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RESEARCH ARTICLE

           Bioprinting of Human Neural Tissues Using a

           Sustainable Marine Tunicate-Derived Bioink for

           Translational Medicine Applications


           Soja Saghar Soman , Mano Govindraj , Noura Al Hashimi , Jiarui Zhou , Sanjairaj
                                                                      1
                               1
                                                 1
                                                                                   1,2
           Vijayavenkataraman *
                                1,2
           1 The Vijay Lab, Division of Engineering, New York University Abu Dhabi, Abu Dhabi, UAE
           2 Department of Mechanical and Aerospace Engineering, Tandon School of Engineering, New York University, Brooklyn, USA
           Abstract: Bioprinting of nervous tissue is a major challenge in the bioprinting field due to its soft consistency and complex
           architecture. The first step in efficient neural bioprinting is the design and optimization of printable bioinks which favor
           the  growth  and  differentiation  of  neural  tissues  by  providing  the  mechanophysiological  properties  of  the  native  tissue
           microenvironment. However, till date, limited studies have been conducted to make tissue specific bioinks. Here, we report
           a novel bioink formulation specifically designed for bioprinting and differentiation of neural stem cells (NSCs) to peripheral
           neurons, using a marine tunicate-derived hydrogel and Matrigel. The formulation resulted in seamless bioprinting of NSCs
           with minimal processing time from bioink preparation to in vitro culture. The tissues exhibited excellent post-printing viability
           and cell proliferation along with a precise peripheral nerve morphology on in vitro differentiation. The cultured tissues showed
           significant cell recovery after subjecting to a freeze-thaw cycle of −80 to 37°C, indicating the suitability of the method for
           developing tissues compatible for long-term storage and transportation for clinical use. The study provides a robust method to
           use a sustainable bioink for three-dimensional bioprinting of neural tissues for translational medicine applications.

           Keywords: 3D bioprinting; Neural stem cells; Peripheral neurons; Sustainable bioink; Extrusion bioprinting

           Correspondence to: Sanjairaj Vijayavenkataraman, The Vijay Lab, Division of Engineering, New York University Abu Dhabi, Abu Dhabi, P.O.
           Box 129188, UAE; vs89@nyu.edu

           Received: April 26, 2022; Accepted: June 16, 2022; Published Online: August 23, 2022
           Citation: Soman SS, Govindraj M, Al Hashimi N, et al., 2022. Bioprinting of Human Neural Tissues Using a Sustainable Marine Tunicate-
           Derived Bioink for Translational Medicine Applications, 8(4):604. http://doi.org/10.18063/ijb.v8i4.604

           1. Introduction                                     the body. Injury to peripheral nerves is a very common
                                                               neurological  disease  that  is generally  caused  by direct
           Our understanding of the nervous system disorders and   mechanical  trauma or degeneration.  The self-repairing
           its therapeutic  developments  majorly  depends on the   ability of peripheral nerves is limited and nerve injury can
           animal models and two-dimensional cell culture systems.   lead to life-long disability. 3D bioprinting of peripheral
           Most of these traditional  models cannot address the   nerves is a promising technology to engineer peripheral
           questions that pertain  to species variations,  sensitivity,   nerve tissues for treatment as well as disease modeling.
           and  complexity  of  the  human  nervous  system.  These   Stem  cell  technology  combined  with  bioprinting  offer
           limitations demand a more realistic in vitro human model   important tools to make viable peripheral nerve conduits
           to study the nervous system. Biomaterials engineering,   and nerve tissues [1-3] .
           three-dimensional  (3D)  biofabrication,  and  stem  cell   3D  bioprinting  requires  the  use  of  biocompatible
           technology can help design innovative tissue systems that   bioinks,  which  must  be  optimized  to  favor  the
           can be used to model the physiology and pathobiology of   differentiation and growth of specific cell types for the
           human nervous system. Peripheral nervous system is a   formation of target tissues. The viscoelastic properties of
           complex network of elongated nerves running throughout   the bioink can be tuned for printing specific tissue types

           © 2022 Author(s). This is an Open-Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
           reproduction in any medium, provided the original work is properly cited.
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