Rapid re-synostosis following suturectomy in pediatric mice is age and location dependent

Abstract

Craniosynostosis is the premature fusion of the cranial sutures early in development. If left untreated, craniosynostosis can lead to complications resulting from cranial deformities or increased intracranial pressure. The standard treatment involves calvarial reconstruction, which in many cases undergoes rapid re-synostosis. This requires additional surgical intervention that is associated with a high incidence of life threatening complications. To better understand this rapid healing, a pediatric mouse model of re-synostosis was developed and characterized. Defects (1.5mm by 2.5mm) over the posterior frontal suture were created surgically in weanling (21 days post-natal) and adolescent (50 days post-natal) C57Bl/6J mice. In addition, defects were created in the frontal bone lateral to the posterior frontal suture. The regeneration of bone in the defect was assessed using advanced image processing algorithms on micro-computed tomography scans. The genes associated with defect healing were assessed by real-time PCR of mRNA isolated from the tissue present in the defect. The results showed that the weanling mouse healed in a biphasic process with bone bridging the defect by post-operative (post-op) day 3 followed by an increase in the bone volume on day 14. In adolescent mice, there was a delay in bone bridging across the defect, and no subsequent increase in bone volume. No bridging of the defect by 14 days post-op was seen in identically sized defects placed lateral to the suture in both weanling and adolescent animals. This study demonstrates that bone regeneration in the cranium is both age and location dependent. Rapid and robust bone regeneration only occurred when the defect was created over the posterior frontal suture in immature weanling mice.