癌细胞和周围微环境之间的功能相互作用仍然不够了解，这促使人们对开发大量体外肿瘤模型表现出巨大兴趣。诸如营养物质和代谢物的运输、约束空间的可用性等不同参数会对肿瘤叶片的大小、形状和代谢产生影响。我们展示了基于流体力学的低成本方法，以可重复生成海藻酸和海藻酸/壳聚糖微胶囊，并将其应用于生长不同尺寸和几何学维度的人类肝癌（HepG2）球体。特别关注羟基状物质外壳的组成和厚度，有针对性地调整了微胶囊的渗透性。通过实验和模拟系统地研究了所选基准分子在外壳中的扩散，这对于确保生化物种的有效传质和/或过滤是至关重要的。通过色谱学研究代谢测定中睾酮到雄甾酮的周转，证实了微胶囊中球体的代谢活性。依据可用空间，在胶囊内观察到不同表型的3D细胞组装，变化的是细胞集合的紧密程度和它们的形状。总之，我们认为我们的系统通过便捷地调整外壳的厚度和渗透性，代表了一个有前途的平台，用于研究癌症球体的形成以及它们与周围微环境的功能相互作用。本文受版权保护。版权所有。

Functional interaction between cancer cells and the surrounding microenvironment is still not sufficiently understood, which motivates the tremendous interest for the development of numerous in vitro tumor models. Diverse parameters, e.g., transport of nutrients and metabolites, availability of space in the confinement, etc. make an impact on the size, shape, and metabolism of the tumoroids. We demonstrate the fluidics-based low-cost methodology to reproducibly generate the alginate and alginate-chitosan microcapsules and apply it to grow human hepatoma (HepG2) spheroids of different dimensions and geometries. Focusing specifically on the composition and thickness of the hydrogel shell, permeability of the microcapsules was selectively tuned. The diffusion of the selected benchmark molecules through the shell has been systematically investigated using both, experiments and simulations, which is essential to ensure efficient mass transfer and/or filtering of the biochemical species. Metabolic activity of spheroids in microcapsules was confirmed by tracking the turnover of testosterone to androstenedione with chromatography studies in a metabolic assay. Depending on available space, phenotypically different 3D cell assemblies have been observed inside the capsules, varying in the tightness of cell aggregations and their shapes. Conclusively, we believe that our system with the facile tuning of the shell thickness and permeability, represents a promising platform for studying the formation of cancer spheroids and their functional interaction with the surrounding microenvironment. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.