Bone healing response to an injectable calcium phosphate cement with enhanced radiopacity.

The aim of this study was to determine the impact of barium sulfate on remodeling and regeneration in standard tibial defects in rabbits treated with the Norian skeletal repair system (SRS). Two formulations of SRS (with and without barium sulfate) were injected into the medullary canal of the tibia of New Zealand white rabbits. Animals were sacrificed at 6 weeks, 6 months, 1 year, and 2 years. Over the 2-year duration of the study, standard SRS and SRS with barium sulfate appeared to be biocompatible and osteoconductive with no evidence of either inflammation or fibrous tissue around the implant materials or at the bone-material interfaces. This outcome underscores the osteophilic property of the SRS. A difference we observed between the standard SRS and the SRS with barium sulfate was the appearance of acellular material contiguous to the SRS with barium sulfate. Energy dispersive X-ray spectroscopy (EDX) analysis was conducted and confirmed that the acellular material was barium sulfate. Pathological examination of additional tissues including regional lymph nodes revealed neither dissemination of calcium phosphate nor barium sulfate. We concluded that the residual barium sulfate detected by EDX was localized to the intramedullary canal of the tibia.

Noggin underexpression and runx-2 overexpression in a craniosynostosis rabbit model.

INTRODUCTION: Normal suture fusion has been shown to be driven by the molecular signals elucidated by the underlying dura. However, the pathogenesis of suture fusion in craniosynostosis is not well described. The purpose of our study was to examine the expression patterns of 2 important molecular signals (Noggin and Runx-2) in a cohort of congenital craniosynostotic rabbits to gain a better understanding of suture behavior in craniosynostosis. METHODS: Coronal (fusing) and sagittal (patent) rabbit cranial sutures from a colony of congenitally synostosed rabbits and wild-type (control) rabbits were harvested at a neonatal time point. These sections were then grown in organ culture and harvested for histology at 0, 7, or 14 days of culture. Fusion percentage was then assessed and an overall fusion score was calculated. Expression of Noggin and Runx-2 was then localized by immunohistochemistry and quantified by Western blot analysis. RESULTS: Histology of the wild-type cranial sutures (control) showed suture patency (score of 0%) for all coronal and sagittal sutures at 0 days, 7 days, and 14 days of organ culture. Sagittal sutures of craniosynostotic animals also showed suture patency (score of 0%) at all culture times (0, 7, and 14 days). Of the 18 coronal sutures from the craniosynostotic animals, 8 remained patent and 10 fused. For the coronal sutures that fused, fusion scores of 14%, 41%, and 84% were documented at 0, 7, and 14 days of organ culture, respectively. With immunolocalization, Noggin was found to be expressed in both the dura and suture cells underlying patent sutures, but not in fusing sutures in vitro. Runx-2 was found to be expressed in the dura beneath the suture and suture cells of fusing sutures, not patent sutures. Western blot densitometry confirmed these findings. CONCLUSIONS: Our results suggest that pathologic rabbit coronal sutures progressed toward complete suture fusion in vitro, and expression patterns of Noggin and Runx-2 paralleled that of a well-studied normal suture fusion model.

Rescue of coronal suture fusion using transforming growth factor-beta 3 (Tgf-beta 3) in rabbits with delayed-onset craniosynostosis.

Craniosynostosis results in cranial deformities and increased intracranial pressure, which pose extensive and recurrent surgical management problems. Developmental studies in rodents have shown that low levels of transforming growth factor-beta 3 (Tgf-beta 3) are associated with normal fusion of the interfrontal (IF) suture, and that Tgf-beta 3 prevents IF suture fusion in a dose-dependent fashion. The present study was designed to test the hypothesis that Tgf-beta 3 can also prevent or "rescue" fusing sutures in a rabbit model with familial craniosynostosis. One hundred coronal sutures from 50 rabbits with delayed-onset, coronal suture synostosis were examined in the present study. The rabbits were divided into five groups of 10 rabbits each: 1) sham controls, 2) bovine serum albumin (BSA, 500 ng) low-dose protein controls, 3) low-dose Tgf-beta 3 (500 ng), 4) high-dose BSA (1,000 ng) controls, and 5) high-dose Tgf-beta 3 (1,000 ng). At 10 days of age, radiopaque amalgam markers were implanted in all of the rabbits on either side of the coronal suture to monitor sutural growth. At 25 days of age, the BSA or Tgf-beta 3 was combined with a slow-absorbing collagen vehicle and injected subperiosteally above the coronal suture. Radiographic results revealed that high-dose Tgf-beta 3 rabbits had significantly greater (P < 0.05) coronal suture marker separation than the other groups. Histomorphometric analysis revealed that high-dose Tgf-beta 3 rabbits also had patent coronal sutures and significantly (P < 0.01) greater sutural widths and areas than the other groups. The results suggest that there is a dose-dependent effect of TGF-beta 3 on suture morphology and area in these rabbits, and that the manipulation of such growth factors may have clinical applications in the treatment of craniosynostosis.