Chlorogenic acid releasing microspheres enhanced electrospun conduits to promote peripheral nerve regeneration

Chlorogenic acid (CGA) has been confirmed as a polyphenol, and existing research has suggested the high bioactivity of CGA for therapeutic effects on a wide variety of diseases. Despite the existing reports of anti-inflammatory, antioxidant, and neuroprotective effects of CGA, the role and mechanism of CGA in facilitating the regeneration of peripheral nerve defects have been rarely investigated. Herein, a biodegradable polycaprolactone (PCL) conduit with embedded CGA-releasing GelMA microspheres (CGM/PCL) was successfully prepared and used for repairing a rate model with sciatic nerve defects. CGM and CGM/PCL conduits displayed high in vitro biocompatibility and can support the growth of cells for nerve regeneration. Furthermore, CGM/PCL conduits displayed high performance which is close to that of autologous nerve grafts in promoting in vivo PNI regeneration, compared with PCL conduits. The sciatic nerve functional index analysis, electrophysiological examination, and immunological analysis performed to evaluate the functional recovery of the injurious sciatic nerve of rats have indeed proved the favorable effects of CGM/PCL conduits. The result of this study not only aimed to explore CGA's contribution to nerve regeneration but also provided a new strategy for designing and preparing functional NGCs for PNI treatment. Schematic illustration of the preparation process of CGA-containing GelMA microspheres (CGMs) and complex CGM/PCL nerve guide conduits (NGCs).