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ORIGINAL ARTICLE

           Rational Design of a Triple-Layered Coaxial Extruder

           System: in silico and in vitro Evaluations Directed

           Toward Optimizing Cell Viability


           Christian Silva *, Carlos J. Cortés-Rodriguez , Jonas Hazur , Supachai Reakasame , Aldo R. Boccaccini 2
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           1 Department  of Mechanical  Engineering  and Mechatronics,  School of Engineering,  Universidad Nacional  de Colombia,
           Bogotá 111321, Colombia
           2 Department of Materials Science and Engineering, Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen
           91058, Germany


           Abstract: Biofabrication is a rapidly evolving field whose main goal is the manufacturing of three-dimensional (3D) cell-laden
           constructs that closely mimic tissues and organs. Despite recent advances on materials and techniques directed toward the
           achievement of this goal, several aspects such as tissue vascularization and prolonged cell functionality are limiting bench-to-
           bedside translation. Extrusion-based 3D bioprinting has been devised as a promising biofabrication technology to overcome these
           limitations, due to its versatility and wide availability. Here, we report the development of a triple-layered coaxial nozzle for use in
           the biomanufacturing of vascular networks and vessels. The design of the coaxial nozzle was first optimized toward guaranteeing
           high cell viability upon extrusion. This was done with the aid of in silico evaluations and their subsequent experimental validation
           by investigating the bioprinting of an alginate-based bioink. Results confirmed that the values for pressure distribution predicted
           by in silico experiments resulted in cell viabilities above 70% and further demonstrated the effect of layer thickness and extrusion
           pressure on cell viability. Our work paves the way for the rational design of multi-layered coaxial extrusion systems to be used in
           biofabrication approaches to replicate the very complex structures found in native organs and tissues.
           Keywords: Three-dimensional bioprinting, Coaxial nozzle, Vascularized tissues, Tissue-engineered vessels, Biomaterials

           *Corresponding Author: Christian Silva, Department of Mechanical Engineering and Mechatronics, School of Engineering, Universidad
           Nacional de Colombia, Bogotá 111321, Colombia; casilvaca@unal.edu.co
           Received: May 12, 2020; Accepted: June 22, 2020; Published Online: July 24, 2020
           Citation: Silva C, Cortés-Rodriguez C, Hazur J, et al., 2020, Rational Design of a Triple-Layered Coaxial Extruder System:
           in silico and in vitro Evaluations Directed Toward Optimizing Cell Viability, Int J Bioprint, 6(4): 282. DOI: 10.18063/ijb.v6i4.282.

           1 Introduction                                      technique for achieving 3D structures of sufficient
                                                               complexity, since it can work with a broad range of
           Three-dimensional (3D) bioprinting is an additive   cell densities and printable materials [4,5] . Moreover,
           manufacturing technology that permits the           the  versatility  and  affordability  provided  by  EBB
           spatiotemporal  patterning  of hydrogels embedded
           with cells, namely bioinks, into 3D structures [1,2] .   systems have contributed to its positioning as the
           Its goal is to fabricate cell-laden constructs that   most popular biofabrication technology among
           mimic  tissues  and  organs,  where  cell  viability  is   researchers worldwide for applications that range
           preserved and overall physiological functionality   from cancer research and drug testing to tissue
                                                                         [6]
           is  replicated [1,3] .  Among  its several techniques,   engineering .
           extrusion-based  bioprinting  (EBB)  has  emerged     Replicating complex internal tissue structures
           as the most promising additive manufacturing        is, however, still  a challenge  for the available

           © 2020 Silva, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International
           License (http://creativecommons.org/licenses/by-nc/4.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the
           original work is properly cited.
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