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A methodology to develop a vascular geometry for in vitro cell culture using additive manufacturing
           prevent it from being marketable on a large scale. However,   •   Optimization of the product with iterations
           the disadvantages of PDMS are the absorption of small   •   Final validation
           molecules, the manufacturing method incompatible with   •   Make sure the product is correctly used
           mass production and also its reversible hydrophilicity.  •   Tests  prototype  and  medical  return  to  improve  the
             Lachaux et al. found a new polymer (Flexdym) offering   model.
           flexibility and translucent comparable to PDMS. Flexdym   Thus,  in  this  article,  an  innovative  methodology
           is a copolymer block solution, composed of Di or Triblock   to achieve a complex  vascular geometry  using  AM
           according to the different grade. It is similarities with the   is proposed.  As mentioned  before,  there  are  few
           PDMS but without the drawbacks. Easy and inexpensive   methodologies  that  combine  the realization  of medical
           microstructuration  method,  microfluidic  devices  are   devices  and AM processes. Existing  methodologies  do
           fabricated in less than a minute .                  not propose to simplify the complex geometry to allow
                                     [21]
             Furthermore,  microfabrication  can be performed   faster validation of all subsequent steps such as the choice
           using a hot-embossing machine or a very simple press   of material or the cellular study. Here, we can proceed
           equipment; downstream Flexdym is amenable for rapid   with iteration  loops and improve our design each  time
           manufacturing  technology such as injection  molding.   to  finally  fulfill  the  complex  form. Thus,  the  proposed
           Flexdym can be bonded easily without surface treatments   method can be adapted to any case study.
           and pressure loads, thanks to is mechanical properties.
             Sealing can be achieved either on a simple hot plate or   4. A Methodology to Develop Vascular
           even at room temperature. It is flexible and thus allows   Geometry for In Vitro Cell Culture using
           cutting into small pieces. It is translucent and biocompatible   AM: AM-Biopart
           which will allow the study of cell culture. Due to its
           bonding qualities, two-part molding is envisaged.   The proposed method (Figure 5) is based on important
             Recently, cell  culture  studies have  been  released  on   points told in the synthesis that chosen from the existing
           VeroClear, AM material. Lu et al. used Veroclear because   methods seen previously.
           of its good formation  properties and high precision.   The  method  proposed  by  Lenoir  et  al.  (2019)  is
           However, the interactions  between cells and materials   divided into four steps. The first “Initialization” consists
           are affected by topography and surface chemistry of the   of understanding and summarizing the objectives, needs,
           implant materials,  such as roughness  and hydrophilic   and  constraints  desired  by  the  medical  profession.
           properties .                                        Knowledge is capitalized and well transferred between
                   [22]
             In this study, authors have developed  a method   engineers and health professionals.
           of coating waterborne polyurethane  (WPU) onto the    Then, Step II, “concept and feasibility” allow to search
           Veroclear resin to improve the biocompatibility.  WPU   and define the different manufacturing methods and then
           (Safe polymeric  material)  is a coating  material  for   to know their costs.
           creating  barriers between corrosive environments and   For Step III, “design and development”  is more
           material surfaces. WPU has been used in medical implants   complex.  Geometry  simplification  strategy  is  included
           because of its low toxicity, good biocompatibility, and   (Step  III,  1)  to  allow  engineers  to  focus  first  on  the
           coating characteristics.                            material to be used that meets the different constraints.
                                                                 Once these parameters have been approved (Step III, 8),
           3.4. Synthesis                                      the geometry can be made more complex (Step III, 9).
           Only a few papers rely  on AM to produce  biomedical   Then, the whole process can start again (Steps III, 2) to
           parts. This paper highlights existing methodologies  for   (Steps III, 7), through an improvement of the design, until
           designing innovative products based on AM, others that   the final validation of the realistic 3D model.
           can help develop innovative medical devices. However, it   Finally, during the last step, the design is optimized
           is difficult to find a methodology that combines these two   by performing user tests. At the end, once everything is
           aspects; there are only a few at the intersection of these   validated  and optimized,  only training for clinical  use
           two technologies.                                   remains.
             The interesting points of these different methodologies   5. Use Case AM-Biopart Adapted to the
           are:                                                Manufacturing of a Carotid
           •   Well understand the goals and needs of the user
           •   Engineers  and  health  professionals  pool  their   In this section, the method is tested on the manufacturing
              knowledge throughout the project                 of a carotid  (Figure  6)  in  vitro to  understand  the
           •   Strategic  choice  and  plan  of  manufacturing  before   physiopathology.
              prototyping                                        This carotid  was modeled  by  ARM (Figure  7), on
           •   Design by performing user tests                 a  sickle  cell  child.  ARM  is  an  exam  that  specifically

           104                         International Journal of Bioprinting (2019)–Volume 5, Issue 2
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