Conductive conduit based on electrospun poly (l-lactide-co-D, l-lactide) nanofibers containing 4-aminopyridine-loaded molecularly imprinted poly (methacrylic acid) nanoparticles used for peripheral nerve regeneration

Abstract

Using biocompatible polymer nanofibrous conduits with a controlled drug delivery have attracted much attention for peripheral nerve regeneration. This work was aimed at preparing electrospun poly (l-lactide-co-D, l-lactide) (PLDLLA) containing multi-walled carbon nanotubes (MWCNTs) and 4-aminopyridine (4-AP)-loaded molecularly imprinted nanoparticles (MIP4-AP) as well as evaluating their performance in in vitro and in vivo assessments. After synthesis of MIP4-AP based on poly (methacrylic acid) with imprinting factor of 1.78, it was incorporated into the PLDLLA/MWCNTs nanofibers to optimize. By adjusting the process variables, the average diameter and electrical conductivity of the nanofibrous sample were 92 nm and 2870 × 10−7 S cm−1, respectively. Afterward, 4-AP release of the optimum sample showed the presence of MIP4-AP leading to initial burst release decrease and plateau level postpone up to 96 h. Moreover, the culture results of PC12 as neuroblastoma cell line on optimal PLDLLA/MWCNTs/MIP4-AP nanofibrous sample revealed the highest cell proliferation without cytotoxicity compared to neat nanofibers. Eventually, the animal model experiment exhibited that the conductive conduit based on the optimum sample was able to repair the rat's sciatic nerve after four weeks in accordance with sciatic function index and histological studies.