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A methodology to develop a vascular geometry for in vitro cell culture using additive manufacturing
           will offer a new approach to cure SCD.  The long-   several tools or activities to exchange knowledge, such
           term  goal  of this research  is to better  understand  the   as literature reviews, informal meetings and discussions
           pathophysiology of cerebral arterial disease in SCD and   with managers, engineers, researchers, and physicians,
           possibly to discover or predict the chances of success,   punctual observations of work practices, and knowledge
           of new therapeutic  approaches. Unfortunately, animal   transfer processes . Wong  et  al. proposed to follow a
                                                                              [7]
           models do not allow the analysis of the pathophysiology   process to manage the engineering and production of
           of cerebral vasculopathy because of the huge difference   biomedical  devices.  The product development  strategy
           between animal  and human according to the vessel   includes  a product  conceptualization,  a market  survey
           geometry and the hemorheological parameters.        and the establishment of strategic alliances, the design,
             Moreover, in vitro 3D models can allow the analysis of   prototyping,  and product development,  the testing  and
           extreme conditions that can occur in pathophysiological   commissioning,  and technology protection,  through
                                                                    [8]
           conditions but are difficult to reproduce except in vitro   patents .
           conditions. A first step is to develop cell culture on a AM   Bradbury et al. provided an innovative method for rapid
           vascular geometry for in vitro studies. Actually, there are   design, manufacture, and selection of biomedical devices
           very few methodologies intended to help the designer to   such as implants or oral dosage pills using electronic data
           manufacture a vascular geometry in AM and to perform   and modeling transmissions through computer networks
                                                                                                 [9]
           in vitro cell culture on it. As the product is innovative   such as the internet, intranets or extranets .
           and highly multidisciplinary, it is mandatory to answer   A multi-dimensional  digital model may be created
           the  following research  question:  Which  methodology   based on radiological  data  and patient  information.
           should be used to develop an  AM vascular geometry   A  collaboration between clinical professionals and
           designed for cell culture in these in vitro models? This   engineers allows modification of the digital model. Once
           paper presents the design approach used to develop   the digital model is approved, it may be converted into
           this experimental product. More generally, this method   machine instructions to build the biomedical device. This
           could be applied to all human-based products designed   method  for rapid  construction of biomedical  devices
           for biological purposes using AM. Finally, a use-case is   may be applied to AM. Thus, it is necessary first of all to
           proposed to validate the method.                    analyze the medical need. Then, the knowledge between
                                                               the medical  profession and the engineers  is shared
           2. Research Objectives and Specifications           throughout the project.

           In  the  first  part  of  the  project,  the  aim  is  to  decipher   3.2. Methodologies to Design Innovative
           the biological pathways involved in the vessel damage   Products based on AM
           due to hemorheological  pathological  conditions found
           in SCD children. Previous work provided shear stress   According to Chu et al., the main role of AM technologies
           abnormalities  in  the  in  silico  study  that  should  be   is to produce “parts and devices that are geometrically
           reproduced and analyzed in a 3D model. Thanks to AM,   complex, have graded material compositions, and can
           the prototype of a vascular geometry  can be rapidly   be customized.” Besides, it is possible to build almost
           realized. Then, the effect of sheer stress in a child with   any shape with a large range of materials, which could
           SCD will be understood. The constraints established by   be difficult to produce using conventional manufacturing
                                                               methods  such as milling,  turning,  or casting. AM also
           the various stakeholders involved in this project are as   offers fabrication of parts with reduced costs and with
           follows:  The  material  must  allow to  study  in  vitro the   rapid availability .
                                                                             [10]
           interactions between the blood and the endothelium but   Bourell  et  al. advocated  to develop  new design
           also the impact of pathological speeds of the blood flow   methodologies  dedicated  to  AM: Design for  AM
           on the endothelial cells.                           (DFAM) . The most widespread definition of DFAM is
                                                                      [11]
           3. State-of-The-Art                                 a methodology which “maximize  product performance
                                                               through the synthesis of shapes, sizes, hierarchical
           3.1. Methodologies to Develop Innovative            structures, and material  compositions, subject to the
           Medical Devices                                     capabilities  of  AM technologies”  and “to  best utilize
                                                               manufacturing  process  capabilities  to  achieve  desired
           Design of innovative  complex  products  in  the  medical   performance and other life-cycle objectives” [12,13] .
           field often involves both engineers and medical experts.   Wong  and  Hernandez  presented  the  general  process
           As  innovative  medical  devices require collaboration   of AM . It is also presented by Noorani in  Figure  1.
                                                                    [14]
           between multidisciplinary teams, it is important to set up   It summarizes the stages of product development using
           a framework to transfer knowledge an efficient between   rapid  prototyping and  shows that  there  can  be several
           those two domains . Arntzen-Bechina and Leguy proposed   iterations before the final product.
                          [6]
           100                         International Journal of Bioprinting (2019)–Volume 5, Issue 2
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