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Published February 15, 2022 | Version v1
Journal article Open

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

Authors/Creators

  • 1. Department of Orthopaedics University Medical Center Utrecht Utrecht University
  • 2. Department of Clinical Sciences Faculty of Veterinary Medicine Utrecht University
  • 3. Laboratory of Applied Photonics Devices École Polytechnique Fédéral Lausanne (EPFL)
  • 4. Department of Surgery Erasmus MC-University Medical Center
  • 5. Readily3D SA
  • 6. Department of Orthopaedics University Medical Center, Department of Clinical Sciences Faculty of Veterinary Medicine, Utrecht Utrecht University

Description

Organ- and tissue-level biological functions are intimately linked to micro- scale 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 mathe- matically 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 architec- tural profile of the constructs. This technology opens up new possibilities for regenerative medicine and personalized drug testing.

Notes

P.N.B. and M.B. contributed equally to this work. This project received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 949806, VOLUME-BIO) and from the European's Union's Horizon 2020 research and innovation programme under grant agreement No 964497 (ENLIGHT). R.L and J.M acknowledge the funding from the ReumaNederland (LLP-12, LLP22, and 19-1-207 MINIJOINT) and the Gravitation Program "Materials Driven Regeneration", funded by the Netherlands Organization for Scientific Research (024.003.013). R.L. also acknowledges funding from the NWA-Ideeëngenerator programme of the Netherlands Organization for Scientific Research (NWA.1228.192.105). M.B. and B.S. acknowledge funding from the research program Applied and Engineering Sciences with project number 15498, which is financed by the Netherlands Organization for Scientific Research. J.M.W. and C.M. acknowledge funding from the Swiss National Science Foundation: "Light based Volumetric printing in scattering resins" (n 200021_196971). L.J.W.vdL was supported by Medical Delta Program "Regenerative Medicine 4D". The authors would like to thank D.J. Hall from Carbon and Neon for his support with scientific illustrations, V. Onink for his assistance with the particle tracking analysis, C. Spiegel for her help with editing, Dr. K. Schneeberger, and Dr. M. Pietribiasi for the fruitful discussions.

Files

Advanced Materials - 2022 - Bernal - Volumetric Bioprinting of Organoids and Optically Tuned Hydrogels to Build Liver‐Like.pdf

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Additional details

Funding

European Commission
VOLUME-BIO - Volumetric light-driven bioprinting capturing complex physiological shape, size and function in artificial tissues and organoids 949806
European Commission
ENLIGHT - ENable LIGHT- and synthetic biology-driven volumetric bioprinting of functional human tissues 964497