Gliosis of astrocytes cultivated on coral skeleton is regulated by the matrix surface topography

摘要

Astrogilosis is the response of astrocytes to brain trauma which manifest opposite roles on brain injury repair. On the one hand, astrocytes undergoing astrogliosis inhibit tissue regeneration by forming scar tissue, but, on the other hand, they enhance damage repair through secretion of neuro-protecting and neurotrophic factors. Therefore, identifying means that regulate astrogliosis can provide a control over progression and repair of brain damage.Wehave previously shown that the calcium carbonate skeleton of corals upregulates two manifestations of astrogliosis in astrocytes in culture-expression of the Glial Fibrillay Acidic Protein (GFAP), and shape conversion from non-spiky to reactive spiky cell morphology. Here, we investigated if the surface topography of the coralline skeleton plays a role in GFAP expression and the morphogenesis of reactive astrocytes. To address that, we utilized the non-porous exoskeleton of the coral Trachyphyllia geoffroyi, having three topographies of distinct heights on its surface: rough surface (made of<30 μmheight bumps), protrusions (50-250 μm) and ridges (>250 μm).We observed that astrocytes reacted similarly to all three structures in terms of adhesion, acquisition of a spiky morphology and organization in networks. By contrast, the extent by which these cells expressed GFAP was structure-dependent. The expression was 2-fold higher on protrusions and ridges than on the rough surface and acquired. Accordingly, the distribution pattern of the GFAP overexpressing astrocytes followed that of the protrusions and ridges. Hence, fabricating coralline scaffolds with designed flatness/protrusions/ridges ratios can serve to control astrogliosisderived regeneration in TBI wounds, and as a result improve the capacity to repair brain damage.