Electrical stimulation with polypyrrole-coated polycaprolactone/silk fibroin scaffold promotes sacral nerve regeneration by modulating macrophage polarisation

Peripheral nerve injury poses a great threat to neurosurgery and limits the regenerative potential of sacral nerves in the neurogenic bladder. It remains unknown whether electrical stimulation can facilitate sacral nerve regeneration in addition to modulate bladder function. The objective of this study was to utilise electrical stimulation in sacra nerve crush injury with newly constructed electroconductive scaffold and explore the role of macrophages in electrical stimulation with crushed nerves. As a result, we generated a polypyrrole-coated polycaprolactone/silk fibroin scaffold through which we applied electrical stimulation. The electrical stimulation boosted nerve regeneration and polarised the macrophages towards the M2 phenotype. An in vitro test using bone marrow derived macrophages revealed that the pro-regenerative polarisation of M2 were significantly enhanced by electrical stimulation. Bioinformatics analysis showed that the expression of signal transducer and activator of transcriptions (STATs) was differentially regulated in a way that promoted M2-related genes expression. Our work indicated the feasibility of electricals stimulation used for sacral nerve regeneration and provided a firm demonstration of a pivotal role which macrophages played in electrical stimulation.