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In this study, we report a rational and robust methodology to construct three dimensional (3D) tubular-structures solely by self-assembly of vascular mesenchymal cells (VMCs). Using the cell-laden hyaluronic acid hydrogel surrounded by cell-free gel with a higher stiffness, VMCs spontaneously migrated across the interface and assembled into 3D tubes, which composes of numerous cells. Based on turing instability which describes the reaction-diffusion processes of inhibitors and activators, this result of 3D tubular structure formation agrees with theoretical predictions from simulations of the reaction-diffusion of morphogens and cells under the initial conditions of patterned cell-laden hydrogel. We showed that this combination of theoretical prediction and experiments is able to produce multi-cellular 3D tubes with desired dimensions and determinate orientation in hydrogel mimicking the 3D features of tubular tissue. This work provides a reliable methodology for creating tubular structures with controllable sizes inside the 3D hydrogel through multi-cellular self-organization.

Xiaolu Zhu, Shiva Gojgini, Ting-Hsuan Chen, Fang Teng, Peng Fei, Siyan Dong, Tatiana Segura, Chih-Ming Ho

Zhu, X; Gojgini, S; Chen, T-H; Teng, F; Fei, P; Dong, S; Segura, T; Ho, C-M