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Shpichka, et al.
           2.4 Mechanical properties                           dependent  on  the  polymerization  conditions,
                                                               including a concentration of fibrinogen, thrombin,
           Pure fibrinogen solutions show a nonlinear increase   additional factors such as Factor XIII and CaCl , and
           in viscosity with increasing concentration,  with   physical factors such as temperature and external
                                                                                                         2
           the values ranging from ones to hundreds of cP .    tension or compression forces. Several models for
                                                        [19]
           Moreover, the concentration of the fibrinogen in    fibrin  mechanics  have  been  suggested  that  take
           blood plasma correlates with plasma viscosity .     into account its filamentous nature and interactions
                                                        [20]
           The  drastic  changes  in  mechanical  properties   between the fibers at different hierarchy levels [7,8,17] .
           occur with the onset of the fibrin clot formation     The storage modulus of the gel only weakly
           (gelation), which could be traced by a change of    depends on frequency, while the loss modulus
           turbidity  and an increase in the elastic or shear   increases with frequency  [23] .  Thus,  at  low
                   [21]
           modulus in rheological  measurements   [22-24] .  In   frequencies  (<10  –  100  Hz),  the  behavior
           vitro, gelation time which can take from several    is  mostly  elastic  and  could  be  efficiently
           seconds to several minutes is mostly controlled by   characterized  by  elastic  modulus  only,  but
           the concentration of thrombin and temperature [21,25] .  the viscous component is pronounced at high
             The resulted fibrin gel has a set of remarkable   frequencies. The shear and elastic moduli show
           and unique viscoelastic properties among polymers   non-linear behavior with relation to strains, the
           which are related to its molecular structure with   so-called strain hardening or stiffening [23] . Shear
           complex multi-scale hierarchy .  Fibrin  fibers     modulus increases up to a factor of twenty-
                                          [7]
           might constitute <1% of the gel volume, yet it will   fold at large strains [18] .  The  elastic  modulus
           have  measurable  elastic  modulus  and  strength.   initially  decreases  (up  to  strain  =  0.5),  but
           The gel also has a high water-uptake ratio of 30 –   then dramatically increases by a factor of 100
           50 . The fibrin fibers of the gel can have different   (compressive strains >0.8) [26] . Strain hardening
             [21]
           length, thickness, and density and type of branching   might be of biological importance since it
           points,  which  generally  made  up  of  three  fibers   allows fibrin clots to sustain larger deformations
           at  a  junction [17,23] .  These  parameters  are  strongly   without significant integrity loss.

           Table 1. Mechanical properties of pure fibrinogen and fibrin.

            Components concentrations                           Viscosity   E(Pa)    G’ (Pa)   Comments   Ref
            Fibrin   Thrombin   Ca+   Factor XIII     Buffer       (cP)
            (mg/ml)   (U/ml)   (mM)     (µg/ml)
           10–150        –       –         –           PBS        2–43      n/a        n/a         –      [19]
           25           100      –         –           PBS         n/a    580-640      –           –      [27]
           1, 2, 4, 8  0.1–6.4   –         –            –          n/a      n/a     3.1-247.5      –      [28]
           6, 7, 8, 9    –       –         –            –          n/a      n/a       4-147    PEGylated  [29]
                                                                                               fibrinogen,
                                                                                               polymerized
                                                                                                by photo-
                                                                                                initiator
                                                                                               using a UV
                                                                                                  light
           2–50        2–100     40        –            –          n/a     0.058–      n/a         –      [39]
                                                                           4000
           2             1       2       0–20        HEPES         n/a      n/a      33-150        –       [6]
                                                      23 mM
                                                      NaCl
                                                  175 mM pH 7.4
           Ref.: References; E: Young’s modulus; n/a: Not available; PBS: Phosphate buffer saline; HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
                                       International Journal of Bioprinting (2020)–Volume 6, Issue 3        29
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