的正常血糖症超过100天,胰岛素支持最小.
在NHP预兆中,PPCN耐受性很好,在没有显著纤维化的情况下显示再吸收.

结论:

PPCN是一种有前途的生物材料,可以保护小岛的功能并增强TP-IAT的植入.
PPCN的抗氧化特性有助于维护小岛功能,解决当前TP-IAT协议的关键局限性.
这项临床前研究为使用PPCN治疗慢性胰腺炎患者TP-IAT的临床转化提供了强有力的支持.

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