Enhanced sciatic nerve regeneration by relieving iron-overloading and organelle stress with the nanofibrous P(MMD-co-LA)/DFO conduits

Abstract

Wallerian degeneration after peripheral nerve injury (PNI), that is, the autonomous degeneration of distal axons, leads to an imbalance of iron homeostasis and easily induces oxidative stress caused by iron overload. Inspired by the process of nerve degeneration and regeneration, the design of a functional electrospinning scaffold with iron chelating ability exhibited the importance of reconstructing a suitable microenvironment. Here, an electrospinning scaffold based on deferoxamine and poly(3(S)-methyl-morpholine-2,5-dione-co-lactone) (PDPLA/DFO) was constructed. This work aims to explore the promotion of nerve regeneration by the physiological regulation of the scaffold. In vitro, PDPLA/DFO films mitigated the reduction of glutathione and the inactivation of Glutathione peroxidase 4 caused by iron overload. In addition, they decreased reactive oxygen species, relieve the stress of the endoplasmic reticulum and mitochondria, and reduce cell apoptosis. In vivo, PDPLA/DFO conduits constructed the anti-inflammatory microenvironment and promoted cell survival by alleviating iron overload and organelle stress. In conclusion, PDPLA/DFO guidance conduits targeted the distal iron overload and promoted nerve regeneration. It provides novel ideas for designing nerve conduits targeting the distal microenvironment.

Keywords

• Peripheral nerve regeneration
• Wallerian degeneration
• Iron overload
• Mitochondria stress
• Endoplasmic reticulum stress