High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins

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 lith...

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Autores principales:	Riccardo Levato, Khoon S. Lim, Wanlu Li, Ane Urigoitia Asua, Laura Blanco Peña, Mian Wang, Marc Falandt, Paulina Nuñez Bernal, Debby Gawlitta, Yu Shrike Zhang, Tim B.F. Woodfield, Jos Malda
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Biofabrication and bioprinting Lithography Bioresin Hydrogel Digital light processing Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bbfd983502a54dfb9278db07dd27f773
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spelling	oai:doaj.org-article:bbfd983502a54dfb9278db07dd27f7732021-11-24T04:33:53ZHigh-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins2590-006410.1016/j.mtbio.2021.100162https://doaj.org/article/bbfd983502a54dfb9278db07dd27f7732021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2590006421000703https://doaj.org/toc/2590-0064Biofabrication 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 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.Riccardo LevatoKhoon S. LimWanlu LiAne Urigoitia AsuaLaura Blanco PeñaMian WangMarc FalandtPaulina Nuñez BernalDebby GawlittaYu Shrike ZhangTim B.F. WoodfieldJos MaldaElsevierarticleBiofabrication and bioprintingLithographyBioresinHydrogelDigital light processingMedicine (General)R5-920Biology (General)QH301-705.5ENMaterials Today Bio, Vol 12, Iss , Pp 100162- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biofabrication and bioprinting Lithography Bioresin Hydrogel Digital light processing Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	Biofabrication and bioprinting Lithography Bioresin Hydrogel Digital light processing Medicine (General) R5-920 Biology (General) QH301-705.5 Riccardo Levato Khoon S. Lim Wanlu Li Ane Urigoitia Asua Laura Blanco Peña Mian Wang Marc Falandt Paulina Nuñez Bernal Debby Gawlitta Yu Shrike Zhang Tim B.F. Woodfield Jos Malda High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins
description	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 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.
format	article
author	Riccardo Levato Khoon S. Lim Wanlu Li Ane Urigoitia Asua Laura Blanco Peña Mian Wang Marc Falandt Paulina Nuñez Bernal Debby Gawlitta Yu Shrike Zhang Tim B.F. Woodfield Jos Malda
author_facet	Riccardo Levato Khoon S. Lim Wanlu Li Ane Urigoitia Asua Laura Blanco Peña Mian Wang Marc Falandt Paulina Nuñez Bernal Debby Gawlitta Yu Shrike Zhang Tim B.F. Woodfield Jos Malda
author_sort	Riccardo Levato
title	High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins
title_short	High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins
title_full	High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins
title_fullStr	High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins
title_full_unstemmed	High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins
title_sort	high-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/bbfd983502a54dfb9278db07dd27f773
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High-resolution lithographic biofabrication of hydrogels with complex microchannels from low-temperature-soluble gelatin bioresins

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