Facile Single‐Nanocomposite 4D Bioprinting of Dynamic Hydrogel Constructs with Thickness‐Controlled Gradient

The advent of 4D bioprinting has fueled significant progress in tissue engineering, but it faces major challenges such as limited options of smart bioinks and complexity of designing printing paths, limiting its broader application in tissue engineering. In this study, a smart composite hydrogel is first developed by combining gelatin, gelatin methacryloyl, and MXene (MX/GG), exhibiting excellent printability and shape-morphing capabilities. A facile and robust 4D printing strategy is proposed to fabricate MX/GG hydrogels with distinct spatial crosslinking gradients by simply tuning the domain-specific pattern thickness followed by a single UV exposure. Finite element analysis is applied to effectively guide the thickness-controlled shape-morphing process, resulting in precise alignment with the actual curved constructs and reliably predicting the shape transformation of CAD-designed patterns. Inspired by natural shape-morphing systems, a wide range of biomimetic constructs are successfully 4D printed, including unidirectional curved constructs (e.g., five-petal flower) and bidirectional curved constructs (e.g., scorpion). As a proof-of-concept, cell-laden MX/GG bioinks are 4D bioprinted into humidity-driven self-folding strips. Living cells experienced bending-associated strain within 3D constructs and proliferated and functioned effectively. Developed with the facile 4D printing strategy, the MXene-reinforced smart hydrogels hold significant promise for the biofabrication of diverse programmable dynamic tissues and organs.