Please cite this article in press as: D.O.C.Wu, D.O.C. Biomimetic nanoﬁbrous scaffolds for neural tissue engineering and drug development, Drug Discov Today (2017), http://dx.doi.org/ 10.1016/j.drudis.2017.03.007 Drug Discovery Today  Volume 00, Number 00  April 2017 REVIEWS Biomimetic nanofibrous scaffolds for neural tissue engineering and drug development Jing Wu Q1 1,3 , Lili Xie 2 , William Zhi Yuan Lin 4 and Qiushui Chen 3 1 School of Science, China University of Geosciences (Beijing), Beijing, China 2 College of Chemistry, Fuzhou University, Fuzhou, China 3 Department of Chemistry, National University of Singapore, Singapore 4 Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, Canada Neural tissue engineering aims to develop functional substitutes for damaged tissues, creating many promising opportunities in regeneration medicine and drug discovery. Biomaterial scaffolds routinely provide nerve cells with a physical support for cell growth and regeneration, yielding 3D extracellular matrix to mimic the in vivo cellular microenvironment. Among the various types of cellular scaffolds for reconstruction, biomimetic nanoﬁbrous scaffolds are recognized as appropriate candidates by precisely controlling morphology and shape. Here, we review the current techniques in fabricating biomimetic nanoﬁbrous scaffolds for neural tissue engineering, and describe the impact of nanoﬁber components on the properties of scaffolds and their uses in therapeutic models and drug development. We also discuss the current challenges and future directions of applying 3D printing and microﬂuidic technologies in neural Q2 tissue engineering. Introduction The ability to reconstruct artiﬁcially Q3 functional 3D tissues or organs has been recognized as an important technology for ani- mal-alternative drug screening and regenerative medicine [1–3]. Neural tissue engineering offers new therapeutic opportunities for regenerating the damaged nervous tissues in transplantation, and also creates in vitro 3D neural models for drug screening [4–6]. In these studies, biomaterial scaffolds are generally required to provide an artiﬁcial extracellular matrix (ECM) for the seeding and growth of nerve cells. Rather than simply mixing cells with biomaterials, an effective technique for neural tissue engineering often combines nano- and micro-technological strategies for designing and engineering complex tissues, and tailoring the properties of 3D biological scaffolds; this is crucial for a successful reconstruction to mimic the real cellular microenvironment and reproduce effective tissue functions [7,8]. Therefore, signiﬁcant efforts have been devoted to promote effective organization and functional integration of the cells into biological scaffolds with closely resembled morphological and physiological features in vivo [9–11]. Q4 In recent years, many advanced strategies for neural tissue engineering have been developed, especially in fabricating bio- mimetic nanoﬁbrous scaffolds used to mimic the ECM [12,13]. The current technologies have enabled precise control of the nanoscale morphologies and tune the biochemical properties of nanoﬁber biomaterials for tissue engineering [14]. In particular, among the materials used for neural tissue engineering, nanoﬁ- brous scaffolds have been widely used because of their high surface-area:volume ratio and close imitation of the natural ECMs [15–17]. At the same time, the development of nanoﬁbers greatly extends the scope of fabricating biological scaffolds, and solves the problem of cell loss or neuropathy caused by nonphysiological local stress [13,18]. It is believed that these artiﬁcial biomaterials can serve as necessary tissue scaffolds for engineering functional neural tissues [19]. Nowadays, current technological development in biomimetic nanoﬁbrous scaffolds has promoted many biomedical applications of neural tissue Reviews  POST SCREEN Corresponding authors: Wu, J. (wujing@cugb.edu.cn), Xie, L. (yubingdian@163.com), Chen, Q. (chmcq@nus.edu.sg), (cqs09@mails.tsinghua.edu.cn) 1359-6446/ã 2017 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.drudis.2017.03.007 www.drugdiscoverytoday.com 1