Harnessing the Osteogenic Capability of Neonatal Dura to Heal Critical Sized Defects

While the osteogenic properties of dura are thoroughly documented, the ability of dura to augment critical sized cranial defect (CSD) healing is less established. In the present study we evaluated whether transplanted dura retained sufficient osteogenic potency to aid CSD repair.

Materials and Methods: Craniotomies were performed and 5x5 mm of parietal dura harvested from twenty-four Sprague Dawley rats at 8, 17, and 45 days postnatal. A 2.3 mm CSD was created in the parietal bone of twenty-four 60 day old Sprague Dawley rats. Animals were randomized into four experimental groups: A. 8-day old dura inlayed into CSD; B. 17-day old dura inlayed into CSD; C. 45 day old dura inlayed into CSD; or D. Untreated CSD. Four animals treated with 8-day old dura were evaluated five weeks post-operatively using micro-CT and the remaining animals were evaluated 8 weeks post-operatively with radiographs. Micro-CT images were analyzed for pixel density within the CSD. Radiographic images were evaluated by measuring the distance between new bone formation within the CSD and the edge of the cranial defect; we defined this as the bone gap.

Results: After 5 weeks CSD's treated with 8 day old dura achieved a pixel density essentially equivalent to undisturbed intact cranial bone (p>0.6, Figure 1). Untreated CSD imaged at 5 weeks achieved a pixel density 72% less than undisturbed intact cranial bone;  this difference was extremely significant (p<0.0001). Post operative radiographs of animals at 8 weeks demonstrated defects treated with 8 day old dura had the smallest     bone gap, 7.3 pixels. In contrast, untreated defects or defects treated with 45 day old dura had bone gaps of 37.5 and 36.4 pixels, respectively. The difference between the bone gap of animals treated with 8 day old dura was statistically significant when compared to animals treated with either 17 or 45 day old dura (p<0.05) (Figure 2).

Conclusion: This study suggests that the in vivo osteogenic properties of dura are preserved with transplantation and can be harnessed to augment CSD healing. Future studies will focus on identifying factors responsible for cranial regeneration and engineering biocompatible grafts capable of mimicking dural induced osteogenesis.