Electrospun conductive nanofiber yarns for accelerating mesenchymal stem cells differentiation and maturation into Schwann cell-like cells under a combination of electrical stimulation and chemical induction *

Development of multifunctional tube-filling materials is required to improve the performances of the ex -isting nerve guidance conduits (NGCs) in the repair of long-gap peripheral nerve (PN) injuries. In this study, composite nanofiber yarns (NYs) based on poly(p-dioxanone) (PPDO) biopolymer and different concentrations of carbon nanotubes (CNTs) were manufactured by utilizing a modified electrospinning apparatus. We confirmed the successful incorporation of CNTs into the PPDO nanofibers of as-fabricated composite NYs. The PPDO/CNT NYs exhibited similar morphology and structure in comparison with pure PPDO NYs. However, the PPDO/CNT NYs showed obviously enhanced mechanical properties and electri-cal conductivity compared to PPDO NYs. The biological tests revealed that the addition of CNTs had no negative effects on the cell growth, and proliferation of rabbit Schwann cells (rSCs), but it better main-tained the phenotype of rSCs. We also demonstrated that the electrical stimulation (ES) significantly en-hanced the differentiation capability of human adipose-derived mesenchymal stem cells (hADMSCs) into SC-like cells (SCLCs) on the PPDO/CNT NYs. More importantly, a unique combination of ES and chemi-cal induction was found to further enhance the maturation of hADMSC-SCLCs on the PPDO/CNT NYs by notably upregulating the expression levels of SC myelination-associated gene markers and increasing the growth factor secretion. Overall, this study showed that our electrically conductive PPDO/CNT composite NYs could provide a beneficial microenvironment for various cell activities, making them an attractive candidate as NGC-infilling substrates for PN regeneration applications. Statement of significance The morphology, microstructure, and bioelectrical properties of conductive PPDO/CNT NYs have been ex-plored for guiding or controlling cell behaviors. The PPDO/CNT NYs exhibited improved mechanical prop-erties and increased electrical conductivity compared to the CNT-free PPDO NYs. They also presented an obviously enhanced biocompatibility by effectively maintaining the phenotype of rSCs. In addition, when hADMSCs were seeded and cultured on the conductive PPDO/CNT NYs, CI was demonstrated to promote the SC-related growth factor secretion of hADMSCs, and ES was demonstrated to improve the phenotypic maturation of hADMSCs into myelinating SCLCs. Moreover, the combination of CI and ES was found to fur-ther synergistically enhance the maturation of hADMSC-SCLCs. The achievement of conductive PPDO/CNT NYs shows potential for application as NGC-infilling substrates for PN regeneration. (c) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

This study developed conductive PPDO/CNT composite nanofiber yarns, demonstrating their potential for nerve regeneration applications. The PPDO/CNT NYs showed excellent mechanical properties and biocompatibility, and were able to promote cell differentiation and maturation through electrical stimulation.