Scaffold-free generation of heterotypic cell spheroids using acoustofluidics,Lab on a Chip

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Scaffold-free generation of heterotypic cell spheroids using acoustofluidics
Lab on a Chip ( IF 6.1 ) Pub Date : 2021-07-26 , DOI: 10.1039/d1lc00496d
Zhuhao Wu ₁ , Bin Chen ₂ , Yue Wu ₁ , Yu Xia ₁ , Hui Chen ₁ , Zhiyi Gong ₁ , Hang Hu ₃ , Zhao Ding ₃ , Shishang Guo ₁

Affiliation

3D cell cultures such as cell spheroids are widely used for tissue engineering, regenerative medicine, and translational medicine, but challenges remain in recapitulating the architectural complexity and spatiotemporal heterogeneity of tissues. Thus, we developed a scaffold-free and versatile acoustofluidic device to fabricate heterotypic cell spheroids with complexity over cell architectures and components. By varying the concentrations of cell suspension, we can precisely control the size of spheroids aggregated by a contact-free acoustic radiation force. By tuning the cell components including tumor cells, fibroblasts, and endothelial cells, heterotypic spheroids were controllably fabricated. These heterotypic spheroids can be used as a proof-of concept to model the spatial organization of tumor tissues. We demonstrated that the assembled components can self-assemble into layered structures as instructed by their cadherin expression. Finally, we demonstrated the acoustic assembly of mouse mammary gland components into spheroids and observed their maturation in culture. To conclude, we developed an acoustofluidic platform to fabricate complex spheroids with multiple components. We envision that this platform will pave the way for the high accuracy of spheroid fabrication and offer broad applications in numerous areas, such as tumor research, tissue engineering, developmental biology, and drug discovery.

中文翻译：

使用声流体学无支架生成异型细胞球体

细胞球体等 3D 细胞培养物广泛用于组织工程、再生医学和转化医学，但在概括组织的结构复杂性和时空异质性方面仍然存在挑战。因此，我们开发了一种无支架且多功能的声流体装置，用于制造具有复杂细胞结构和组件的异型细胞球体。通过改变细胞悬液的浓度，我们可以精确控制由非接触声辐射力聚集的球体的大小。通过调整包括肿瘤细胞、成纤维细胞和内皮细胞在内的细胞成分，可以可控地制造异型球体。这些异型球体可用作概念验证来模拟肿瘤组织的空间组织。我们证明组装的组件可以按照其钙粘蛋白表达的指示自组装成分层结构。最后，我们展示了小鼠乳腺成分的声学组装成球体，并观察了它们在培养中的成熟。总之，我们开发了一个声流体平台来制造具有多个组件的复杂球体。我们设想该平台将为球体制造的高精度铺平道路，并在肿瘤研究、组织工程、发育生物学和药物发现等众多领域提供广泛的应用。我们开发了一个声流体平台来制造具有多个组件的复杂球体。我们设想该平台将为球体制造的高精度铺平道路，并在肿瘤研究、组织工程、发育生物学和药物发现等众多领域提供广泛的应用。我们开发了一个声流体平台来制造具有多个组件的复杂球体。我们设想该平台将为球体制造的高精度铺平道路，并在肿瘤研究、组织工程、发育生物学和药物发现等众多领域提供广泛的应用。

更新日期：2021-08-04

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