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International Journal of Bioprinting                                  3D bioprinting of composite hydrogels









































            Figure 5. Transparency of (a) GG hydrogel bioinks, (b) 2.5GG–PEI hydrogel bioinks, and (c) 3D bioprinted 2.5GG–PEI composite hydrogels in water at
            room temperature. Water was used as the control; n = 4 for each sample. Abbreviations: CA, citric acid; GG, gellan gum; PEI, polyethyleneimine.


            with higher gel content and higher crosslinking density   where Q  is the cumulative amount of released drug at
                                                                        t
            leading to slower degradation.  The slow degradation of   time t, Q  is the initial amount of drug, and k and t denote
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                                                                      0
            GG is likely due to the complete and efficient crosslinking   first-order constant and time, respectively. The scaffold
            in the presence of CA, which electrostatically interacts   displayed a burst release within the first 8 h, and the drug
            with OH groups in GG through its COO functional    release became constant after about 24 h. The drug release
            groups. With the addition of PEI, the negatively charged   reached approximately 63% ± 2.19% and 65.3% ± 2.39%
            COO groups interact with positively charged NH groups,   at 8 and 24 h, respectively. Various factors influence the
            thereby reducing the crosslinking density and accordingly   release process of an encapsulated drug from a hydrogel,
            increasing the degradation rate. Despite the increase in the   including the hydrogel structure, crosslinking density,
            degradation rate of GG in the presence of PEI, the high cell   solubility of the encapsulated drug, the composition of
            affinity of PEI could provide a desirable platform for cell   the hydrogel, and interactions between the drug and the
            growth, adhesion, and proliferation.               hydrogel. According to the release behavior of BSP, it can be
                                                               concluded that after immersing the BSP-loaded scaffold in
            3.6. Drug release                                  PBS, ion exchange occurred, and the ionic bonds between
            Figure 7 displays the BSP release from the 3D-bioprinted   the phosphate groups of BSP and the amine groups of the
            GG–3PEI scaffold after immersion in PBS. Data were   scaffold were disrupted, resulting in a burst release. After
            fitted with mathematical drug release models, including   8 h, ionic equilibrium was achieved, resulting in slow and
            zero order, first order, Higuchi, Korsmeyer–Peppas, and   sustained drug release. Burst release, in particular within
            Hixon–Crowell. The correlation coefficient (R ) values   the first hours, can accelerate the action of the drug to
                                                   2
            strongly suggest that the drug was released according to   combat acute inflammation. For BSP delivered in eye
            first-order kinetics (R  = 0.976). The release profile of the   drops, the drug is released instantaneously with rapidly
                             2
            sample was modeled by Equation IV.                 diminishing effects, requiring reapplication every 2 h.
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                                                               Conversely, the 3D-bioprinted scaffold system enables
                          Q  = k ln t + Q 0            (IV)    controlled and prolonged release of BSP.
                           t
            Volume 10 Issue 4 (2024)                       329                                doi: 10.36922/ijb.3440
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