Effect of recombinant human bone morphogenetic protein-4 dose on bone formation in a rat calvarial defect model.
BACKGROUND
Bone morphogenetic proteins (BMPs) are being evaluated for periodontal and bone regenerative therapy. The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-4 (rhBMP-4) dose on local bone formation in a rat calvaria defect model.


METHODS
Calvarial, 8 mm diameter, critical-size osteotomy defects were created in 140 male Sprague-Dawley rats. Seven groups of 20 animals each received either 1) rhBMP-4 (2.5 microg) in an absorbable collagen sponge (ACS) carrier, 2) rhBMP-4 (5 microg)/ACS, 3) rhBMP-4 (2.5 microg) in a beta-tricalcium phosphate (beta-TCP) carrier, 4) rhBMP-4 (5 microg)/beta-TCP, 5) ACS or 6) beta-TCP carrier controls, or 7) a sham-surgery control, and were evaluated by histologic and histometric parameters following a 2- or 8-week healing interval (10 animals/group/healing interval).


RESULTS
Surgical implantation of rhBMP-4/ACS and rhBMP-4/beta-TCP resulted in enhanced local bone formation at both 2 and 8 weeks. Within the dose range examined, rhBMP-4 did not exhibit an appreciable dose-dependent response. Defect closure was not significantly different between the rhBMP-4/ACS and rhBMP-4/beta-TCP groups. New bone area of the rhBMP-4/ beta-TCP group was significantly greater than that of the rhBMP-4/ ACS group; however, bone density in the rhBMP-4/ACS group was significantly greater than that in the rhBMP-4/beta-TCP group at 8 weeks (P < 0.05).


CONCLUSIONS
rhBMP-4 combined with ACS or beta-TCP has a significant potential to induce bone formation in the rat calvaria defect model. Within the selected rhBMP-4 dose range and observation interval, there appeared to be no meaningful differences in bone formation.
Pang
Eun-Kyoung
EK
Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Korea.
Im
Se-Ung
SU
Kim
Chang-Sung
CS
Choi
Seong-Ho
SH
Chai
Jung-Kiu
JK
Kim
Chong-Kwan
CK
Han
Soo-Boo
SB
Cho
Kyoo-Sung
KS
D000818:Animals; D001672:Biocompatible Materials; D001847:Bone Diseases / Q000473:pathology / Q000601:surgery*; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D002130:Calcium Phosphates; D003094:Collagen; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005781:Gelatin Sponge, Absorbable; D006801:Humans; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012886:Skull / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
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; D003094:Collagen