Discrete 2D Material Programming for 3D Shaping and Morphogenesis-Inspired 4D Bioprinting.

Programming in-plane growth in thin sheets enables 2-to-3D shape transformation into doubly curved morphologies common in living organisms. Despite its morphogenesis-inspired premise and intrinsic suitability for tissue-like systems, translating growth-programmed shaping into engineered living constructs remains challenging. Here, we report cell-compatible discrete 2D material programming for growth-driven 3D shaping and morphogenesis-inspired 4D bioprinting. By patterning cell-supportive microdomains within a responsive hydrogel matrix, we program in-plane growth to prescribe target metrics. This approach enables 4D bioprinting of living constructs that autonomously transform into prescribed 3D morphologies under physiological conditions. We establish design rules that expand the programmable 3D shape space, characterize time-dependent morphing dynamics, and demonstrate bioinspired motions. The transformed constructs maintain high cell viability and support tissue-relevant cellular behaviors. Cell-compatible discrete 2D material programming provides a platform for programmable morphogenesis and dynamic biofabrication, with potential relevance to hybrid living-synthetic systems, including bioinspired soft robotics, engineered tissue constructs, and cell-based devices.