3D-Printed PCL/PPy Conductive Scaffolds as Three-Dimensional Porous Nerve Guide Conduits (NGCs) for Peripheral Nerve Injury Repair.

Sanjairaj Vijayavenkataraman,Tong Cao,Wen Feng Lu,Jerry Y H Fuh,Sathya Kannan,Gopu Sriram

doi:10.3389/fbioe.2019.00266

Abstract

Conductivity is a desirable property of an ideal nerve guide conduit (NGC) that is being considered for peripheral nerve regeneration. Most of the conductive polymers reported in use for fabrication of tissue engineering scaffolds such as polypyrrole (PPy), polyaniline, polythiophene, and poly(3,4-ethylenedioxythiophene) are non-biodegradable and possess weak mechanical properties to be fabricated into 3D structures. In this study, a biodegradable and conductive block copolymer of PPy and Polycaprolactone (PPy-b-PCL) was used to fabricate 3D porous NGCs using a novel electrohydrodynamic jet 3D printing process which offers superior control over fiber diameter, pore size, porosity, and fiber alignment. PCL/PPy scaffolds with three different concentrations of PPy-b-PCL (0.5, 1, and 2% v/v) were fabricated as a mesh (pore size 125 ± 15 μm) and the effect of incorporation of PPy-b-PCL on mechanical properties, biodegradability, and conductivity of the NGCs were studied. The mechanical properties of the scaffolds decreased with the addition of PPy-b-PCL which aided the ability to fabricate softer scaffolds that are closer to the properties of the native human peripheral nerve. With increasing concentrations of PPy-b-PCL, the scaffolds displayed a marked increase in conductivity (ranging from 0.28 to 1.15 mS/cm depending on concentration of PPy). Human embryonic stem cell-derived neural crest stem cells (hESC-NCSCs) were used to investigate the impact of PPy-b-PCL based conductive scaffolds on the growth and differentiation to peripheral neuronal cells. The hESC-NCSCs were able to attach and differentiate to peripheral neurons on PCL and PCL/PPy scaffolds, in particular the PCL/PPy (1% v/v) scaffolds supported higher growth of neural cells and a stronger maturation of hESC-NCSCs to peripheral neuronal cells. Overall, these results suggest that PPy-based conductive scaffolds have potential clinical value as cell-free or cell-laden NGCs for peripheral neuronal regeneration.

Highlights

Scaffolds play an integral role in tissue engineering and regeneration by providing the structural support and mechanical cues for the adhesion, growth, proliferation, and differentiation of cells (O’brien, 2011; Vijayavenkataraman et al, 2017)
There are previous works reported on conductive electrospun scaffolds for tissue engineering of neural, cardiac, and skeletal muscles, where a conducting polymer is mixed with other electrospinnable polymers are fabricated into nanofibrous scaffolds
Better mechanical properties were observed with the rolled nerve guide conduit (NGC) structure shown in Figure 6 than that of the as-printed scaffolds in the degradation study (Table 2), the aim of which was to assess the influence of PPy-b-PCL addition on degradation more accurately

Summary

INTRODUCTION

Scaffolds play an integral role in tissue engineering and regeneration by providing the structural support and mechanical cues for the adhesion, growth, proliferation, and differentiation of cells (O’brien, 2011; Vijayavenkataraman et al, 2017). There are previous works reported on conductive electrospun scaffolds for tissue engineering of neural, cardiac, and skeletal muscles, where a conducting polymer is mixed with other electrospinnable polymers are fabricated into nanofibrous scaffolds Some of these works include electrospinning of PPyPolyethylene Oxide (PEO) (Chronakis et al, 2006), PANI-gelatin (Li et al, 2006), PANI-Polycaprolactone (PCL) (Chen et al, 2013), PANI-PCL-gelatin (Ghasemi-Mobarakeh et al, 2009), and PPy-Poly(lactic acid) (PLA) (Zong et al, 2005). In these studies, the conductive scaffolds were found beneficial to the neural cell proliferation, growth, and differentiation, there are a few limitations. One-way ANOVA test and Independent 2-sample t-test were used to determine the differences between the mean values of the experimental groups Differences (statistically significant at p < 0.05)

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT