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Increasing Durability of Dissociated Neural Cell Cultures Using Biologically Active Coralline Matrix

Cultures of dissociated hippocampal neuronal and glial cells are a valuable experimental model for studying neural growth and function by providing high ...

Ariel University

Following traumatic brain injury, there is no restoration of the lost nervous tissue, mainly due to the formation of a scar. One promising strategy to overcome this hurdle is grafting scaffolds that can disturb the scar blockade, enabling cell invasion into the wound. The aragonite skeleton of corals is useful scaffolds for testing this strategy, being supportive for neural cells in culture. The purpose of this work was to check if a contact between a coralline scaffold and an injured nervous tissue affects scar formation and if this effect can be regulated by engineering the scaffold's surface topology. To address that, hippocampal slices were cultivated on a coral skeleton having two distinct surface shapes: (1) intact skeleton pieces (ISP): porous, microrough surface; (2) grained skeleton (GS): nonporous, macrorough surface. On ISP, slices deformed by engulfing the scaffold's outer surface without penetrating the pores, yet, they preserved their coherence. By contrast, on GS slices were flat, but broken into interconnected small segments of tissue. In addition, whereas on ISP astrocytes were significantly more active and diffusely distributed, on GS reactive astrocytes tightened into a single <90 μm wide scar-like stripe at the slice's periphery. Hence, by grafting coralline scaffolds of predesigned surface roughness and porosity into brain wounds, control over scar tissue formation can be gained, providing an opportunity for cell migration and damage repair. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2295-2306, 2018.

Modulation of scar tissue formation in injured nervous tissue cultivated on surface-engineered coralline scaffolds.

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. We have 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 μm height 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 astrogliosis-derived regeneration in TBI wounds, and as a result improve the capacity to repair brain damage.

Article	Year
Modulation of scar tissue formation in injured nervous tissue cultivated on surface-engineered coralline scaffolds. Journal of biomedical materials research. Part B, Applied biomaterials\| PubMed ID: 29098785	2018
Gliosis of astrocytes cultivated on coral skeleton is regulated by the matrix surface topography. Biomedical materials (Bristol, England)\| PubMed ID: 30840929	2019

Roni Mina Hendler

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