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基于微流控芯片的细胞机械力加载微环境构建方法

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摘要

微流控芯片具有微型化、高通量和高度可控等优势,已成为构建体外细胞力学微环境和器官芯片模型的重要平台。在细胞培养与功能研究中,机械力刺激的精准构建是模拟体内生理或病理状态(如组织间质压力、周期性压缩与拉伸)的关键因素。然而,不同类型和功能状态的细胞在力学感知机制、适宜的刺激形式及作用尺度上存在显著差异,使得“通用型”的机械力加载方案难以满足多样化的研究需求,针对目标细胞构建适宜的力学微环境十分必要。本文聚焦微流控芯片中细胞培养区域的机械力加载策略,从细胞力学需求出发,系统梳理并比较了培养基底表面刚度调控、气动驱动加载、液体介导加载以及磁场驱动软基底加载等方法在不同细胞模型中的适用性与局限性。重点分析了上皮/内皮细胞、干细胞及软骨、牙周相关细胞等在力学刺激类型、空间分布和时间加载模式方面的差异化需求,并结合典型芯片结构阐述相应施压技术的设计思路与细胞响应验证内容,旨在为特定细胞类型的力学研究和器官芯片设计提供参考,以推动微流控力学微环境构建向更高生理相关性方向发展。

Abstract

Microfluidic chips, owing to their advantages of miniaturization, high throughput, and precise controllability, have become important platforms for constructing in vitro cellular mechanical microenvironments and organ-on-a-chip models. In cell culture and functional studies, the precise generation of mechanical stimuli is a key factor in recapitulating physiological or pathological conditions in vivo, such as interstitial tissue pressure, cyclic compression, and cyclic stretching. However, cells of different types and functional states exhibit substantial differences in mechanosensing mechanisms, appropriate forms of mechanical stimulation, and effective loading scales. Therefore, universal mechanical loading strategies are often insufficient to meet diverse research needs, making it essential to construct tailored mechanical microenvironments for specific target cells. This review focuses on mechanical loading strategies applied to the cell culture regions of microfluidic chips. Starting from the mechanical requirements of cells, it systematically summarizes and compares the applicability and limitations of various approaches in different cell models, including modulation of culture substrate surface stiffness, pneumatically driven loading, liquid-mediated loading, and magnetic field-driven soft-substrate loading. Particular attention is given to the distinct requirements of epithelial/endothelial cells, stem cells, chondrocytes, and periodontal-related cells in terms of mechanical stimulus type, spatial distribution, and temporal loading patterns. In combination with representative chip architectures, this review further discusses the design principles of corresponding pressure-application techniques and the validation of cellular responses. It aims to provide a reference for mechanobiological studies of specific cell types and the design of organ-on-a-chip systems, thereby promoting the development of microfluidic mechanical microenvironments with enhanced physiological relevance.

Contents

1 Introduction

2 Substrate surface stiffness modulation techniques

2.1 Core principle

2.2 Surface stiffness modulation strategies and cellular mechanosensory responses

3 Pneumatically driven mechanical loading techniques

3.1 Core principle

3.2 Common architectures and operating modes of pneumatically driven mechanical loading chips

4 Liquid-mediated mechanical loading techniques

4.1 Core principle

4.2 Common chip architectures and loading modes for liquid-mediated mechanical stimulation

4.3 Osmotic modulation of the cellular mechanical microenvironment

5 Magnetic field-driven soft-substrate mechanical loading techniques

5.1 Core principle

5.2 Microfluidic chip architectures and mechanical loading modes based on magnetically responsive soft substrates

6 Cellular responses induced by different mechanical loading modalities

7 Conclusion

关键词

微流控芯片 / 机械力加载 / 细胞力学刺激 / 细胞力学感知 / 细胞力学微环境

Key words

microfluidic chip / mechanical loading / cellular mechanical stimulation / cellular mechanosensing / cellular mechanical microenvironment

引用本文

引用格式 ▾
姜迪, 蔡佳峰, 陆玲波, 谢理哲, 吴斌, 严斌. 基于微流控芯片的细胞机械力加载微环境构建方法[J]. 化学进展, , (): 0 DOI:10.7536/PC20260423
Di Jiang, Jiafeng Cai, Lingbo Lu, Lizhe Xie, Bin Wu, Bin Yan. Progress in Chemistry 0 DOI:10.7536/PC20260423

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基金资助

国家重点研发计划项目(SQ2023YFC2400025)

国家自然科学基金项目(51805270)

国家自然科学基金项目(82371000)

国家自然科学基金项目(82571135)

国家自然科学基金项目(82571165)

江苏省重点研发计划项目(BE2023836)

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