Recombinant human bone morphogenetic protein-2 suspended in fibrin glue enhances bone formation during distraction osteogenesis in rabbits.
BACKGROUND
Bone morphogenetic protein-2 (BMP-2) has high potential for bone formation, but its in vivo effects are unpredictable due to the short life time. This study was designed to evaluate the effects of recombinant human (rh) BMP-2 suspended in fibrin on bone formation during distraction osteogenesis (DO) in rabbits.


METHODS
The in vitro release kinetics of rhBMP-2 suspended in fibrin was tested using an enzyme-linked immunosorbent assay. Unilateral tibial lengthening for 10 mm was achieved in 48 rabbits. At the completion of osteodistraction, vehicle, fibrin, rhBMP-2 or rhBMP-2 suspended in fibrin (rhBMP-2 + fibrin) was injected into the center of the lengthened gap, with 12 animals in each group. Eight weeks later, the distracted callus was examined by histology, micro-CT and biomechanical testing. Radiographs of the distracted tibiae were taken at both 4 and 8 weeks after drug treatment.


RESULTS
It was found that fibrin prolonged the life span of rhBMP-2 in vitro with sustained release during 17 days. The rhBMP-2 + fibrin treated animals showed the best results in bone mineral density, bone volume fraction, cortical bone thickness by micro-CT evaluation and mechanical properties by the three-point bending test when compared to the other groups (p < 0.05). In histological images, rhBMP-2 + fibrin treatment showed increased callus formation and better gap bridging compared to the other groups.


CONCLUSIONS
The results of this study suggest that fibrin holds promise to be a good carrier of rhBMP-2, and rhBMP-2 suspended in fibrin showed a stronger promoting effect on bone formation during DO in rabbits.
The State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, Sichuan University West China Hospital of Stomatology, Chengdu, China.
Yunfeng
Y
Li
Department of Stomatology, The General Hospital of People's Liberation Army, Beijing, China.
Rui
R
Li
The State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, Sichuan University West China Hospital of Stomatology, Chengdu, China.
Jing
J
Hu
The State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, Sichuan University West China Hospital of Stomatology, Chengdu, China.
Donghui
D
Song
The State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, Sichuan University West China Hospital of Stomatology, Chengdu, China.
Xiaowen
X
Jiang
The State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, Sichuan University West China Hospital of Stomatology, Chengdu, China.
Songsong
S
Zhu
bone formation; bone morphogenic protein-2; distraction osteogenesis; fibrin; release kinetics