Nerve tissue regeneration based on magnetic and conductive bifunctional hydrogel scaffold

Abstract

The growth of neurons is often influenced by magnetic and electrical physical factors, and there is more and more research focused on designing a magnetic and conductive engineering scaffolds for nerve injury repair. In this study, electrospun poly lactic-co-glycolic acid (PLGA) fibers containing Fe3O4 magnetic nanoparticles were cryo-cut into magnetic short fibers (MSFs) and subsequently incorporated into sodium alginate (SA)/carboxymethyl chitosan (CMCS) hydrogel along with the addition of multi-wall carbon nanotubes (MWCNTs). MSFs can also achieve alignment by external magnetic fields within the hydrogel to construct magnetic and conductive bifunctional MSF/MWCNT/SA/CMCS hydrogel with anisotropic structure. The magnetic-conductive bifunctional hydrogel exhibited good magnetic responsiveness, electrically active and mechanical property, in which both conductivity and mechanical property increased with the enhancement of MWCNTs contents. Notably, appearing of aligned structure significantly promoted the mechanical property of MSF/SA/CMCS hydrogel. The MSF/SA/CMCS hydrogel with aligned structure also facilitated greater primary neuron cells proliferation than random ones. Compared with individual magnetic or conductive hydrogel, there was significant increase of cell viability in the primary cultured cortical neurons on MSF/MWCNT/SA/CMCS hydrogel with aligned structure. Simultaneously, electrical stimulation (ES) combined with magnetic stimulation (MS) delivered via magnetic and conductive bifunctional MSF/MWCNT/SA/CMCS hydrogel with aligned structure produced a better effect on promoting neuronal growth compared with individual ES or MS. Besides, hot plate measurement indicated that MSF/MWCNT/SA/CMCS hydrogel with aligned structure and MS significantly decreased the mice licking latency after sciatic nerve injury. Animal behavior studies confirmed the protective role of synergistic MS with magnetic hydrogel. Such hydrogel scaffolds have long term potential for nerve tissue regeneration.