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.

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.

Inflammatory and immunogenic response to foreign bodies presents a challenge in the use of biomaterials as implants for tissue restoration. Therefore, there is a need to understand the interactions between such implants and the blood. One such material, currently in clinical use for bone replacement in humans, is the skeleton of corals, in the form of crystalline aragonite. This biomaterial has been shown to impart a protective and supportive influence on several types of cells ex vivo. The carbonate skeleton activates secretion in phagocytes in vitro, however its effects on these cells in the blood, and on the process of phagocytosis itself, remain unknown. Using 1–500 μm particles of coral skeleton, we show that these particles bind blood proteins and alter the leukocyte population, reducing the proportion of granulocytes by more than 3‐fold with no effect on the proportion of monocytes. In addition, the presence of coral skeleton in the blood causes a reduction in phagocytosis. Specifically, we observed a decrease in the percentage of phagocytic cells by 27 % in the granulocytes and by 73 % in monocyte family, as well as a 41.6 % reduction in the MFI of granulocytes, but with no such effect on monocytes. Taken together, the results suggest that the coral skeleton biomaterial may act as a strong, promotive scaffold for tissue regeneration due to its ability to reduce its rejection by inflammatory reactions such as phagocytosis.

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Biomaterials, especially when coated with adhesive polymers, are a key tool for restorative medicine, being biocompatible and supportive for cell adherence, growth, and function. Aragonite skeletons of corals are biomaterials that support survival and growth of a range of cell types, including neurons and glia. However, it is not known if this scaffold affects neural cell migration or elongation of neuronal and astrocytic processes, prerequisites for initiating repair of damage in the nervous system. To address this, hippocampal cells were aggregated into neurospheres and cultivated on aragonite skeleton of the coral Trachyphyllia geoffroyi (Coral Skeleton (CS)), on naturally occurring aragonite (Geological Aragonite (GA)), and on glass, all pre-coated with the oligomer poly-D-lysine (PDL). The two aragonite matrices promoted equally strong cell migration (4.8 and 4.3-fold above glass-PDL, respectively) and axonal sprouting (1.96 and 1.95-fold above glass-PDL, respectively). However, CS-PDL had a stronger effect than GA-PDL on the promotion of astrocytic processes elongation (1.7 vs. 1.2-fold above glass-PDL, respectively) and expression of the glial fibrillary acidic protein (3.8 vs. and 1.8-fold above glass-PDL, respectively). These differences are likely to emerge from a reaction of astrocytes to the degree of roughness of the surface of the scaffold, which is higher on CS than on GA. Hence, CS-PDL and GA-PDL are scaffolds of strong capacity to derive neural cell movements and growth required for regeneration, while controlling the extent of astrocytic involvement. As such, implants of PDL-aragonites have significant potential as tools for damage repair and the reduction of scar formation in the brain following trauma or disease.

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Biomaterials, especially when coated with adhesive polymers, are a key tool for restorative medicine, being biocompatible and supportive for cell adherence, growth, and function. Aragonite skeletons of corals are biomaterials that support survival and growth of a range of cell types, including neurons and glia. www.videleaf.com However, it is not known if this scaffold affects neural cell migration or elongation of neuronal and astrocytic processes, prerequisites for initiating repair of damage in the nervous system. To address this, hippocampal cells were aggregated into neurospheres and cultivated on aragonite skeleton of the coral Trachyphyllia geoffroyi (Coral Skeleton (CS)), on naturally occurring aragonite (Geological Aragonite (GA)), and on glass, all pre-coated with the oligomer poly-D-lysine (PDL). The two aragonite matrices promoted equally strong cell migration (4.8 and 4.3-fold above glass-PDL, respectively) and axonal sprouting (1.96 and 1.95-fold above glass-PDL, respectively). However, CS-PDL had a stronger effect than GA-PDL on the promotion of astrocytic processes elongation (1.7 vs. 1.2-fold above glass-PDL, respectively) and expression of the glial fibrillary acidic protein (3.8 vs. and 1.8-fold above glass-PDL, respectively). These differences are likely to emerge from a reaction of astrocytes to the degree of roughness of the surface of the scaffold, which is higher on CS than on GA. Hence, CS-PDL and GA-PDL are scaffolds of strong capacity to derive neural cell movements and growth required for regeneration, while controlling the extent of astrocytic involvement. As such, implants of PDL-aragonites have significant potential as tools for damage repair and the reduction of scar formation in the brain following trauma or disease.