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Highly heterogeneous structures are closely related to the realization of the tissue functions of living organisms. However, precisely controlling the assembly of heterogeneous structures is still a crucial challenge. This work presents an on-demand bubble-assisted acoustic method for active cell patterning to achieve high-precision heterogeneous structures. Active cell patterning is achieved by the combined effect of acoustic radiation forces and microstreaming around oscillating bubble arrays. On-demand bubble arrays allow flexible construction of cell patterns with a precision of up to 45 μm. As a typical example, the in vitro model of hepatic lobules, composed of patterned endothelial cells and hepatic parenchymal cells, was constructed and cultured for 5 days. The good performance of urea and albumin secretion, enzymatic activity and good proliferation of both cells prove the feasibility of this technique. Overall, this bubble-assisted acoustic approach provides a simple and efficient strategy for on-demand large-area tissue construction, with considerable potential for different tissue model fabrication.

Graphical abstract: Heterogeneous tissue construction by on-demand bubble-assisted acoustic patterning

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