Murine Rapid Re-synostosis Model is Both Location and Age Dependent

Objectives: Craniosynostosis is the premature fusion of the cranial sutures and commonly requires complex calvarial reconstruction. In up to 40% of cases, the bones re-fuse resulting in re-synostosis that requires subsequent surgical intervention associated with a high incidence of serious complications. The objective of this study was to determine if the regenerative ability of a murine cranial defect varies with age and location.

Methods: Under approval of the GA Tech IACUC, a 1.5 by 2.5 mm calvarial defect was created in C57Bl/6J mice removing the posterior frontal suture or a bone region lateral to the suture. The surgery was performed on either post-natal day 21 or 50 for the juvenile or adult groups, respectively. On post-operative days 2, 5, and 14, five mice were randomized into each group for imaging with micro-CT and histology. The mean defect distance and bone volume in the defect was quantified using our novel snake algorithm previously validated with serial histology. A P<0.05 was considered statistically significant by ANOVA and Bonferroni post-test.

Results: The defects over the juvenile suture had a significant decrease in defect distance by 5 days post-op followed by an increase in bone volume by 14 days post-op. The adult suture group had a decrease in defect distance later at 14 days post-op while there was no increase in bone volume. None of the bone defects lateral to the suture showed any decrease in distance by 14 days post-op; however the bone volume adjacent to the edges of defect increased for the juvenile group only.

Conclusion: Our algorithm shows that the rapid re-synostosis in a murine model is both location and age dependent. All the defects created over the posterior frontal suture went on to nearly complete bridging while any increase in bone volume was specific to the juvenile animals.