4D Cell-Condensate Bioprinting

Small. 2022 Sep;18(36):e2202196. doi: 10.1002/smll.202202196. Epub 2022 Aug 16.


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.

Keywords: 4D bioprinting; cell aggregates; hydrogels; jammed microgels; tissue engineering.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bioprinting* / methods
  • Cartilage
  • Cell Differentiation
  • Humans
  • Hydrogels
  • Microgels*
  • Printing, Three-Dimensional
  • Tissue Engineering / methods
  • Tissue Scaffolds


  • Hydrogels
  • Microgels