Bone morphogenic protein-2 gene therapy for mandibular distraction osteogenesis.
Distraction osteogenesis (DO) requires a long consolidation period and has a low but real failure rate. Bone morphogenic proteins (BMPs) accelerate bone deposition in fractures and critical-sized bone defects, but their effects on mandibular DO are unknown. We investigated the effect of local delivery of adenovirus containing the gene for BMP-2 (Adbmp-2) on mandibular DO in a rat model. Rats (n = 54) were distracted to 3 mm over 6 days. At the start of consolidation (POD 10), Adbmp-2 or adenovirus containing the lacZgene (AdlacZ) was injected directly into the distraction zone. After 1, 2, and 4 weeks of consolidation, mandibles were evaluated for amount of bone deposition. Adbmp-2-treated specimens demonstrated an increased amount of new bone formation by radiographic, histologic, and histomorphometric analysis. This study demonstrates that local, adenovirally-mediated delivery of BMP-2 can increase bone deposition during DO, potentially shortening consolidation and enhancing DO in poorly healing mandibles, such as occurs postirradiation.
Ashinoff
Russell L
RL
Laboratory of Microvascular Research and Vascular Tissue Engineering, Institute for Reconstructive Plastic Surgery, New York University Medical Center, New York, NY, USA.
Cetrulo
Curtis L
CL
Galiano
Robert D
RD
Dobryansky
Michael
M
Bhatt
Kirit A
KA
Ceradini
Daniel J
DJ
Michaels
Joseph
J
McCarthy
Joseph G
JG
Gurtner
Geoffrey C
GC
D000256:Adenoviridae; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D015316:Genetic Therapy / Q000379:methods*; D015151:Immunoblotting; D008297:Male; D008334:Mandible / Q000601:surgery*; D019857:Osteogenesis, Distraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta