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International Journal of Bioprinting                                          Core-shell bioarchitectures













































            Figure 3. In silico results. (A) Predicted average degree of gelation (α) as a function of shell alginate viscosity (for 1 mg/mL Pluronic in the core) after
                    2+
                                                                                            2+
            15 min in Ca  medium crosslinking. (B) Predicted average α as a function of core Pluronic concentration after 15 min in Ca  crosslinking (*p < 0.05).
            (C) Computational simulation of alginate shell formation as a function of crosslinking time (for 20 mg/mL alginate in the shell and 1 mg/mL Pluronic in
            the core). (D) Comparison of experimental shell thickness (black dotted line) and computational values, for the same condition in C, estimated with (blue
            line) and without (orange line) accounting for the Brinkman coefficient b.
            3. Results                                         crosslinking time for all the experiments. As an example,
                                                               for the condition shown in  Figure 3C, the average
            3.1. In silico results                             alginate concentration in the shell (C ) = 0.47 mol/m ,
                                                                                                            3
            The reaction diffusion models show that the degree of   corresponding to α = 0.68 (see Section S5 in Supplementary
                                                                                              gel
            gelation in the shell (α) increases as a function of alginate   File).
            viscosity  (and  hence  concentration),  up  to  a  viscosity
            corresponding to that of 20 mg/mL alginate. After this   In addition, our computations showed that after
            point,  α decreases with increasing alginate viscosity   15 min under the crosslinking process, the Ca  diffusion
                                                                                                    2+
            because  Ca   ion  diffusion  is  inhibited   (Figure  3A).   time within the alginate network is lower than that of un-
                     2+
                                             [36]
            Moreover, Figure 3B shows that the presence of Pluronic in   crosslinked alginate and Pluronic (see  Section S3 and
            the core significantly increases α (0.63 ± 0.06 for 1 mg/mL    Table S5 in Supplementary File). This suggests that alginate
            Pluronic, 0.71 ± 0.03 for 10 mg/mL Pluronic) with respect   crosslinking occurs before core and shell material become
            to a water core (0.4 ± 0.03, p < 0.05). However, no significant   a continuum and thus the bead structure is conserved.
            differences in the degree of gelation were observed
            between the two Pluronic concentrations investigated. A   Finally,  Figure 3D shows that the shell thicknesses
            crosslinking degree of α = 0.6 corresponding to complete   estimated considering the hindered diffusion were
            alginate gelation at the end of the crosslinking kinetics   more similar to the experimental data with respect to
            in the alginate shell occurred within 15 min in all the   the computational data derived without considering
            conditions [30,31] . Thus, this time was selected as optimal   Brinkmann’s coefficient  b. This demonstrates that the


            Volume 9 Issue 5 (2023)                        438                          https://doi.org/10.18063/ijb.771
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