Abstract

Poly (L-lactic acid) (PLLA) is a biodegradable and biocompatible polymer that has been put forward as a promising material for therapeutic approaches aiming to restore neuronal function. The topographic cues present in PLLA-based scaffolds, defined by the technique used in their preparation, have been shown to play a role on the cellular behavior of adherent cells. Even though this interaction has been shown to influence the regenerative output of the scaffold, there is a lack of studies addressing this response at the proteomic level. Hence, this work focuses on the effect of electrospun PLLA-based nanofibers on the proteome, cellular processes and signaling pathways of SH-SY5Y neuroblastoma cells. It also further explores how these molecular mediators might influence cell proliferation and differentiation upon in vitro culture. For that, mass spectrometry followed by bioinformatics analysis was firstly performed and further complemented with Western blot, cell viability and imaging assays. Results show that PLLA nanofibers differentially activate and inhibit specific cellular functions and signaling pathways related to cell division, apoptosis, actin remodeling, among others. These ultimately block cellular proliferation and induce morphological rearrangements through cytoskeleton remodeling, adaptations that turn cells more prone to differentiate. In synthesis, PLLA nanofibers shift the SH-SY5Y cells proteome towards a state more responsive to differentiation-inductive cues such as the retinoic acid. Unveiling cells responses to nanomaterials is an important step to increase the tools available for their manipulation and potentiate their use in neural tissue engineering. Further studies should be performed to compare the effects of other topographic cues on cellular behavior.

Highlights

  • The development of scaffolds that provide cues to induce faster tissue regeneration is a major field of tissue engineering

  • Poly (L-lactic) acid (PLLA) scaffolds are piezoelectric biodegradable materials that when electrospun as nanofibers can provide topographic cues known to promote differentiation [2,3]

  • In this work we explored the cellular responses elicited by PLLA-based nanofibers (“NanoF”) that might underlie their ability to promote neuronal differentiation

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Summary

Introduction

The development of scaffolds that provide cues to induce faster tissue regeneration is a major field of tissue engineering. Biodegradable scaffolds based on materials such as polyglycolic acid, type-I collagen, and poly(85:15/L:D) lactide-ɛ-caprolactone have been used for nerve regeneration purposes [1,2,3] These platforms aim to improve adhesion, proliferation and differentiation of neuronal precursor cells and neurons, and may include chemical and physical cues that optimize those processes. Examples of nanofibrous piezoelectric scaffolds used to enhance cellular neuritogenesis include scaffolds based on annealed polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE). These can enhance neuritic extension in dorsal root ganglion [13] and promote differentiation of human neural progenitor cells [14].

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