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Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response

Astrocytes, highly specialized glial cells, play a critical role in neuronal function. Variations in brain extracellular matrix (ECM) during development and disease can significantly alter astrocyte cell function. Age-related changes in ECM properties have been linked to neurodegenerative diseases s...

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Autores principales: Saleh, Bayan M., Pourmostafa, Ayda, Patrawalla, Nashaita Y., Kishore, Vipuil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218816/
https://www.ncbi.nlm.nih.gov/pubmed/37233366
http://dx.doi.org/10.3390/jfb14050256
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author Saleh, Bayan M.
Pourmostafa, Ayda
Patrawalla, Nashaita Y.
Kishore, Vipuil
author_facet Saleh, Bayan M.
Pourmostafa, Ayda
Patrawalla, Nashaita Y.
Kishore, Vipuil
author_sort Saleh, Bayan M.
collection PubMed
description Astrocytes, highly specialized glial cells, play a critical role in neuronal function. Variations in brain extracellular matrix (ECM) during development and disease can significantly alter astrocyte cell function. Age-related changes in ECM properties have been linked to neurodegenerative diseases such as Alzheimer’s disease. The goal of this study was to develop hydrogel-based biomimetic ECM models with varying stiffness and evaluate the effects of ECM composition and stiffness on astrocyte cell response. Xeno-free ECM models were synthesized by combining varying ratios of human collagen and thiolated hyaluronic acid (HA) crosslinked with polyethylene glycol diacrylate. Results showed that modulating ECM composition yielded hydrogels with varying stiffnesses that match the stiffness of the native brain ECM. Collagen-rich hydrogels swell more and exhibit greater stability. Higher metabolic activity and greater cell spreading was observed in hydrogels with lower HA. Soft hydrogels trigger astrocyte activation indicated by greater cell spreading, high GFAP expression and low ALDH1L1 expression. This work presents a baseline ECM model to investigate the synergistic effects of ECM composition and stiffness on astrocytes, which could be further developed to identify key ECM biomarkers and formulate new therapies to alleviate the impact of ECM changes on the onset and progression of neurodegenerative diseases.
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spelling pubmed-102188162023-05-27 Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response Saleh, Bayan M. Pourmostafa, Ayda Patrawalla, Nashaita Y. Kishore, Vipuil J Funct Biomater Article Astrocytes, highly specialized glial cells, play a critical role in neuronal function. Variations in brain extracellular matrix (ECM) during development and disease can significantly alter astrocyte cell function. Age-related changes in ECM properties have been linked to neurodegenerative diseases such as Alzheimer’s disease. The goal of this study was to develop hydrogel-based biomimetic ECM models with varying stiffness and evaluate the effects of ECM composition and stiffness on astrocyte cell response. Xeno-free ECM models were synthesized by combining varying ratios of human collagen and thiolated hyaluronic acid (HA) crosslinked with polyethylene glycol diacrylate. Results showed that modulating ECM composition yielded hydrogels with varying stiffnesses that match the stiffness of the native brain ECM. Collagen-rich hydrogels swell more and exhibit greater stability. Higher metabolic activity and greater cell spreading was observed in hydrogels with lower HA. Soft hydrogels trigger astrocyte activation indicated by greater cell spreading, high GFAP expression and low ALDH1L1 expression. This work presents a baseline ECM model to investigate the synergistic effects of ECM composition and stiffness on astrocytes, which could be further developed to identify key ECM biomarkers and formulate new therapies to alleviate the impact of ECM changes on the onset and progression of neurodegenerative diseases. MDPI 2023-05-05 /pmc/articles/PMC10218816/ /pubmed/37233366 http://dx.doi.org/10.3390/jfb14050256 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Saleh, Bayan M.
Pourmostafa, Ayda
Patrawalla, Nashaita Y.
Kishore, Vipuil
Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response
title Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response
title_full Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response
title_fullStr Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response
title_full_unstemmed Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response
title_short Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response
title_sort xeno-free biomimetic ecm model for investigation of matrix composition and stiffness on astrocyte cell response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10218816/
https://www.ncbi.nlm.nih.gov/pubmed/37233366
http://dx.doi.org/10.3390/jfb14050256
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