Date of Award
Master of Science (MS)
Biomedical and Chemical Engineering and Sciences
Kenia P. Nunes
Venkat Keshav Chivukula
Astrocytes are crucial in preserving the structural and functional integrity of the central nervous system (CNS). They participate in several physiological processes, such as the uptake of neurotransmitters, control of extracellular ion concentration, and preservation of the blood-brain barrier. Recent research has raised the possibility that astrocytes are also involved in the onset and development of Alzheimer's disease (AD). While the precise mechanisms underlying the development and progression of AD are not fully understood, recent research has suggested that age-related changes in the brain extracellular matrix (ECM) properties may play a critical role in the progression of the disease. Investigating the impact of brain ECM properties on astrocyte cell response can help unravel the possible impact of the ECM on AD. In this study, in vitro xeno-free biomimetic hydrogel-based brain ECM models were employed to investigate the impact of ECM composition and stiffness on astrocyte cell response. Variable ratios of human collagen type I and thiolated hyaluronic acid (HA) crosslinked with polyethylene glycol diacrylate were used to create the xeno-free ECM models. Results demonstrated that modifying the composition of the ECM produced hydrogels with varied stiffness that were comparable to the stiffness of the native brain ECM. Hydrogels rich in collagen showed better stability and increased swelling. Hydrogels with lower HA composition showed better cell spreading and metabolic activity. In addition, softer hydrogels showed greater cell spreading, elevated GFAP expression, and decreased ALDH1L1 expression, suggesting that matrix stiffness influences astrocyte activation. This study proposes a basic model of the brain ECM to study the synergistic effects of ECM composition and stiffness on astrocytes. Future studies can focus on building on this work by incorporating additional matrix proteins to identify key ECM biomarkers and develop new strategies to overcome the impact of ECM changes on the onset and progression of neurodegenerative illnesses such as AD.
Saleh, Bayan, "Xeno-Free Biomimetic ECM Model for Investigation of Matrix Properties on Astrocyte Cell Response" (2023). Theses and Dissertations. 1256.
Available for download on Monday, May 06, 2024