A 4D Bio-Kirigami Strategy for Engineering Complex Tissue Curvatures

Native tissues exhibit intricate curvatures essential for their function yet recapitulating structural complexity and dynamic morphogenesis remains challenging. Here, we present a cytocompatible bio-Kirigami system that enables programmable transformation of cell-laden hydrogels into complex three-dimensional tissue constructs. The system consists of (1) a photocrosslinked hydrogel with tunable degradation and swelling behavior to drive shape transformation and (2) a rigid hydrogel frame to provide structural support. Spatial patterning encodes localized swelling differentials via sequential photolithography, enabling controlled deformation and diverse morphing behaviors. Stem cell-laden bio-Kirigami constructs underwent programmed shape transformation and developed into tissue-like structures with complex curvatures under tissue-specific culture conditions. Importantly, the engineered tissue constructs retained their structural integrity and shape after removal of the supporting frame. This bio-Kirigami strategy provides a versatile approach for engineering dynamically transformable tissue constructs that recapitulate the complex geometries of native tissues.