Photocrosslinkable liver extracellular matrix hydrogels for the generation of 3D liver microenvironment models

Abstract Liver extracellular matrix (ECM)-based hydrogels have gained considerable interest as biomimetic 3D cell culture environments to investigate the mechanisms of liver pathology, metabolism, and toxicity. The preparation of current liver ECM hydrogels, however, is based on time-consuming therm...

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Autores principales: Akhilandeshwari Ravichandran, Berline Murekatete, Denise Moedder, Christoph Meinert, Laura J. Bray
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:491fa025fe4b4c02beea3ed0e7195ee52021-12-02T16:31:51ZPhotocrosslinkable liver extracellular matrix hydrogels for the generation of 3D liver microenvironment models10.1038/s41598-021-94990-z2045-2322https://doaj.org/article/491fa025fe4b4c02beea3ed0e7195ee52021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94990-zhttps://doaj.org/toc/2045-2322Abstract Liver extracellular matrix (ECM)-based hydrogels have gained considerable interest as biomimetic 3D cell culture environments to investigate the mechanisms of liver pathology, metabolism, and toxicity. The preparation of current liver ECM hydrogels, however, is based on time-consuming thermal gelation and limits the control of mechanical properties. In this study, we used detergent-based protocols to produce decellularized porcine liver ECM, which in turn were solubilized and functionalized with methacrylic anhydride to generate photocrosslinkable methacrylated liver ECM (LivMA) hydrogels. Firstly, we explored the efficacy of two protocols to decellularize porcine liver tissue using varying combinations of commonly used chemical agents such as Triton X-100, Sodium Dodecyl Sulphate (SDS) and Ammonium hydroxide. Then, we demonstrated successful formation of stable, reproducible LivMA hydrogels from both the protocols by photocrosslinking. The LivMA hydrogels obtained from the two decellularization protocols showed distinct mechanical properties. The compressive modulus of the hydrogels was directly dependent on the hydrogel concentration, thereby demonstrating the tuneability of mechanical properties of these hydrogels. Immortalized Human Hepatocytes cells were encapsulated in the LivMA hydrogels and cytocompatibility of the hydrogels was demonstrated after one week of culture. In summary, the LivMA hydrogel system provides a simple, photocrosslinkable platform, which can potentially be used to simulate healthy versus damaged liver for liver disease research, drug studies and cancer metastasis modelling.Akhilandeshwari RavichandranBerline MurekateteDenise MoedderChristoph MeinertLaura J. BrayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Akhilandeshwari Ravichandran
Berline Murekatete
Denise Moedder
Christoph Meinert
Laura J. Bray
Photocrosslinkable liver extracellular matrix hydrogels for the generation of 3D liver microenvironment models
description Abstract Liver extracellular matrix (ECM)-based hydrogels have gained considerable interest as biomimetic 3D cell culture environments to investigate the mechanisms of liver pathology, metabolism, and toxicity. The preparation of current liver ECM hydrogels, however, is based on time-consuming thermal gelation and limits the control of mechanical properties. In this study, we used detergent-based protocols to produce decellularized porcine liver ECM, which in turn were solubilized and functionalized with methacrylic anhydride to generate photocrosslinkable methacrylated liver ECM (LivMA) hydrogels. Firstly, we explored the efficacy of two protocols to decellularize porcine liver tissue using varying combinations of commonly used chemical agents such as Triton X-100, Sodium Dodecyl Sulphate (SDS) and Ammonium hydroxide. Then, we demonstrated successful formation of stable, reproducible LivMA hydrogels from both the protocols by photocrosslinking. The LivMA hydrogels obtained from the two decellularization protocols showed distinct mechanical properties. The compressive modulus of the hydrogels was directly dependent on the hydrogel concentration, thereby demonstrating the tuneability of mechanical properties of these hydrogels. Immortalized Human Hepatocytes cells were encapsulated in the LivMA hydrogels and cytocompatibility of the hydrogels was demonstrated after one week of culture. In summary, the LivMA hydrogel system provides a simple, photocrosslinkable platform, which can potentially be used to simulate healthy versus damaged liver for liver disease research, drug studies and cancer metastasis modelling.
format article
author Akhilandeshwari Ravichandran
Berline Murekatete
Denise Moedder
Christoph Meinert
Laura J. Bray
author_facet Akhilandeshwari Ravichandran
Berline Murekatete
Denise Moedder
Christoph Meinert
Laura J. Bray
author_sort Akhilandeshwari Ravichandran
title Photocrosslinkable liver extracellular matrix hydrogels for the generation of 3D liver microenvironment models
title_short Photocrosslinkable liver extracellular matrix hydrogels for the generation of 3D liver microenvironment models
title_full Photocrosslinkable liver extracellular matrix hydrogels for the generation of 3D liver microenvironment models
title_fullStr Photocrosslinkable liver extracellular matrix hydrogels for the generation of 3D liver microenvironment models
title_full_unstemmed Photocrosslinkable liver extracellular matrix hydrogels for the generation of 3D liver microenvironment models
title_sort photocrosslinkable liver extracellular matrix hydrogels for the generation of 3d liver microenvironment models
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/491fa025fe4b4c02beea3ed0e7195ee5
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AT denisemoedder photocrosslinkableliverextracellularmatrixhydrogelsforthegenerationof3dlivermicroenvironmentmodels
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