BMP2-coprecipitated calcium phosphate granules enhance osteoinductivity of deproteinized bovine bone, and bone formation during critical-sized bone defect healing

Tie Liu,Yuanna Zheng,Yuelian Liu,Gang Wu,Daniel Wismeijer,Janak L Pathak

doi:10.1038/srep41800

Abstract

Most materials used clinically for filling critical-sized bone defects (CSBD), such as deproteinized bovine bone (DBB), lack osteoinductivity so that their therapeutic effects are far from satisfactory. The effect of bone morphogenic protein 2 (BMP2)-coprecipitated biomimetic calcium phosphate granules (BMP2-cop.BioCaP) on osteoinduction of DBB graft(s) during CSBD healing is still unknown. We investigated whether BMP2-cop.BioCaP affects the osteoinductivity of DBB, bone formation, and foreign body reaction during CSBD healing. DBB + BMP2-cop.BioCaP, DBB, DBB + BMP2, DBB + BioCaP, and autologous bone grafts were implanted in the CSBD of sheep. Bone formation, DBB/BioCaP degradability, foreign body reaction, and osteoinductivity of DBB were analyzed histologically and histomorphometrically at week 4 and 8. Combination of BMP2-cop.BioCaP and DBB healed CSBD as effectively as autologous bone grafts. About 95% of the BMP2-cop.BioCaP had been degraded and replaced by new bone at week 8 in the DBB + BMP2-cop.BioCaP-group. Foreign body reaction was reduced in the DBB + BMP2-cop.BioCaP-group compared to the other groups. The independent use of the BMP2-cop.BioCaP did not achieve a satisfactory bone repair. In conclusion, the BMP2-cop.BioCaP showed good degradability and biocompatibility, and enhanced osteoinductivity of DBB during CSBD healing in sheep, suggesting BMP2-cop.BioCaP as a potential osteoinducer to enhance the therapeutic effects of the graft materials in clinic.

Highlights

BMP2-cop.BioCaP granules were visualized by scanning electron microscopy (Fig. 1A,B), and high-resolution electron microscopic image showed that incorporation of BMP2 did not affect the crystalline surface of BioCaP granules (Fig. 1C,D)
We found that BMP2-cop.BioCaP significantly decreased the formation of multinucleated cells on DBB
Due to the limitations related to autografts[4,5,6,7], we propose that BMP2-cop.BioCaP with a biodegradable graft material may be a potent alternative of autologous bone graft to treat the CSBD in the clinic

Summary

Introduction

It has been suggested that combining DBB with a particulate autograft would induce an adequate volume of bone tissue for an excellent restoration. This can provide osteogenic elements[12,18], but the limitations related to autograft remain. The effect of combination of BMP2-cop.BioCaP and DBB on repair of CSBD in large animals had not been investigated. We hypothesized that the BMP2-cop.BioCaP enhances the therapeutic effect of DBB during repair of CSBD. In order to prove this notion we tested the osteoinductivity, degradation, and foreign-body reaction of either BMP2-cop.BioCaP or its combination with DBB in CSBD repair in sheep

Methods

Results

Conclusion