TY - JOUR
T1 - Scaffold-free generation of heterotypic cell spheroids using acoustofluidics
AU - Wu, Zhuhao
AU - Chen, Bin
AU - Wu, Yue
AU - Xia, Yu
AU - Chen, Hui
AU - Gong, Zhiyi
AU - Hu, Hang
AU - Ding, Zhao
AU - Guo, Shishang
N1 - Publisher Copyright:
© The Royal Society of Chemistry 2021.
PY - 2021/9/21
Y1 - 2021/9/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85114904135&partnerID=8YFLogxK
U2 - 10.1039/d1lc00496d
DO - 10.1039/d1lc00496d
M3 - Article
C2 - 34346468
AN - SCOPUS:85114904135
SN - 1473-0197
VL - 21
SP - 3498
EP - 3508
JO - Lab on a Chip
JF - Lab on a Chip
IS - 18
ER -