Novel design and combination strategy of minocycline and OECs-loaded CeO2 nanoparticles with SF for the treatment of spinal cord injury: In vitro and in vivo evaluations

Abstract

Generally, several mechanisms influenced the secondary injury chutes following acute spinal cord injury (SCI). Though current SCI therapeutic approaches mostly target single elements in the injury chutes, they have been mostly ineffective in clinical trials. The aim of this study was to design and develop a novel cerium oxide/silk fibroin (CeO2/SF) hydrogel material loaded with minocycline (MCN) and transplantation of olfactory ensheathing cells (OEC) for SCI treatment. The prepared CeO2/SF hydrogel has an advantageous porous morphological structure and CeO2 NPs were greatly encapsulated on the surface, which was confirmed by microscopic observations. The results of in vitro analyses established favourable biocompatibility of 94.65% and 89.45%, sustained drug release rate of 89% and 58%, and significant reduction in pro-inflammatory factors for the treatments using cerium oxide loaded silk fibroin (CSF) and CeO2 NPs, respectively. Meanwhile, the administration of MCN@OEC greatly provides an efficient improvement in BBB score, decreased bladder weight, and histological improvement after SCI when compared to the control. Therefore, the combined MCN and OEC-loaded CSF hydrogel sample could be proved as a low cost, safe, and potential material for the treatment of SCI.