Implantation of functionalized thermally gelling xyloglucan hydrogel within the brain: associated neurite infiltration and inflammatory response

Abstract

To develop neural tissue engineering strategies that are useful for repairing damaged neural pathways in the central nervous system, it is essential to control and optimise neurone and neurite interactions with functional scaffolds. In this study, the suitability of thermally gelling xyloglucan hydrogels, along with xyloglucan-graft-poly-d-lysine (PDL) hydrogels, was assessed through their implantation within the caudate putamen of adult rats. The ability of the hydrogel scaffolds to encourage the infiltration of axons in a controlled manner was investigated, as was the inflammatory response associated with the implantation. The microglia reaction was the same for unmodified xyloglucan and the xyloglucan-graft-PDL scaffolds, peaking after 3 days before decreasing back to homeostatic levels after ∼28 days. Penetration of the microglia into the scaffold was not observed, with these cells accumulating at the scaffold-tissue interface. For astrocytes, the other type of glial cell with migratory capacity, the peak activation occurred between 14 and 21 days. This reaction subsided more rapidly for the unmodified scaffold compared to the xyloglucan-graft-PDL scaffolds, which remained elevated 21-28 days before returning to homeostatic levels within 60 days. Most noteworthy was the discovery of increased infiltration levels for astrocytes and neurites with higher concentrations of grafted PDL. The timing of the astrocyte migration coincided with neurite infiltration within the scaffolds, suggesting that astrocytes may have facilitated this infiltration, possibly due to the secretion of laminin.