Brain-Derived Extracellular Matrix (B-ECM)-Based Aligned Electrospun Fibers for Sciatic Nerve Regeneration

Abstract

Nerve injuries pose numerous challenges and adversely affect the quality-of-life (QOL) of patients. Artificial nerve guidance conduits (aNGCs) are fabricated using natural and synthetic polymers alongside bioactive cues. The objective of this study is to simultaneously leverage biophysical and biochemical cues to develop aNGCs. The study fabricates core/shell aligned electrospun fibers using polycaprolactone (PCL) and brain-derived extracellular matrix/gelatin (B-ECM/Gel) as core and shell components, respectively, and then integrates them with PCL/Gel-based tubular scaffolds to fabricate aNGCs. H&E staining and DNA quantification of B-ECM manifest successful removal of cell nuclei alongside preserved biochemical cues (e.g., glycosaminoglycans, proteins, etc.), which influenced the migration and neurite outgrowth of Schwann cells and Pheochromocytoma (PC12) cells in a dose-dependent manner both in the solubilized form and as aligned fibers in vitro. PCL/Gel fibers (layer thickness = 400–500 µm) enhanced the transport of nutrients, while tubular scaffolds suppressed the accumulation of inflammatory cells at the scaffold-tissue interface. In vivo evaluation of aNGCs in a rat sciatic nerve defect model (length = 1 cm) exhibit host cell infiltration aligned along the alignment direction of fibers. Nerve regeneration is higher in aNGCs containing B-ECM. B-ECM-based aligned fibers may have broad implications for neural engineering and potentially other bio-related disciplines.