Single-Step Biofabrication of In Situ Spheroid-Forming Compartmentalized Hydrogel for Clinical-Sized Cartilage Tissue Formation

Bas van Loo, Maik Schot, Melvin Gurian, Tom Kamperman, Jeroen Leijten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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3D cellular spheroids offer more biomimetic microenvironments than conventional 2D cell culture technologies, which has proven value for many tissue engineering applications. Despite beneficiary effects of 3D cell culture, clinical translation of spheroid tissue engineering is challenged by limited scalability of current spheroid formation methods. Although recent adoption of droplet microfluidics can provide a continuous production process, use of oils and surfactants, generally low throughput, and requirement of additional biofabrication steps hinder clinical translation of spheroid culture. Here, the use of clean (e.g., oil-free and surfactant-free), ultra-high throughput (e.g., 8.5 mL min−1, 10 000 spheroids s−1), single-step, in-air microfluidic biofabrication of spheroid forming compartmentalized hydrogels is reported. This novel technique can reliably produce 1D fibers, 2D planes, and 3D volumes compartmentalized hydrogel constructs, which each allows for distinct (an)isotropic orientation of hollow spheroid-forming compartments. Spheroids produced within ink-jet bioprinted compartmentalized hydrogels outperform 2D cell cultures in terms of chondrogenic behavior. Moreover, the cellular spheroids can be harvested from compartmentalized hydrogels and used to build shape-stable centimeter-sized biomaterial-free living tissues in a bottom-up manner. Consequently, it is anticipated that in-air microfluidic production of spheroid-forming compartmentalized hydrogels can advance production and use of cellular spheroids for various biomedical applications.

Original languageEnglish
Article number2300095
Number of pages10
JournalAdvanced healthcare materials
Issue number27
Early online date26 Oct 2023
Publication statusPublished - 27 Oct 2023


  • aggregate
  • biofabrication
  • cell encapsulation
  • compartmentalized hydrogels
  • in-air microfluidics
  • microfluidics
  • spheroids
  • UT-Hybrid-D


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