Nanofibrous nerve conduit-enhanced peripheral nerve regeneration Xu Jiang 1 , Ruifa Mi 2 , Ahmet Hoke 2 and Sing Yian Chew 1 * 1 Nanyang Technological University, School of Chemical & Biomedical Engineering, Singapore 637459, Singapore 2 Johns Hopkins School of Medicine, Department of Neurology, Baltimore, MD, 21205, USA Abstract Fibre structures represent a potential class of materials for the formation of synthetic nerve conduits due to their biomimicking architecture. Although the advantages of fibres in enhancing nerve regener- ation have been demonstrated, in vivo evaluation of fibre size effect on nerve regeneration remains limited. In this study, we analyzed the effects of fibre diameter of electrospun conduits on peripheral nerve regeneration across a 15-mm critical defect gap in a rat sciatic nerve injury model. By using an electrospinning technique, fibrous conduits comprised of aligned electrospun poly («-caprolactone) (PCL) microfibers (981  83 nm, Microfiber) or nanofibers (251  32 nm, Nanofiber) were obtained. At three months post implantation, axons regenerated across the defect gap in all animals that received fibrous conduits. In contrast, complete nerve regeneration was not observed in the control group that received empty, non-porous PCL film conduits (Film). Nanofiber conduits resulted in significantly higher total number of myelinated axons and thicker myelin sheaths compared to Microfiber and Film conduits. Retrograde labeling revealed a significant increase in number of regenerated dorsal root ganglion sensory neurons in the presence of Nanofiber conduits (1.93  0.71 x 10 3 vs. 0.98  0.30 x 10 3 in Microfiber, p < 0.01). In addition, the compound muscle action potential (CMAP) amplitudes were higher and distal motor latency values were lower in the Nanofiber conduit group compared to the Microfiber group. This study demonstrated the impact of fibre size on peripheral nerve regeneration. These results could provide useful insights for future nerve guide designs. Copyright © 2012 John Wiley & Sons, Ltd. Received 23 September 2011; Revised 28 February 2012; Accepted 4 April 2012 Supporting information may be found in the online version of this article. Keywords electrospinning; contact guidance; nanofibers; neural tissue engineering; sciatic nerve regeneration; critical defect gap 1. Introduction Peripheral nerve damage is a common problem associated with traumatic injuries and most patients require recon- structive surgery. However, functional recovery across large-gap lesions is often sub-optimal, particularly when empty synthetic nerve conduits are implanted. Therefore, despite the well-documented drawbacks related to autolo- gous nerve grafts (Chen et al., 2006), these implants remain the gold standard for peripheral nerve injury treatment. In an attempt to enhance the performance of synthetic conduits, pores (Vleggeert-Lankamp et al., 2007; Oh et al., 2008; Xie et al., 2008a, 2008b) and lumen fillers (Lundborg et al., 1997; Cai et al., 2005; Chew et al., 2007; Kim et al., 2008) have been introduced as potential modifications. Pores in the range of 1–20 mm can enhance nerve regenera- tion by promoting nutrient transport and blood vessel infiltration (Chang et al., 2007; Vleggeert-Lankamp et al., 2007; Wang et al., 2007a, 2007b; Oh et al., 2008; Xie et al., 2008a, 2008b) while reducing fibrous tissue invasion (Wang et al., 2009). Lumen fillers, on the other hand, provide contact guidance and enhanced surface area for cell attach- ment and growth (Chen et al., 2006; Jiang et al., 2010). In this context, fibre structures represent a potential class of materials for synthetic nerve guides due to their biomimicking architecture and have been implemented either as fillers within the lumens of nerve conduits *Correspondence to: Sing Yian Chew, Nanyang Technological University, School of Chemical & Biomedical Engineering, Singapore 637459, Singapore. E-mail: sychew@ntu.edu.sg Copyright © 2012 John Wiley & Sons, Ltd. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH ARTICLE J Tissue Eng Regen Med (2012) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/term.1531