High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins
Levato, Riccardo; Lim, Khoon S; Li, Wanlu; Asua, Ane Urigoitia; Peña, Laura Blanco; Wang, Mian; Falandt, Marc; Bernal, Paulina Nuñez; Gawlitta, Debby; Zhang, Yu Shrike; Woodfield, Tim B F; Malda, Jos
(2021) Materials Today Bio, volume 12, pp. 1 - 13
(Article)
Abstract
Biofabrication via light-based 3D printing offers superior resolution and ability to generate free-form architectures, compared to conventional extrusion technologies. While extensive efforts in the design of new hydrogel bioinks lead to major advances in extrusion methods, the accessibility of lithographic bioprinting is still hampered by a limited choice of cell-friendly
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resins. Herein, we report the development of a novel set of photoresponsive bioresins derived from ichthyic-origin gelatin, designed to print high-resolution hydrogel constructs with embedded convoluted networks of vessel-mimetic channels. Unlike mammalian gelatins, these materials display thermal stability as pre-hydrogel solutions at room temperature, ideal for bioprinting on any easily-accessible lithographic printer. Norbornene- and methacryloyl-modification of the gelatin backbone, combined with a ruthenium-based visible light photoinitiator and new coccine as a cytocompatible photoabsorber, allowed to print structures resolving single-pixel features (∼50 μm) with high shape fidelity, even when using low stiffness gels, ideal for cell encapsulation (1-2 kPa). Moreover, aqueous two-phase emulsion bioresins allowed to modulate the permeability of the printed hydrogel bulk. Bioprinted mesenchymal stromal cells displayed high functionality over a month of culture, and underwent multi-lineage differentiation while colonizing the bioresin bulk with tissue-specific neo-deposited extracellular matrix. Importantly, printed hydrogels embedding complex channels with perfusable lumen (diameter <200 μm) were obtained, replicating anatomical 3D networks with out-of-plane branches (i.e. brain vessels) that cannot otherwise be reproduced by extrusion bioprinting. This versatile bioresin platform opens new avenues for the widespread adoption of lithographic biofabrication, and for bioprinting complex channel-laden constructs with envisioned applications in regenerative medicine and hydrogel-based organ-on-a-chip devices.
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Keywords: Biofabrication and bioprinting, Bioresin, Digital light processing, Hydrogel, Lithography, Bioengineering, Molecular Biology, Biotechnology, Biomedical Engineering, Cell Biology, Biomaterials, Journal Article
ISSN: 2590-0064
Publisher: Elsevier
Note: Funding Information: 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). R.L and J.M acknowledge the funding from the ReumaNederland ( LLP-12 , LLP22 , and 19-1-207 MINIJOINT), the Gravitation Program “Materials Driven Regeneration”, funded by the Netherlands Organization for Scientific Research ( 024.003.013 ), and the osteochondral defect collaborative research program supported by the AO Foundation (Davos, Switzerland). Y.S.Z. acknowledges the support by the National Science Foundation ( NSF-CBET-EBMS-1936105 ) and the Brigham Research Institute. K.S.L. acknowledges funding by New Zealand Health Research Council (Emerging Researcher First Grant – 15/483 , Sir Charles Hercus Health Research Fellowship – 19/135) and Royal Society of New Zealand (Marsden Fast Start – MFP-UOO1826 ). T.W. acknowledges the Royal Society Te Apārangi Rutherford Discovery Fellowship ( RDF-UOO1204 ), the Medical Technologies Centre of Research Excellence (MedTech CoRE), and the Ministry for Business, Innovation & Employment ( UOOX1409 ). Funding Information: 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). R.L and J.M acknowledge the funding from the ReumaNederland (LLP-12, LLP22, and 19-1-207 MINIJOINT), the Gravitation Program ?Materials Driven Regeneration?, funded by the Netherlands Organization for Scientific Research (024.003.013), and the osteochondral defect collaborative research program supported by the AO Foundation (Davos, Switzerland). Y.S.Z. acknowledges the support by the National Science Foundation (NSF-CBET-EBMS-1936105) and the Brigham Research Institute. K.S.L. acknowledges funding by New Zealand Health Research Council (Emerging Researcher First Grant ? 15/483, Sir Charles Hercus Health Research Fellowship ? 19/135) and Royal Society of New Zealand (Marsden Fast Start ? MFP-UOO1826). T.W. acknowledges the Royal Society Te Ap?rangi Rutherford Discovery Fellowship (RDF-UOO1204), the Medical Technologies Centre of Research Excellence (MedTech CoRE), and the Ministry for Business, Innovation & Employment (UOOX1409). Publisher Copyright: © 2021
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