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Microfluidic Droplet-Based Tailorable Porous GelMA Microspheres for 3D Spatio Controllable Cell Coculture
Advanced Materials Technologies ( IF 6.4 ) Pub Date : 2024-04-17 , DOI: 10.1002/admt.202301697
Yaolei Wang 1, 2 , Ting Du 1 , Xin Hao 1 , Yilan Wang 1, 2 , Feng Yang 1 , Huatao He 1 , Menghan Yang 1 , Meiying Hong 1 , Guanxiong Wang 1 , Hong Liu 3 , Jianxiu Guo 1
Affiliation  

For the construction of accurate 3D tissue models in vitro, the 3D coculture model formed by spatio-controlled distribution of multiple cells is essential. Despite the benefits of porous microspheres with low density, large surface area, and high permeability, exact spatio-controlled distribution fails to appear in 3D coculture models by using porous microspheres as carriers. Herein, a facile method is proposed to construct a 3D coculture model with heterogeneous cell spatio-tailored distribution using GelMA microspheres with customizable porosity structure and size based on droplet microfluidics in combination with placeholders. ATPS emulsions, containing two biocompatible immiscible aqueous phases of cell/Alg /dextran (Dex) mixture and polyethylene glycol (PEG) solution, are used as the templates to generate the placeholders. The micron-sized porous GelMA microspheres are prepared by UV crosslinking of droplets prepared in microfluidic devices, followed by chelation of the placeholders. As a proof of concept, the 3D coculture hepatocellular carcinoma (HCC) model with HepG2 encapsulated outside the pores and HUVEC inside the pores is established. Noteworthy, the cells in the 3D coculture HCC model exhibit greater cell activity and proliferation, enhanced functionalities, and drug resistance than the control group. In conclusion, this straightforward method provides a novel approach for constructing 3D coculture models in vitro.

中文翻译:


用于 3D 空间可控细胞共培养的基于微流体液滴的可定制多孔 GelMA 微球



为了构建精确的体外3D组织模型,多个细胞空间控制分布形成的3D共培养模型至关重要。尽管多孔微球具有低密度、大表面积和高渗透性的优点,但以多孔微球作为载体的3D共培养模型中未能出现精确的空间控制分布。在此,提出了一种简便的方法,使用基于液滴微流控和占位符的具有可定制孔隙结构和尺寸的 GelMA 微球来构建具有异质细胞空间定制分布的 3D 共培养模型。 ATPS 乳液含有细胞/Alg/葡聚糖 (Dex) 混合物和聚乙二醇 (PEG) 溶液的两个生物相容性不混溶水相,用作生成占位符的模板。微米级多孔 GelMA 微球是通过对微流体装置中制备的液滴进行紫外线交联,然后螯合占位符来制备的。作为概念验证,建立了 3D 共培养肝细胞癌 (HCC) 模型,其中 HepG2 封装在孔外,HUVEC 位于孔内。值得注意的是,3D 共培养 HCC 模型中的细胞比对照组表现出更高的细胞活性和增殖、增强的功能和耐药性。总之,这种简单的方法为构建体外 3D 共培养模型提供了一种新方法。
更新日期:2024-04-17
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