Effect of recombinant human bone morphogenetic protein-4 with carriers in rat calvarial defects.
BACKGROUND
Bone morphogenetic proteins (BMPs) are being evaluated as candidates for periodontal and bone regenerative therapy. However, the research on recombinant human bone morphogenetic protein-4 (rhBMP-4) has been insufficient to evaluate its capacity to enhance bone formation and its carrier system. The purpose of this study was to evaluate the bone regenerative effect of rhBMP-4 delivered with an absorbable collagen sponge (ACS) or beta-tricalcium phosphate (beta-TCP). We also compared the potential of beta-TCP to that of ACS as a carrier system for rhBMP-4.


METHODS
Eight-mm calvarial critical-sized defects were created in 100 male Sprague-Dawley rats. The animals were divided into 5 groups of 20 animals each. The defects were treated with rhBMP-4/ACS (rhBMP-4 at 0.05 mg/ml), rhBMP-4/beta-TCP (rhBMP-4 at 0.05 mg/ml), ACS alone, beta-TCP alone, or left untreated for surgical control. The rats were sacrificed at 2 or 8 weeks postsurgery, and the results were evaluated radiodensitometrically, histologically, and histomorphometrically.


RESULTS
The results of radiodensitometric analysis were as follows: the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups were more radiopaque than other groups at both 2 and 8 weeks (P < 0.01). The histologic observations were as follows: in the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups, new bone was evident at the defect sites at 2 weeks and 8 weeks. The results of histomorphometric analysis were as follows: the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups had more bone (%) than other groups at both 2 and 8 weeks (P < 0.01).


CONCLUSIONS
Surgical implantation of rhBMP-4/ACS may be used to support bone regeneration in the rat calvarial critical-sized defect, and rhBMP-4/beta-TCP may be able to regenerate bone in the rat calvarial critical-sized defect without complication. In addition, both ACS and beta-TCP may be considered as available carriers for rhBMP-4.
Ahn
Seong-Hee
SH
Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Korea.
Kim
Chang-Sung
CS
Suk
Hun-Joo
HJ
Lee
Yong-Jun
YJ
Choi
Seong-Ho
SH
Chai
Jung-Kiu
JK
Kim
Chong-Kwan
CK
Han
Soo-Boo
SB
Cho
Kyoo-Sung
KS
D015502:Absorptiometry, Photon; D000818:Animals; D001672:Biocompatible Materials; D015519:Bone Density / Q000187:drug effects; D001847:Bone Diseases / Q000188:drug therapy* / Q000473:pathology; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates; D004337:Drug Carriers; D005781:Gelatin Sponge, Absorbable; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012886:Skull / Q000187:drug effects* / Q000473:pathology
C525809:BMP4 protein, human; D001672:Biocompatible Materials; C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D004337:Drug Carriers; D011994:Recombinant Proteins; C485817:beta-tricalcium phosphate; C018392:tricalcium phosphate