Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, People's Republic of China.
Department of Laboratory Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, People's Republic of China.
Lab Chip. 2021 Sep 14;21(18):3498-3508. doi: 10.1039/d1lc00496d.
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.
3D 细胞培养物（如细胞球）广泛应用于组织工程、再生医学和转化医学，但在再现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设备，用于制造具有超越细胞结构和成分复杂性的异型细胞球。通过改变细胞悬浮液的浓度，我们可以通过无接触声辐射力精确控制由聚集的细胞球的大小。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，可可控地制造异型细胞球。这些异型细胞球可用作概念验证来模拟肿瘤组织的空间组织。我们证明了组装的组件可以根据其钙黏蛋白表达自我组装成层状结构。最后，我们展示了通过声组装将小鼠乳腺成分组装成细胞球并在培养中观察其成熟。总之，我们开发了一种声流平台来制造具有多种成分的复杂细胞球。我们设想这个平台将为球状体的高精度制造铺平道路，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。
