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微流体人体体模拟肝脏模型作为药物诱导肝损伤查平台

Souradeep Dey¹, Amritha Bhat², G Janani²

¹Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India.

|June 1, 2024

概括

一个新的3D生物打印的人类肝脏瘤模型 (HPLAM) 在体外准确预测药物诱导的肝损伤 (DILI). 这种先进的模型克服了动物研究的局限性,以更好地评估药物安全性.

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.
毒理学毒理学毒理学

背景情况:

临床前动物模型无法预测药物诱导性肝损伤 (DILI),导致临床试验失败和药物撤销.
对于与人类相关的体外模型来准确预测各种DILI表型的需求至关重要.

研究的目的:

使用3D打印和微流体学开发一个人体仿真肝模型 (HPLAM).
评估HPLAM在预测与人类临床结果相关的DILI表型方面的能力.

主要方法:

基于猪肝细胞外矩阵 (ECM) 的生物材料墨水的配方.
使用3D打印和微流体技术对HPLAM进行生物工程,以模仿本地肝脏的结构和功能.
在一个生理相关的微环境下,在HPLAM中培养人类衍生肝细胞.

主要成果:

HPLAM成功地重现了辐射性肝状结构和功能性鼻状微血管.
在HPLAM中,人类衍生肝细胞表现出增强的肝功能,分泌物水平和生物标志物表达.
HPLAM重现了与人类DILI相关的剂量和时间依赖的肝毒性反应,表现优于常规静态培养.

结论:

开发的HPLAM在体内类似的肝功能和微环境中模拟.
惠普拉姆是体外DILI风险评估的一个有前途的平台,改善药物安全性评估和降低人类风险.

关键词:

通过3D打印打印3D打印.细胞教学生物材料墨水药物诱导的肝损伤是药物诱导的肝损伤.药物查是指对药物进行查.肝毒性肝毒性肝毒性人类肝脏模型模型物理模拟微流体装置是一种物理模拟微流体装置.

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