Targeting of C-ROS-1 Activity Using a Controlled Release Carrier to Treat Craniosynostosis in a Preclinical Model of Saethre-Chotzen Syndrome

Figure 3

Local administration of CollaCote fragments infused with crizotinib reduces coronal suture fusion in 20-day-old mice. (a) Representative μCT images of coronal sutures (arrows) of 20-day-old mouse skulls following local implantation of CollaCote sponge carriers containing either 0.1% DMSO or crizotinib at different concentrations (1-4 μM) at P8. (b) Representative images of Masson’s trichome-stained coronal sutures (white arrow: closed sutures, black arrow: open sutures) of 20-day-old mice following local implantation of CollaCote sponge carriers containing either 0.1% DMSO or 4 μM crizotinib at P8, scale bar = 100 μm (100×). (c) Number of open coronal sutures versus closed coronal sutures in crizotinib-treated mice at P20 (n = 12 per the treatment group). (d) Histomorphometric analysis of mineralized bone formed of locally treated coronal sutures. Values are the mean ± SEM, , one-way ANOVA with Tukey’s multiple comparisons, DF = 3, F = 2.623 (1 μM Crizo, ; 2 μM Crizo, ; 4 μM Crizo, ), n = 9–21 coronal sutures/treatment group. (e) Histomorphometric analysis of bone volume fraction (bone volume/total volume) of locally treated coronal sutures. Values are the mean ± SEM, , one-way ANOVA with Tukey’s multiple comparisons, DF = 3, F = 4.193 (1 μM Crizo, ; 2 μM Crizo, ; 4 μM Crizo, ), n = 9–17 coronal sutures/treatment group.

(a)

(b)

(c)

(d)

(e)