Biofabrication for neural tissue engineering applications L. Papadimitriou a, c , P. Manganas a, c , A. Ranella a, ** , E. Stratakis a, b, * a Institute of Electronic Structure and Laser (IESL), Foundation for Research and Technology-Hellas (FORTH), Heraklion, 71003, Greece b Physics Department, University of Crete, Heraklion, 71003, Crete, Greece ARTICLE INFO Keywords: Amniotic membrane Biofabrication Neural tissue engineering Lab-on-a-chip Central nervous system Peripheral nervous system Neural regeneration Scaffolds ABSTRACT Unlike other tissue types, the nervous tissue extends to a wide and complex environment that provides a plurality of different biochemical and topological stimuli, which in turn defines the advanced functions of that tissue. As a consequence of such complexity, the traditional transplantation therapeutic methods are quite ineffective; therefore, the restoration of peripheral and central nervous system injuries has been a continuous scientific challenge. Tissue engineering and regenerative medicine in the nervous system have provided new alternative medical approaches. These methods use external biomaterial supports, known as scaffolds, to create platforms for the cells to migrate to the injury site and repair the tissue. The challenge in neural tissue engineering (NTE) remains the fabrication of scaffolds with precisely controlled, tunable topography, biochemical cues, and surface energy, capable of directing and controlling the function of neuronal cells toward the recovery from neurological disorders and injuries. At the same time, it has been shown that NTE provides the potential to model neurological diseases in vitro, mainly via lab-on-a-chip systems, especially in cases for which it is difficult to obtain suitable animal models. As a consequence of the intense research activity in the field, a variety of synthetic approaches and 3D fabrication methods have been developed for the fabrication of NTE scaffolds, including soft lithography and self-assembly, as well as subtractive (top-down) and additive (bottom-up) manufacturing. This article aims at reviewing the existing research effort in the rapidly growing field related to the development of biomaterial scaffolds and lab-on-a-chip systems for NTE applications. Besides presenting recent advances achieved by NTE strategies, this work also delineates existing limitations and highlights emerging possibilities and future prospects in this field. 1. Introduction The nervous tissue consists of the central nervous system (CNS) and the peripheral nervous system (PNS) and is the most complex system in the body. Injuries to the human nervous system affect more than 1 billion people around the world, with 6.8 million dying as a result of them each year [1], and have been associated with a wide variety of disorders including neurodegenerative diseases, as well as brain and spinal cord (SC) traumatic injuries and stroke [2]. The central nervous tissue does not regenerate under normal conditions, and to date, there is no treat- ment modality with clinically documented efficacy to actively improve CNS repair. Current medical approaches focus primarily on stabilization and prevention, e.g., orthopedic fixation of an unstable spine, and consequently on rehabilitation and the preparation of prosthetics. On the contrary, the management of a PNS injury is much simpler. The currently applied treatments involve nerve autografts and allografts; however, there are many difficulties, including shortage of donor nerves, donor-- site morbidity, aberrant regeneration, infectious diseases, and immuno- logical issues [3]. It is therefore understood that there is a vital need for engineered alternatives to autograft application [4]. In view of the ineffectiveness of current therapeutic methods, the restoration of the damaged PNS and CNS has been a continuous challenge for neurologists and neurobiologists. As a result, novel treatment stra- tegies for the injured nervous system have been pursued. Tissue engi- neering and regenerative medicine in the nervous system have provided new medical approaches as alternatives to traditional transplantation methods. These methods use external biomaterial supports, known as scaffolds, to create a platform for the cells to migrate to the injury site and repair the tissue. Three-dimensional (3D) scaffold models have been found to be critical for mimicking the exact microcellular environment * Corresponding author. ** Corresponding author. E-mail addresses: ranthi@iesl.forth.gr (A. Ranella), stratak@iesl.forth.gr (E. Stratakis). c These authors contributed equally to this work. Contents lists available at ScienceDirect Materials Today Bio journal homepage: www.journals.elsevier.com/materials-today-bio https://doi.org/10.1016/j.mtbio.2020.100043 Received 2 December 2019; Received in revised form 22 January 2020; Accepted 23 January 2020 Available online 30 January 2020 2590-0064/© 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Materials Today Bio 6 (2020) 100043