Demonstration of the safety of a regenerative bone adhesive for cranial flap fixation in a 12-week clinically relevant sheep model.

OBJECTIVE

Cranial bone flap fixation is typically achieved by using titanium plates and screws (TPS), which are the standard of care. However, the use of hardware to achieve long-term bone fixation and healing across a kerf line poses challenges and potential complications, including infection, nonunion, loosening, cranial flap bone resorption, pain, cosmetic deformity, and CSF leakage. The use of a tetracalcium phosphate and phosphoserine (TTCP-PS) regenerative bone adhesive to fixate cranial flaps has been previously shown to be advantageous compared to TPS in an in vivo ovine model and a human cadaveric model. However, the potential impact of TTCP-PS on the underlying brain has not been previously studied. To investigate the local tissue effects of TTCP-PS bone adhesive compared to TPS, a clinically relevant sheep craniotomy model was developed.

METHODS

Twelve skeletally mature crossbred sheep were used in this study. All craniotomies and surgical procedures were performed by an experienced, US-trained, licensed, and practicing attending neurosurgeon. Bilateral parietal craniotomies were created using a Medtronic Midas Rex craniotome and perforator. Durotomy was performed and repaired in half of the subjects. Craniotomies were repaired with TPS or the TTCP-PS bone adhesive. CT scans were performed postoperatively and at 12 weeks. Histopathology was performed on the brain and cranial bone.

RESULTS

All sheep reached the study endpoint. Histopathological changes in underlying cerebral cortical tissue were comparable in magnitude and incidence between groups (minimal superficial cortical deformation/loss and/or malacia/loss). The magnitude of microgliosis and astrogliosis related to the cortical changes was comparable between groups (minimal/mild and minimal, respectively). Histopathological findings were procedural in nature, associated with the craniotomy model, and unrelated to the bone flap fixation method. The histological changes did not result in clinically adverse effects.

CONCLUSIONS

TTCP-PS was safe, producing no significant difference in adverse effects on local tissues compared to standard craniotomy with plate and screw fixation. This is the first study to quantify histological changes in the underlying cerebral cortex due to standard craniotomy technique.