Laser-guided programmable construction of cell-laden hydrogel microstructures for in vitro drug evaluation

Abstract Cell-laden hydrogel microstructures have been used in broad applications in tissue engineering, translational medicine, and cell-based assays for pharmaceutical research. However, the construction of cell-laden hydrogel microstructures in vitro remains challenging. The technologies permitting generation of multicellular structures with different cellular compositions and spatial distributions are needed. Herein, we propose a laser-guided programmable hydrogel-microstructures-construction platform, allowing controllable and heterogeneous assembly of multiple cellular spheroids into spatially organized multicellular structures with good bioactivity. And the cell-laden hydrogel microstructures could be further leveraged for in vitro drug evaluation. We demonstrate that cells within hydrogels exhibit significantly higher half-maximal inhibitory concentration values against doxorubicin compared with traditional 2D plate culture. Moreover, we reveal the differences in drug responses between heterogeneous and homogeneous cell-laden hydrogel microstructures, providing valuable insight into in vitro drug evaluation.