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Electrical stimulation of neural-differentiating iPSCs on novel coaxial electroconductive nanofibers

Garrudo, F. ; Nogueira, D. E. S. ; Rodrigues, C. A. V. ; Ferreira, F. A. ; Paradiso, P. ; Colaço, R. ; Marques, A. C. ; Cabral, J. M. S. ; Morgado, J. ; Linhardt, R. J. ; Ferreira, F.C.F.

Biomaterials Science Vol. 9, Nº 15, pp. 5359 - 5382, June, 2021.

ISSN (print): 2047-4849
ISSN (online): 2047-4830

Scimago Journal Ranking: 1,24 (in 2021)

Digital Object Identifier: 10.1039/d1bm00503k

Neural tissue engineering strategies are paramount to create fully mature neurons, necessary for new
therapeutic strategies for neurological diseases or the creation of reliable in vitro models. Scaffolds can
provide physical support for these neurons and enable cues for enhancing neural cell differentiation, such
as electrical current. Coaxial electrospinning fibers, designed to fulfill neural cell needs, bring together an
electroconductive shell layer (PCL-PANI), able to mediate electrical stimulation of cells cultivated on
fibers mesh surface, and a soft core layer (PGS), used to finetune fiber diameter (951 ± 465 nm) and
mechanical properties (1.3 ± 0.2 MPa). Those dual functional coaxial fibers are electroconductive (0.063
± 0.029 S cm−1, stable over 21 days) and biodegradable (72% weigh loss in 12 hours upon human lipase
accelerated assay). For the first time, the long-term effects of electrical stimulation on induced neural
progenitor cells were studied using such fibers. The results show increase in neural maturation (upregulation
of MAP2, NEF-H and SYP), up-regulation of glutamatergic marker genes (VGLUT1 – 15-fold) and
voltage-sensitive channels (SCN1α – 12-fold, CACNA1C – 32-fold), and a down-regulation of GABAergic
marker (GAD67 – 0.09-fold), as detected by qRT-PCR. Therefore, this study suggest a shift from an inhibitory
to an excitatory neural cell profile. This work shows that the PGS/PCL-PANI coaxial fibers here developed
have potential applications in neural tissue engineering.