4D Cell-Condensate Bioprinting

4D bioprinting techniques that facilitate formation of shape-changing scaffold-free cell condensates with prescribed geometries have yet been demonstrated. Here, a simple 4D bioprinting approach is presented that enables formation of a shape-morphing cell condensate-laden bilayer system. The strategy produces scaffold-free cell condensates which morph over time into predefined complex shapes. Cell condensate-laden bilayers with specific geometries are readily fabricated by bioprinting technologies. The bilayers have tunable deformability and microgel (MG) degradation, enabling controllable morphological transformations and on-demand liberation of deformed cell condensates. With this system, large cell condensate-laden constructs with various complex shapes are obtained. As a proof-of-concept study, the formation of the letter "C"- and helix-shaped robust cartilage-like tissues differentiated from human mesenchymal stem cells (hMSCs) is demonstrated. This system brings about a versatile 4D bioprinting platform idea that is anticipated to broaden and facilitate the applications of cell condensation-based 4D bioprinting.