Paracrine effect of the bone morphogeneticprotein-2 at the experimental site on healing of the adjacent control site: a study in the rabbit calvarial defect model

Abstract

Purpose: The aim of this study was to assess the possible paracrine effect of bone morphogeneticprotein-2 (BMP-2) at the experimental site on the adjacent control site for validating a rabbit calvarial defect model as a means of verifying the effect of BMP-2.

Methods: Sixteen rabbits were divided into two groups (n=8 in each) according to whether or not BMP-2 would be used. Two circular defects (8 mm in diameter) were created side by side, 2 mm apart, in the calvarium of all of the rabbits. In each animal, one of the defects was grafted with either BMP-2-loaded carrier or carrier material alone. The control defects adjacent to these grafted defects, designated CB (the nongrafted defect adjacent BMP-2-loaded carrier-grafted defect) and CC (the nongrafted defect adjacent to carrier only-grafted defect), respectively, were the focus of this study, and were filled only with a blood clot in all of the animals. Histologic observation and histomorphometric analysis were performed at 2 and 8 weeks (n=4 animals per point in time) after surgery.

Results: There was no noteworthy difference in the healing pattern, and no statistically significant differences in histomorphometric parameters such as the defect closure, new bone area, or total augmented area between the CC and CB groups.

Conclusions: The results of this study suggest that rabbit calvarial defects separated by a distance of 2 mm are suitable for evaluating the effects of BMP-2 and the control defect can be regarded not to be affected by BMP-2 applied defect.

Keywords: Animal experimentation; Bone morphogenetic protein 2; Bone regeneration; Research design.

Figure 1

Clinical photograph of the experiment. Two 8-mm diameter defects were made, 2 mm apart, in the calvaria of 16 rabbits.

Figure 2

Schematic diagram of a calvarial defect showing the parameters that were analyzed histomorphometrically. The calculations for various measurements are shown.

Figure 3

Representative photomicrographs obtained at 2 weeks postoperatively: the CC group (A) and the CB group (B) (A, B: H&E, ×40). CC: control defect adjacent to a defect grafted with biphasic calcium phosphate carrier only, CB: control defect adjacent to a defect grafted with biphasic calcium phosphate carrier loaded with bone morphogenetic protein-2.

Figure 4

Representative photomicrographs obtained at 8 weeks postoperatively: the CC group (A) and the CB group (B) (A, B: H&E, ×40). CC: control defect adjacent to a defect grafted with biphasic calcium phosphate carrier only, CB: control defect adjacent to a defect grafted with biphasic calcium phosphate carrier loaded with bone morphogenetic protein-2.