摘要
肿瘤微环境的力学性质对肿瘤细胞的增殖、侵袭等行为具有重要影响。目前体外研究微环境力学性质的方法大多局限于水凝胶的弹性响应,不能反映真实组织的粘弹性力学特征,且无法实现长期稳定的动态细胞培养。针对上述问题,本研究基于毛细爆破微阀结构,设计了仿肿瘤微环境的芯片结构,制备了离子交联与共价交联混合的海藻酸钠水凝胶,测定表明其粘弹性特征符合肿瘤微环境力学性能需求,确定了剪切模量在0.306~3.238 kPa范围内具有粘度梯度的水凝胶的制备方法。基于多孔介质扩散的Fick定律,通过有限元仿真与微流体实验对芯片内的交联过程进行了优化设计,得到了具有良好线性度的交联剂浓度梯度。在芯片的粘弹性梯度区域内进行HeLa细胞培养实验,结果表明HeLa细胞在具有粘性特征的软基质上具有更强的转移能力,证明了粘弹性梯度微流控芯片的功能性,为肿瘤转移研究提供了稳定可控的体外实验平台。
The mechanical properties of the tumor microenvironment have an important impact on the proliferation,invasion,and other behaviors of tumor cells.Most of the current in vitro methods to study the mechanical properties of the microenvironment are limited to the elastic response of hydrogels,which cannot reflect the viscoelastic mechanical characteristics of real tissues and cannot realize long-term stable dynamic cell culture.To address the above problems,a chip structure imitating the tumor microenvironment was designed based on the capillary burst microvalve structure,a sodium alginate hydrogel mixed with ionic crosslinking and covalent crosslinking was prepared,whose viscoelastic characteristics were determined to be in line with the demand for mechanical properties of the tumor microenvironment,and a hydrogel preparation method with a viscosity gradient in the range of shear modulus of 0.306-3.238 kPa was identified.Based on Fick's law of diffusion in porous media,the cross-linking process within the chip was optimally designed by finite element simulation and microfluidic experiments,resulting in a cross-linker concentration gradient with good linearity.The HeLa cell culture experiments were performed in the viscoelastic gradient region of the chip,and the results showed that HeLa cells had a stronger metastatic ability on the soft matrix with viscous characteristics,proving the functionality of the viscoelastic gradient microfluidic chip.It provides a stable and controllable in vitro experimental platform for tumor metastasis research.
作者
王钟禹
丁来钱
刘冲
李经民
WANG Zhongyu;DING Laiqian;LIU Chong;LI Jingmin(School of Mechanical Engineering,Dalian University of Technology,Dalian 116024,China;Key Lab for Micro/Nano Technology and System of Liaoning Province,Dalian 116024,China)
出处
《分析试验室》
北大核心
2025年第8期1131-1138,共8页
Chinese Journal of Analysis Laboratory
基金
国家自然科学基金(51875084)资助。
关键词
肿瘤微环境
微流控芯片
水凝胶
细胞外基质
粘弹性梯度
tumor microenvironment
microfluidic chip
hydrogel
extracellular matrix
viscoelastic gradient
作者简介
王钟禹,男(2000-),硕士研究生。研究方向:微纳制造,zhongyuw@mail.dlut.edu.cn;通信作者:李经民,男(1979-),博士,教授。研究方向:微机电系统(MEMS),jingminl@dlut.edu.cn。
