全水相微流控系统一步制备球丝异质载体用作细胞三维培养  

One-step generation of droplet-filled hydrogel microfibers for3D cell culture using an all-aqueous microfluidic system

作　　者：赵孟乾 刘海涛 张旭[1] 甘忠桥 秦建华[1,2] ZHAO Mengqian;LIU Haitao;ZHANG Xu;GAN Zhongqiao;QIN Jianhua(Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian 116023,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院大连化学物理研究所,辽宁大连116023 [2]中国科学院大学,北京100049

出　　处：《色谱》2023年第9期742-751,共10页Chinese Journal of Chromatography

基　　金：国家重点研发计划项目(2022YFA1205000);国家自然科学基金(82102229).

摘　　要：水凝胶微丝是一种在生物医学领域备受关注的支架材料,具有良好的生物相容性、可调的力学性能和较大的比表面积。然而,在绿色环境下制备高细胞负载能力和多组分载荷的异质微丝仍然面临挑战。为了克服这一问题,本研究建立了一种基于气动泵阀辅助的全水相微流控系统,该系统能够实现具有球丝异质形态和先进功能的水凝胶微载体的一步制备。在这个系统中,利用右旋糖酐和聚乙二醇两相的自发相分离,形成液滴,并利用海藻酸钠和氯化钙的离子交联固化,形成水凝胶。通过调整内相、中间相和外相的流速,可以灵活控制液滴的大小、液滴之间的间距和微丝的宽度。得到的水凝胶微丝具有等距离排列的液滴,呈现出球丝异质的形态。进一步的实验结果表明,这种水凝胶微丝载体可以用于高通量原位生成三维细胞球。生成的细胞球表现出良好的细胞存活率和药物测试功能。这说明该载体在细胞培养方面具有潜在的应用前景。该全水相微流控系统具有高效、精确和可控的特点,为水凝胶微丝的制备提供了新的方法。这一技术的开发为进一步开展生物医学研究和应用提供了有力支持,也为制备用于材料科学、组织工程和药物测试的多功能水凝胶微丝提供了新途径。Hydrogel microfibers,which are characterized by flexible mechanical properties,a uniform spatial distribution,large surface areas,and excellent biocompatibility,hold great potential for various biomedical applications.However,the fabrication of heterogeneous hydrogel microfibers with high cell-loading capacity and the ability to carry multiple components via an environmentally friendly method remains challenging.In this study,we developed a novel pneumatic pump-assisted all-aqueous microfluidic system that enables the one-step fabrication of all-aqueous droplet-filled hydrogel microfibers with unique morphologies and adjustable configurations.By designing a pump-valve cycling system and selecting two immiscible fluids with stable water interfaces(dextran and polyethylene glycol),we successfully fabricated alginate microfibers with equidistantly arranged droplets through the ionotropic gelation reaction between sodium alginate and calcium chloride.The droplet size,interdroplet spacing,and microfiber dimensions could be flexibly controlled by adjusting the flow rates of the inner-phase,middle-phase,and outer-phase inlets.The results showed that the system enabled the high-throughput in situ formation of functional three-dimensional cell spheroids.The generated cell spheroids exhibited excellent cell viability and drug-testing functionality,indicating their potential applications in cell cultures.The developed technique offers strong support for future biomedical research and applications,and provides a new approach for the preparation of multifunctional hydrogel microfibers for materials science,tissue engineering,and drug testing.

关 键 词：全水相微流控系统 球丝异质载体 细胞载体 

分 类 号：O658[理学—分析化学]