Shell-core-structured electrospinning film with sequential anti-inflammatory and pro-neurogenic effects for peripheral nerve repairment

Abstract

Inducing an anti-inflammatory response before neurogenesis is crucial in effectively addressing peripheral nerve damage. Herein, we developed shell-core-structured nanofilms (Cur/PLCL@BDNF/CNT) using poly-(l-Lactide)-Caprolactone (PLCL) and curcumin (Cur, an anti-inflammatory agent) as the shell layer, and carbon nanotubes (CNT) and brain-derived neurotrophic factor (BDNF, a neurogenic factor) as the core via coaxial electrospinning technology. The resulting Cur/PLCL@BDNF/CNT film exhibited a characteristic fibrous structure with remarkable shell-core architecture, demonstrating unweakened mechanical properties. Notably, it displayed sustained release kinetics with distinct stages: prioritized Cur release within the initial 12 days and delayed BDNF release between 10 to 30 days. Additionally, the Cur/PLCL@BDNF/CNT film demonstrated high biocompatibility with Schwann cells. Subsequent in vitro analysis revealed the potent anti-inflammatory capabilities of the released Cur from the shell layer, while the BDNF released from the core layer effectively induced neurogenic differentiation of Schwann cells. The Cur/PLCL@BDNF/CNT film was rolled into a nerve conduit and then utilized for nerve regeneration in a 10 mm rat sciatic nerve defect model. The staged release of Cur and BDNF facilitated by the Cur/PLCL@BDNF/CNT film established an anti-inflammatory microenvironment before initiating nerve regeneration, resulting in better nerve restoration. This study emphasizes the significance of shell-core-structured nanofilms in temporally regulating anti-inflammation and neurogenesis.

Keywords

• shell-core structure
• sequential control
• neurogenesis