Macro/microstructured quercetin-loaded poly(lactide-co-glycolide) scaffolds for neural tissue engineering

Modern brain tissue engineering strategies can exploit the antioxidant and anti-inflammatory properties of quercetin (Que) by encapsulating it in a biodegradable polymer to develop bioactive scaffolds. The aim of this research was to develop Que-loaded poly(lactide- co -glycolide) (PLGA) scaffolds structured at different scales using either solution-extrusion additive manufacturing (AM) or electrospinning. The 3D scaffolds produced by AM had a macroporous structure and micropores distributed throughout the fiber cross-section. The electrospun meshes were composed of microfibers with a diameter of around 2 μm that could be deposited on top of 3D scaffolds to form a dual-scale structure. Que was successfully loaded into the two types of PLGA systems with high encapsulation efficiency (>90%). In vitro release of Que was only detected in the case of electrospun meshes but not for 3D scaffolds and dual-scale constructs due to their lower specific surface area and the partial degradation of the flavonoid in phosphate buffer saline (PBS) at 37 °C. Que loading had a significant impact on both the glass transition temperature of the polymer in 3D scaffolds and the tensile properties of electrospun meshes. Flavonoid loading or device morphology did not affect the in vitro degradation of the polymer, whose molecular weight was reduced by half in 8 weeks in PBS at 37 °C. The meshes had similar radical scavenging activity to free Que, while the antioxidant activity of the dual-scale scaffolds was in-between those of 3D scaffolds and meshes. Cell culture experiments on microglia cells confirmed that Que loaded on PLGA meshes maintains its anti-inflammatory activity. The obtained results demonstrate the potential of the developed devices as surgical bioactive scaffolds for treating brain damage.