Schwann cell response on polypyrrole substrates upon electrical stimulation Leandro Forciniti b , Jose Ybarra III a , Muhammad H. Zaman c , Christine E. Schmidt d,⇑ a Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, MC C0800, Austin, TX 78712, USA b Department of Chemical Engineering, The University of Texas at Austin, 1 University Station, MC C0400, Austin, TX 78712, USA c Department of Biomedical Engineering, Boston University, 38 Cummington Street, Boston, MA 02215, USA d J. Crayton Pruitt Family Department of Biomedical Engineering, The University of Florida, 1275 Center Drive, Gainesville, FL 32611, USA article info Article history: Received 29 October 2013 Received in revised form 21 December 2013 Accepted 28 January 2014 Available online xxxx Keywords: Schwann cell migration Polypyrrole Protein adsorption Electrically mediated cell migration abstract Current injury models suggest that Schwann cell (SC) migration and guidance are necessary for successful regeneration and synaptic reconnection after peripheral nerve injury. The ability of conducting polymers such as polypyrrole (PPy) to exhibit chemical, contact and electrical stimuli for cells has led to much interest in their use for neural conduits. Despite this interest, there has been very little research on the effect that electrical stimulation (ES) using PPy has on SC behavior. Here we investigate the mechanism by which SCs interact with PPy in the presence of an electric field. Additionally, we explored the effect that the adsorption of different serum proteins on PPy upon the application of an electric field has on SC migration. The results indicate an increase in average displacement of the SC with ES, resulting in a net anodic migration. Moreover, indirect effects of protein adsorption due to the oxidation of the film upon the application of ES were shown to have a larger effect on migration speed than on migration directionality. These results suggest that SC migration speed is governed by an integrin- or receptor-med- iated mechanism, whereas SC migration directionality is governed by electrically mediated phenomena. These data will prove invaluable in optimizing conducting polymers for their different biomedical appli- cations such as nerve repair. Ó 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Currently it is believed that Schwann cell (SC) migration pre- cedes and enhances axonal repair in the peripheral nervous system [1,2]. Migration from both the distal and proximal ends of injury sites have been observed in vivo [2]. Furthermore these migratory cells have been shown to guide axon reinnervation [2], control syn- aptic formation [3] and induce faster axon regeneration [1]. This has led to interest in understanding how different external cues presented by biomaterials impact SC migration. Soluble chemical factors affect SC migration at several different levels. Numerous growth factors are known to mitigate SC migra- tion. These include growth factors that promote migration such as nerve growth factor (NGF) [4], glial growth factor II [3,5], insulin- like growth factor 1 [6], and b neuregulin as well as growth factors that inhibit migration such as brain-derived neurotrophic factor (BDNF) [7]. In addition to growth factors, complex sugars and pro- teoglycans have been shown to promote SC migration [8]. Contact guidance and force mitigated mechano-transduction also have an important role in SC migration and maturation. Lam- inin 1, laminin 2 (merosin) and fibronectin (FN) all interact with integrins to promote migration. Specifically, Milner et al. showed that laminin 1 and 2 promote SC migration through b1 integrins, whereas FN promotes migration through a5 integrins [9]. Further- more, aligned collagen gels [10] and collagen:poly((epsilon)-capro- lactone) gels [11] have been shown to promote and orient migration. Mechanistically, this contact guidance is thought to oc- cur through mechano-transduction. Specifically, Chew et al. [11] used microarray analysis to demonstrate that aligned SCs cultured on patterned substrates down-regulate the expression of neurotro- phins and neurotrophic receptors while up-regulating the expres- sion of myelin specific gene (P0). Furthermore, Rosner et al. [10] showed that by introducing transforming growth factor b1 into cell culture medium, SCs could more accurately detect the aligned col- lagen fibrils through the up-regulation of b1 integrins. SCs have multiple means by which they interact with electrical cues. Of these the most basic is their interaction with electrical cues through voltage-activated ion channels. SCs contain several types of voltage-activated ion channels, including sodium chan- nels, two types of calcium channels (HVA Ca 2+ ; LVA Ca 2+ ), four http://dx.doi.org/10.1016/j.actbio.2014.01.030 1742-7061/Ó 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Tel.: +1 352 273 9222. E-mail address: schmidt@bme.ufl.edu (C.E. Schmidt). Acta Biomaterialia xxx (2014) xxx–xxx Contents lists available at ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat Please cite this article in press as: Forciniti L et al. Schwann cell response on polypyrrole substrates upon electrical stimulation. Acta Biomater (2014), http://dx.doi.org/10.1016/j.actbio.2014.01.030