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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Journal of Functional Biomaterials |
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| Online Access: | https://www.mdpi.com/2079-4983/14/5/256 |
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| author | Bayan M. Saleh Ayda Pourmostafa Nashaita Y. Patrawalla Vipuil Kishore |
| author_facet | Bayan M. Saleh Ayda Pourmostafa Nashaita Y. Patrawalla Vipuil Kishore |
| author_sort | Bayan M. Saleh |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T03:36:11Z |
| format | Article |
| id | doaj.art-19b377420db446fe807b7c0323d22eca |
| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-03-11T03:36:11Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj.art-19b377420db446fe807b7c0323d22eca2023-11-18T01:56:47ZengMDPI AGJournal of Functional Biomaterials2079-49832023-05-0114525610.3390/jfb14050256Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell ResponseBayan M. Saleh0Ayda Pourmostafa1Nashaita Y. Patrawalla2Vipuil Kishore3Department of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, FL 32901, USADepartment of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, FL 32901, USADepartment of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, FL 32901, USADepartment of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, Melbourne, FL 32901, USAAstrocytes, 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.https://www.mdpi.com/2079-4983/14/5/256extracellular matrixhyaluronic acidcollagenhydrogelastrocytesAlzheimer’s disease |
| spellingShingle | Bayan M. Saleh Ayda Pourmostafa Nashaita Y. Patrawalla Vipuil Kishore Xeno-Free Biomimetic ECM Model for Investigation of Matrix Composition and Stiffness on Astrocyte Cell Response Journal of Functional Biomaterials extracellular matrix hyaluronic acid collagen hydrogel astrocytes Alzheimer’s disease |
| 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 | extracellular matrix hyaluronic acid collagen hydrogel astrocytes Alzheimer’s disease |
| url | https://www.mdpi.com/2079-4983/14/5/256 |
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