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Abstract
The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant
component of the brain due to its instructive role in the compartmentalization of
functional microdomains in every brain structure. The composition, quantity and structure
of ECM changes dramatically during the development of an organism greatly contributing
to the remarkably sophisticated architecture and function of the brain. Since fetal
brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues
promoting neural growth and differentiation, highly desired in regenerative medicine.
Thus, we studied the effect of brain-derived fetal and adult ECM complemented with
matricellular proteins on cortical neurons using in vitro 3D bioengineered model of
cortical brain tissue. The tested parameters included neuronal network density, cell
viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM
as well as matricellular proteins significantly improved neural network formation
as compared to single component, collagen I matrix. Additionally, the brain ECM improved
cell viability and lowered glutamate release. The fetal brain ECM induced superior
neural network formation, calcium signaling and spontaneous spiking activity over
adult brain ECM. This study highlights the difference in the neuroinductive properties
of fetal and adult brain ECM and suggests that delineating the basis for this divergence
may have implications for regenerative medicine.