Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures
Abstract Three-dimensional hydrogel-based organ-like cultures can be applied to study development, regeneration, and disease in vitro. However, the control of engineered hydrogel composition, mechanical properties and geometrical constraints tends to be restricted to the initial time of fabrication....
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-37953-4 |
| _version_ | 1827933269878898688 |
|---|---|
| author | Anna Urciuolo Giovanni Giuseppe Giobbe Yixiao Dong Federica Michielin Luca Brandolino Michael Magnussen Onelia Gagliano Giulia Selmin Valentina Scattolini Paolo Raffa Paola Caccin Soichi Shibuya Dominic Scaglioni Xuechun Wang Ju Qu Marko Nikolic Marco Montagner Gabriel L. Galea Hans Clevers Monica Giomo Paolo De Coppi Nicola Elvassore |
| author_facet | Anna Urciuolo Giovanni Giuseppe Giobbe Yixiao Dong Federica Michielin Luca Brandolino Michael Magnussen Onelia Gagliano Giulia Selmin Valentina Scattolini Paolo Raffa Paola Caccin Soichi Shibuya Dominic Scaglioni Xuechun Wang Ju Qu Marko Nikolic Marco Montagner Gabriel L. Galea Hans Clevers Monica Giomo Paolo De Coppi Nicola Elvassore |
| author_sort | Anna Urciuolo |
| collection | DOAJ |
| description | Abstract Three-dimensional hydrogel-based organ-like cultures can be applied to study development, regeneration, and disease in vitro. However, the control of engineered hydrogel composition, mechanical properties and geometrical constraints tends to be restricted to the initial time of fabrication. Modulation of hydrogel characteristics over time and according to culture evolution is often not possible. Here, we overcome these limitations by developing a hydrogel-in-hydrogel live bioprinting approach that enables the dynamic fabrication of instructive hydrogel elements within pre-existing hydrogel-based organ-like cultures. This can be achieved by crosslinking photosensitive hydrogels via two-photon absorption at any time during culture. We show that instructive hydrogels guide neural axon directionality in growing organotypic spinal cords, and that hydrogel geometry and mechanical properties control differential cell migration in developing cancer organoids. Finally, we show that hydrogel constraints promote cell polarity in liver organoids, guide small intestinal organoid morphogenesis and control lung tip bifurcation according to the hydrogel composition and shape. |
| first_indexed | 2024-03-13T07:22:25Z |
| format | Article |
| id | doaj.art-8d949ed909e143ba8263b25ad3233dc1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T07:22:25Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-8d949ed909e143ba8263b25ad3233dc12023-06-04T11:33:36ZengNature PortfolioNature Communications2041-17232023-05-0114111410.1038/s41467-023-37953-4Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic culturesAnna Urciuolo0Giovanni Giuseppe Giobbe1Yixiao Dong2Federica Michielin3Luca Brandolino4Michael Magnussen5Onelia Gagliano6Giulia Selmin7Valentina Scattolini8Paolo Raffa9Paola Caccin10Soichi Shibuya11Dominic Scaglioni12Xuechun Wang13Ju Qu14Marko Nikolic15Marco Montagner16Gabriel L. Galea17Hans Clevers18Monica Giomo19Paolo De Coppi20Nicola Elvassore21Dept. of Molecular Medicine, University of PadovaGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech UniversityGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonDept. of Industrial Engineering, University of PadovaGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonDept. of Industrial Engineering, University of PadovaGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonIstituto di Ricerca Pediatrica, Città della SperanzaIstituto di Ricerca Pediatrica, Città della SperanzaDept. of Biomedical Science, University of PadovaGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech UniversityGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonDept. of Molecular Medicine, University of PadovaGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonHubrecht Institute, KNAW and University Medical CenterDept. of Industrial Engineering, University of PadovaGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonGOSICH Zayed Centre for Research into Rare Disease in Children, University College LondonAbstract Three-dimensional hydrogel-based organ-like cultures can be applied to study development, regeneration, and disease in vitro. However, the control of engineered hydrogel composition, mechanical properties and geometrical constraints tends to be restricted to the initial time of fabrication. Modulation of hydrogel characteristics over time and according to culture evolution is often not possible. Here, we overcome these limitations by developing a hydrogel-in-hydrogel live bioprinting approach that enables the dynamic fabrication of instructive hydrogel elements within pre-existing hydrogel-based organ-like cultures. This can be achieved by crosslinking photosensitive hydrogels via two-photon absorption at any time during culture. We show that instructive hydrogels guide neural axon directionality in growing organotypic spinal cords, and that hydrogel geometry and mechanical properties control differential cell migration in developing cancer organoids. Finally, we show that hydrogel constraints promote cell polarity in liver organoids, guide small intestinal organoid morphogenesis and control lung tip bifurcation according to the hydrogel composition and shape.https://doi.org/10.1038/s41467-023-37953-4 |
| spellingShingle | Anna Urciuolo Giovanni Giuseppe Giobbe Yixiao Dong Federica Michielin Luca Brandolino Michael Magnussen Onelia Gagliano Giulia Selmin Valentina Scattolini Paolo Raffa Paola Caccin Soichi Shibuya Dominic Scaglioni Xuechun Wang Ju Qu Marko Nikolic Marco Montagner Gabriel L. Galea Hans Clevers Monica Giomo Paolo De Coppi Nicola Elvassore Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures Nature Communications |
| title | Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures |
| title_full | Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures |
| title_fullStr | Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures |
| title_full_unstemmed | Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures |
| title_short | Hydrogel-in-hydrogel live bioprinting for guidance and control of organoids and organotypic cultures |
| title_sort | hydrogel in hydrogel live bioprinting for guidance and control of organoids and organotypic cultures |
| url | https://doi.org/10.1038/s41467-023-37953-4 |
| work_keys_str_mv | AT annaurciuolo hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT giovannigiuseppegiobbe hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT yixiaodong hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT federicamichielin hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT lucabrandolino hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT michaelmagnussen hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT oneliagagliano hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT giuliaselmin hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT valentinascattolini hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT paoloraffa hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT paolacaccin hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT soichishibuya hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT dominicscaglioni hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT xuechunwang hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT juqu hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT markonikolic hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT marcomontagner hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT gabriellgalea hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT hansclevers hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT monicagiomo hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT paolodecoppi hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures AT nicolaelvassore hydrogelinhydrogellivebioprintingforguidanceandcontroloforganoidsandorganotypiccultures |