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Optimized vascular network by stereolithography for tissue engineered skin




















                                                      (A)                                                             (B)                                                              (C)

           Figure 2. Distributed configuration of the vascular network with different branching levels: A) 2 levels, B) 3 levels and C) 4 levels.

                                                 th
           The position of a point    belonging to the   branching
           level and being the   th  on it are given by the equation
           below:                                                                                                        (6)

                                                                                                (2)  where D is the nutrient diffusion coefficient rate which
                                                               is selected as             , C is the concentration
                                                               of the nutrient,   is a characteristic metabolic time which
                                                                                                   [39]
           where,  A is the width of the skin patch, B is the length   is depend on cells. Experimental studies   show that
           of the skin patch. This configuration is selected because   the metabolic rate of glucose in adipose tissue is around
           it shows less sharp turns than Kamiya’s configuration ,   500 s and in skeletal muscle is approximately 545 s.
                                                        [38]
           which minimised the volume of the vascular system. It   The metabolic time and the diffusion coefficient can be
           also shows less agglomeration close to the branching   combined in a characteristic length called “penetration
           points. The pressure drop at each branching point in the   depth”    defined as:
           same level is set to be identical:                                                                                        (7)
                                                                                   (3)  We define a parameter P to measure the performance
            Equations (4) and (5) are derived from equations (1–3)   (quality) of the vascular configurations:
           which enable the calculation of the length and the radius
           of each vessel in the vascular system, respectively:                                                                                    (8)
                                                               where     is the volume of the skin model occupied
                                                               by living cells while is    the total volume of the skin
                                                              (4)  model. The total volume is composed of the volume
                                                               occupied by the blood vessel system (i.e. there is a
                                                               “penalty” for the performance if a complex (i.e. large)

                                                        (5)    vessel system is used), the volume of the substrate
                                                               which is sufficiently supplied by nutrients, and the
                                                               volume     which does not provide enough nutrients
                                                               to the cells in order to survive. The threshold glucose
            As the main function of the artificial vascular    concentration    which needs to be reached to supply
           network is supplying the tissue and cells with nutrients   cells adequately was set to    = 2.2 mM. Below this
           and removing metabolic products nutrient diffusion   concentration, severe symptoms of hypoglycaemia occur.
           performance into the area between vessels is a      Finite difference method was used to solve the equation
           determining design factor. Fick’s law and Michaelis-  (6). In this work, we obtained a diagram illustrating the
           Menten kinetics were applied to investigate the nutrient   relationship between performance  and the penetration
           diffusion and cell consumption performance of the   depth   for different levels of vascular vessels, shown
           proposed configuration with different branching levels,  in Figure 3.




           4                           International Journal of Bioprinting (2018)–Volume 4, Issue 2
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