Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocity

Xenogeneic tumour origin and batch-to-batch variability of Engelbreth-Holm-Swarm sarcoma tumour cell-derived hydrogels (Matrigel, Cultrex) limit the biomedical application of organoids in tissue engineering. The gelatin-methacryloyl (GelMA) hydrogels represent a defined, tunable, and GMP-friendly al...

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Main Authors: Lenie Vanhove, Thomas Van Gansbeke, Bert Devriendt, Ruben Van der Meeren, Ruslan I. Dmitriev, Irina A. Okkelman
Format: Article
Language:English
Published: SAGE Publishing 2025-06-01
Series:Journal of Tissue Engineering
Online Access:https://doi.org/10.1177/20417314251345000
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author Lenie Vanhove
Thomas Van Gansbeke
Bert Devriendt
Ruben Van der Meeren
Ruslan I. Dmitriev
Irina A. Okkelman
author_facet Lenie Vanhove
Thomas Van Gansbeke
Bert Devriendt
Ruben Van der Meeren
Ruslan I. Dmitriev
Irina A. Okkelman
author_sort Lenie Vanhove
collection DOAJ
description Xenogeneic tumour origin and batch-to-batch variability of Engelbreth-Holm-Swarm sarcoma tumour cell-derived hydrogels (Matrigel, Cultrex) limit the biomedical application of organoids in tissue engineering. The gelatin-methacryloyl (GelMA) hydrogels represent a defined, tunable, and GMP-friendly alternative, but they are rarely studied as alternative to Matrigel. Here, we studied effects of mechanical properties of GelMA and addition of laminin-111 on encapsulation and growth of small intestinal organoids. GelMA-embedded organoids displayed polarity reversion, resulting in apical-out and apical-basal phenotypes, independent from the matrix stiffness. Addition of laminin-111 softened hydrogels and also resulted in a partial restoration of the basal-out phenotype. Interestingly, despite the incomplete polarity restoration, GelMA-organoids still showed minor growth. GelMA stiffness and concentration influenced the transition from 3D to 2D organoid cultures. Collectively, our study confirms that tuning of GelMA mechanical properties alone cannot recapitulate the basal membrane matrix. However, controlled polarity reversion offers a tool for engineering organoids and enabling apical membrane access.
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institution Kabale University
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publisher SAGE Publishing
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spelling doaj-art-cbff20f867164e64a37a5ca38f50d1f92025-08-20T03:25:57ZengSAGE PublishingJournal of Tissue Engineering2041-73142025-06-011610.1177/20417314251345000Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocityLenie Vanhove0Thomas Van Gansbeke1Bert Devriendt2Ruben Van der Meeren3Ruslan I. Dmitriev4Irina A. Okkelman5Mitochondrial Investigations Laboratory, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, BelgiumRousselot BV, Darling Ingredients, Ghent, BelgiumLaboratory of Immunology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, BelgiumRousselot BV, Darling Ingredients, Ghent, BelgiumTissue Engineering and Biomaterials Group, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, BelgiumTissue Engineering and Biomaterials Group, Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, BelgiumXenogeneic tumour origin and batch-to-batch variability of Engelbreth-Holm-Swarm sarcoma tumour cell-derived hydrogels (Matrigel, Cultrex) limit the biomedical application of organoids in tissue engineering. The gelatin-methacryloyl (GelMA) hydrogels represent a defined, tunable, and GMP-friendly alternative, but they are rarely studied as alternative to Matrigel. Here, we studied effects of mechanical properties of GelMA and addition of laminin-111 on encapsulation and growth of small intestinal organoids. GelMA-embedded organoids displayed polarity reversion, resulting in apical-out and apical-basal phenotypes, independent from the matrix stiffness. Addition of laminin-111 softened hydrogels and also resulted in a partial restoration of the basal-out phenotype. Interestingly, despite the incomplete polarity restoration, GelMA-organoids still showed minor growth. GelMA stiffness and concentration influenced the transition from 3D to 2D organoid cultures. Collectively, our study confirms that tuning of GelMA mechanical properties alone cannot recapitulate the basal membrane matrix. However, controlled polarity reversion offers a tool for engineering organoids and enabling apical membrane access.https://doi.org/10.1177/20417314251345000
spellingShingle Lenie Vanhove
Thomas Van Gansbeke
Bert Devriendt
Ruben Van der Meeren
Ruslan I. Dmitriev
Irina A. Okkelman
Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocity
Journal of Tissue Engineering
title Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocity
title_full Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocity
title_fullStr Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocity
title_full_unstemmed Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocity
title_short Lack of biochemical signalling in GelMA leads to polarity reversion in intestinal organoids independent from mechanoreciprocity
title_sort lack of biochemical signalling in gelma leads to polarity reversion in intestinal organoids independent from mechanoreciprocity
url https://doi.org/10.1177/20417314251345000
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