Material properties and electrical stimulation regimens of polycaprolactone fumarate–polypyrrole scaffolds as potential conductive nerve conduits

Abstract

Mechanical and electrical properties of polycaprolactone fumarate-polypyrrole (PCLF-PPy) scaffolds were studied under physiological conditions to evaluate their ability to maintain material properties necessary for application as conductive nerve conduits. PC12 cells cultured on PCLFPPy scaffolds were stimulated with regimens of 10 μA of constant or 20 Hz frequency current passed through the scaffolds for 1 h/day. PC12 cellular morphologies were analyzed by fluorescence microscopy after 48 h. PCLF-PPy scaffolds exhibited excellent mechanical properties at 37°C which would allow suturing and flexibility. The surface resistivity of the scaffolds was 2kΩ and the scaffolds were electrically stable during application of electrical stimulation (ES). In vitro studies showed significant increases in percentage of neurite bearing cells, number of neurites per cell and neurite length in the presence of ES compared to no ES. Additionally, extending neurites were observed to align in the direction of the applied current. This study shows that electrically conductive PCLF-PPy scaffolds possess material properties necessary for application as nerve conduits. Additionally, the capability to significantly enhance and direct neurite extension by passing electrical current through PCLF-PPy scaffolds renders them even more promising as future therapeutic treatments for severe nerve injuries.

Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer

“…4e). This stimulation time was significantly longer than those reported from most previously conducted cell-based electrical stimulation experiments 20,24,[27][28][29][30] . In contrast, greater than 40% of the cells detached from unfunctionalized PEDOTs after only 1 day of electrical stimulation at an even lower voltage (20 mV).…”

“…7) also revealed similar conclusion because greater number of long neurites were presented. This increase is significantly greater than not only the values (20-60%) typically reported on hybrid and functionalized conducting organic materials 20,[27][28][29][30] but also the largest increase (90%) previously reported on polypyrrole 24 . We attribute this behaviour to the integrated stimulation of surface biochemical ligands and applied electrical pulses.…”

“…3b). PC12 cells are commonly employed as a model system for studies of neuronal development and function; they are also a robust model cell line for evaluating the performance of various platforms for electrically stimulated neurite outgrowth 24,[27][28][29][30] . To compare the performance of our materials with that of other reported platforms, we also adopted PC12 cells in this study to investigate neuron adhesion and differentiation.…”

“…Subsequently, various means of integrating ECPs and biofunctional groups, through physical mixing or chemical immobilization, have been tested [27][28][29][30] . For example, Schmidt and coworkers 27 coated electrospun poly(lactic-co-glycolic acid) nanofibres with polypyrrole and applied this material for neural engineering.…”

Sciatic nerve repair using poly(ε‐caprolactone) tubular prosthesis associated with nanoparticles of carbon and graphene

“…When there are significant gaps created by retraction or by extensive nerve damage resulting in loss of a nerve segment, grafts are required (Moroder et al, 2011). However, nerve autografts have some disadvantages, such as availability of donor tissue, the formation of painful neuromas in the donor area, and loss of donor nerve function (Bockelmann et al, 2011;Evans, 2000;Moroder et al, 2011;Nakamura et al, 2004;Pierucci, de Duek, & de Oliveira, 2008).…”