Synergistic Effect of BMP2 with Bone Grafts Covered by FGF2 Soaked Collagen Membrane on New Bone Formation in Mongrel Dogs

Abstract

Purpose: The purpose of this study is to evaluate, through histomorphometric analysis, synergistic effect of sequential use of both BMP2 and FGF2 on new bone formation by using BMP2 with Biphasic Calcium Phosphate (BCP) covered by FGF2 soaked collagen membrane in the maxillary lateral augmentation defect model of Mongrel dog. Methods: Six male mongrel dogs were used in this study. All maxillary premolars (P1, P2, P3) were extracted bilaterally and 8 weeks after extraction, box-shaped lateral defects with dimension of 5 mm x 5 mm x 5 mm3 were surgically created. Then, the defects were filled with BCP containing BMP2 and covered by either collagen membranes soaked with saline (BMP2 group) or collagen membranes soaked with FGF2 (BMP2+FGF2 group). 4 and 12 weeks following treatment, dogs were sacrificed and histological and histomorphometric analyses were performed. Results: Histological analysis revealed that a greater amount of newly-formed immature bone was observed in BMP2+FGF2 group than that of BMP2 group. In histomorphometric analysis, at 4 weeks post-treatment, BMP2 group showed greater amount of new bone formation (23.04±4.67%), connective tissue volume (24.06±7.73%), and osteoclast number (76.86±36.76 unit), than those of BMP2+FGF2 group; (21.03±8.80%), (23.36±6.27%), and (76.17±22.61 unit), respectively. Furthermore, BMP-2 group showed a smaller amount of the graft material remained (15.21±7.44%), and blood vessel count (95.33±22.46 unit), than those of BMP2+FGF2 group; (19.60±6.82%) and (106.33±29.17 unit), respectively. In contrast, at 12 weeks post-treatment, BMP2+FGF2 group showed a greater amount of new bone formation (35.55±8.35%), connective tissue volume (12.48±3.32%), blood vessel count (64.83±8.80 unit) and number of osteoclast (123.17±49.93 unit) than those of BMP2 group; (30.12±8.25%), (17.02±8.15%), (47.33±15.59 unit), and (103.00±39.14 unit), respectively. However, BMP2+FGF2 group showed a smaller amount of the graft material remained (3.11±2.80%) than BMP2 group (8.76±4.16%). Conclusions: Within the limitation of this study, while their short-term effect is limited, the delivery of both BMP2 and FGF2 may have long-term synergistic effect on new bone formation and therefore, may supply a promising treatment modality for repairing large bone defects.

Key words: Guided bone regeneration ( GBR ), Biphasic Calcium Phosphate ( BCP ), Bone morphogenetic proteins 2 ( BMP2 ), Fibroblast growth factor 2( FGF2 ).