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International Journal of Bioprinting                         Dual ions mixed GelMA for hair follicle regeneration







































            Figure 3. The proangiogenic effect of different concentrations of ions. (A) The typical images of tube formation of HUVECs with different treatments.
            (B, C) Quantitative analysis of tube formation ability. *P < 0.05, **P < 0.01, ***P < 0.001. N = 3 for each group. All the analyses were performed with one-
            way ANOVA. Scale bar = 200 μm.

            pure GelMA hydrogel, GelMA-Zn/Si hydrogel showed no   compared to pure GelMA and is still suitable for treatment
            great changes in mechanical properties. Figure 4G presents   application.
            typical compressive stress-strain curves of different
            hydrogels. The two curves almost coincide, and there is   3.5. Wound healing and regeneration of hair follicle
            no  difference  in  compressive  modulus  between  the  two   in mice models
            hydrogels (Figure 4H).                             To  determine  whether  ions  promote  in situ  hair  follicle

               The rheological properties of both hydrogels were   regeneration  in vivo,  we  introduced  a  mouse  excisional
            investigated by frequency sweeping. Storage modulus (G′)   model. As shown in  Figure 5, there was no significant
            and loss modulus (G″) of hydrogels were tested by time   difference between the two groups on day 0 in the wound
            scanning.  Figure 4I indicates that GelMA and GelMA-  area. On day 7, the wound area of the control group
            Zn/Si hydrogels have an identical point where G′ and   greatly decreased, possibly due to the contraction of the
            G″ intersected with each other.  The viscosities of both   wound without moisturizing, but the group showed more
            hydrogels have the same tendency with the increasing shear   significant  scar  formation.  At  the  time-point,  we  found
            rate (Figure 4J). Frequency scanning reveals that the value   that the GelMA-Zn/Si group had moister and smoother
            of G′ is higher than that of G″ within an angular frequency   wounds without scar formation than other groups. Pure
            range of 0.1–100 rad/s (Figure 4K). The ion release    GelMA group also had relatively good wounds, which were
            behavior of GelMA-Zn/Si hydrogel was evaluated by ICP.   better than hydrocolloid group. On day 14, all the treated
            The results showed that the cumulative release of Zn and Si   groups almost achieved closure, while the control group
            ions reached 0.363 μg/mL and 0.060 μg/mL, respectively, in   still presented with detectable unhealed wounds. More
            7 days (Figure 4L). For that, 1 mL GelMA-Zn/Si hydrogel   interestingly, the GelMA-Zn/Si group had more significant
            was soaked in 9 mL PBS, the ion concentration was within   hair follicle reappearance in the center of the wound and
            biologically active concentration range after conversion.   less scar formation based on gross observation, which
            Taken together, our results suggest that GelMA-Zn/Si   indicates that GelMA-Zn/Si hydrogel can promote in situ
            hydrogel has  no changes  in physicochemical properties   hair follicle regeneration and reduce scar formation.


            Volume 9 Issue 3 (2023)                        206                          https://doi.org/10.18063/ijb.703
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