Coral skeleton regulates astrocytic reactivity and scar oormation in injured nervous tissue in vitro

Traumatic brain injury (TBI) results in massive cell death and scar-tissue formation, disabling self-recovery. Reducing scar formation by grafting scaffolds may be a promising strategy to evoke recovery. Our previous studies demonstrated positive effects of coral-skeleton on astrocytic survival and activation in-vitro. This study aimed to develop an in-vitro injury model, where the scar formation-related processes could be evaluated. In this model, the injury, treatment and astrocytic reaction were presented as follows: 1. Injured tissue: 0.7X0.7X1mm hippocampal tissue-slices, injured at all edges. 2. Scaffold implantation: Cultivation of injured slices on coral-skeleton matrices. 3. Scar formation regulation by scaffold manipulation: Two scaffold surfaces were designed: (a)intact skeleton piece (ISP): porous, microrough; (b)grained skeleton (GS): nonporous, macrorough. 4. Astrocytic reactivity: acquisition of spiky shape and overexpression of GFAP in astrocytes within the slice and among astrocytes migrating from it. 5. Scar formation: assembly of these astrocytes into large dense structures. The results showed that on GS, the tissue exhibited a scar-like organization at its periphery and astrocytes migrating out of the slice dispersed evenly. On ISP, there was no scar-like organization within the slice, nor among migrating cells. On GS, but not on ISP, the morphology of the migrating cells changed gradually, from spiky towards flat (near, culture’s edge respectively). In addition, a GFAP expression gradient was detected among migrating astrocytes, from low to high levels near and far from the slice (respectively). Total GFAP expression levels were increased on ISP, compared to GS. Altogether, these results indicate that astrocytic reactivity and scar formation can be regulated by implanting coralline scaffolds of distinct surface-architectures to TBI wounds. Such regulation may gain control over damage repair following TBI.