Volumetric Bioprinting of Organoids and Optically Tuned Hydrogels to Build Liver‐Like Metabolic Biofactories

• Published in: Advanced materials (Weinheim) Vol. 34; no. 15; pp. e2110054 - n/a
• Main Authors: Bernal, Paulina Nuñez, Bouwmeester, Manon, Madrid‐Wolff, Jorge, Falandt, Marc, Florczak, Sammy, Rodriguez, Nuria Ginés, Li, Yang, Größbacher, Gabriel, Samsom, Roos‐Anne, van Wolferen, Monique, van der Laan, Luc J. W., Delrot, Paul, Loterie, Damien, Malda, Jos, Moser, Christophe, Spee, Bart, Levato, Riccardo
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.04.2022
• Subjects: Albumins; Ammonia; Bioengineering; biofabrication; Bioprinting - methods; bioresins; Cellular structure; Enzyme activity; Gelatin; Gelatin - chemistry; Humans; Hydrogels; Hydrogels - chemistry; Lattices (mathematics); light‐based 3D printing; Liver; Metabolism; Organoids - metabolism; Printing, Three-Dimensional; Refractivity; Stem cells; Stiffness; Three dimensional printing; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds - chemistry; Tortuosity; volumetric additive manufacturing; bioresins; biofabrication; hydrogels; light-based 3D printing; volumetric additive manufacturing
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202110054

Organ‐ and tissue‐level biological functions are intimately linked to microscale cell–cell interactions and to the overarching tissue architecture. Together, biofabrication and organoid technologies offer the unique potential to engineer multi‐scale living constructs, with cellular microenvironments formed by stem cell self‐assembled structures embedded in customizable bioprinted geometries. This study introduces the volumetric bioprinting of complex organoid‐laden constructs, which capture key functions of the human liver. Volumetric bioprinting via optical tomography shapes organoid‐laden gelatin hydrogels into complex centimeter‐scale 3D structures in under 20 s. Optically tuned bioresins enable refractive index matching of specific intracellular structures, countering the disruptive impact of cell‐mediated light scattering on printing resolution. This layerless, nozzle‐free technique poses no harmful mechanical stresses on organoids, resulting in superior viability and morphology preservation post‐printing. Bioprinted organoids undergo hepatocytic differentiation showing albumin synthesis, liver‐specific enzyme activity, and remarkably acquired native‐like polarization. Organoids embedded within low stiffness gelatins (<2 kPa) are bioprinted into mathematically defined lattices with varying degrees of pore network tortuosity, and cultured under perfusion. These structures act as metabolic biofactories in which liver‐specific ammonia detoxification can be enhanced by the architectural profile of the constructs. This technology opens up new possibilities for regenerative medicine and personalized drug testing. Visible‐light‐driven volumetric bioprinting enables the layerless fabrication of constructs embedding human liver organoids. Bioresins with tunable refractive index allow printing of centimeter‐scale tissue analogs at high cell density in below 20 s. Organoids mature into hepatocytic structures with native‐like polarization. Bioprinted mathematically defined architectures modulate liver functions such as ammonia detoxification in a geometry‐dependent manner, opening new possibilities for liver biofabrication.