用于颞叶癫痫药理评估的三维生物打印体外癫痫模型。

IF 8.2 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Wei Chen, Ke Gai, Xiao Luo, Bing Wu, Xiu Wang, Wei Shi, Kai Zhang, Feng Lin, Wei Sun, Yu Song
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引用次数: 0

摘要

本研究介绍了一种利用三维生物打印技术的新型难治性颞叶癫痫(TLE)体外模型,旨在更准确地复制TLE的复杂神经生物学特征。我们制作了原始神经细胞构建体,并将其置于癫痫样诱导条件下,促进突触增殖和神经元缺失。系统的电生理学和免疫荧光分析表明,构建体内部存在明显的突触连接和持续的癫痫样活动,与人类癫痫模型中观察到的情况类似。值得注意的是,该模型对苯妥英和河豚毒素的治疗有反应,这说明它在药物反应动力学研究中具有潜在的实用性。此外,我们还使用 COMSOL Multiphysics 进行了药物渗透性模拟,以分析这些药物在构建体中的扩散特性。这些结果证实,我们的三维生物打印神经模型提供了一个生理上相关、伦理上可持续的平台,有利于研究TLE机制和开发具有高准确性和临床相关性的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
3D bioprintedin vitroepilepsy models for pharmacological evaluation in temporal lobe epilepsy.

This study introduces a novelin vitromodel for intractable temporal lobe epilepsy (TLE) utilizing 3D bioprinting technology, aiming to replicate the complex neurobiological characteristics of TLE more accurately. Primary neural cell constructs were fabricated and subjected to epileptiform-inducing conditions, fostering synaptic proliferation and neuronal loss. Systematically electrophysiological and immunofluorescent analyses indicated that significant synaptic connectivity and sustained epileptiform activities within the constructs akin to those observed in human epilepsy models. Notably, the model responded to treatments with phenytoin and tetrodotoxin, illustrating its potential utility in drug response kinetics studies. Furthermore, we performed drug permeability simulations using COMSOL Multiphysics to analyze the diffusion characteristics of these drugs within the constructs. These results confirm that our 3D bioprinted neural model provides a physiologically relevant and ethically sustainable platform, which is beneficial for studying TLE mechanisms and developing therapeutic strategies with high accuracy and clinical relevance.

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来源期刊
Biofabrication
Biofabrication ENGINEERING, BIOMEDICAL-MATERIALS SCIENCE, BIOMATERIALS
CiteScore
17.40
自引率
3.30%
发文量
118
审稿时长
2 months
期刊介绍: Biofabrication is dedicated to advancing cutting-edge research on the utilization of cells, proteins, biological materials, and biomaterials as fundamental components for the construction of biological systems and/or therapeutic products. Additionally, it proudly serves as the official journal of the International Society for Biofabrication (ISBF).
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