Programmable 3D cell alignment of bioprinted tissue via soft robotic dynamic stimulation

Recent breakthroughs in biofabrication have enabled the development of engineered tissues for various organ systems, supporting applications in drug testing and regenerative medicine. However, current approaches do not allow for dynamic mechanical maturation of engineered tissue in 3D. Although uniaxial mechanostimulation techniques have shown promise in generating anisotropic tissues, they fail to recapitulate the biomechanics of complex tissues. As a result, existing biofabricated tissues lack the ability to replicate complex 3D alignment patterns essential for functional biomimicry. Here, we present a soft robotics-driven approach for programmable 3D alignment in 3D bioprinted tissue. Our method introduces the co-printing of biological tissue with a silicone-based soft robot via a custom core-double shell nozzle. The application of 3D, exogenous, dynamic expansion and torsional forces to the tissue via the co-printed silicone robot was found to drive cell alignment. Confocal imaging revealed pronounced anisotropy of the stimulated tissue samples compared to the unstimulated controls. In addition, different cellular orientation patterns resulted from each mode of stimulation, demonstrating the versatility of the soft robotic approach in tailoring the pattern of tissue alignment based on programmed mechanostimulation.