Histological assessment of bioengineered new bone in repairing osteoperiosteal mandibular defects in sheep using recombinant human bone morphogenetic protein-7

• Published in: British journal of oral & maxillofacial surgery 2004-10, Vol.42 (5), p.410-418
• Main Authors: Abu-Serriah, M.M., Odell, E., Lock, C., Gillar, A., Ayoub, A.F., Fleming, R.H.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; BMP; Bone bioengineering; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins - therapeutic use; Bone Plates; Bone Regeneration - drug effects; Bone Regeneration - physiology; Dentistry; Female; Mandible - anatomy & histology; Mandible - drug effects; Mandible - physiology; Mandibular reconstruction; Medical sciences; Microscopy, Fluorescence; Osteoinduction; Otorhinolaryngology. Stomatology; Recombinant Proteins - therapeutic use; Sheep; Transforming Growth Factor beta - therapeutic use
• ISSN: 0266-4356; 1532-1940
• DOI: 10.1016/j.bjoms.2004.05.005

Numerous experimental studies have been published about osteoinductive bone morphogenetic proteins (BMPs). However, to our knowledge there has been no detailed histological study of a mandibular defect in a large mammal, reconstructed using BMPs. We describe here the histological features of rhBMP-7-induced bone in mandibular defects in sheep. Methods: A 35 mm osteoperiosteal defect was created at the parasymphyseal region of the mandible in six adult sheep. The continuity of the mandible was maintained using a bony plate, and rhBMP-7 was applied on a type I collagen carrier. Bone labels were injected at selected time intervals during the follow-up period. The animals were killed after 3 months and bone samples were examined histologically, histomorphometrically, and by fluorescence microscopy. Results and conclusions: We found a mixture of woven and lamellar bone that contained many cells with large nuclei. This had not reorganised to form cortical bone and the rhBMP-7-induced bone was more porous than the native bone. The newly-formed bone restored both endosteal and periosteal layers. rhBMP-7-induced bone was biocompatible and induced no ossification of soft tissue or abnormal growth of nearby vital structures. The mineral apposition rate was 1.98 μm/day (range 0.62–5.63 μm/day), a value close to that reported in humans. This suggests that BMPs have a limited effect in accelerating the rate of mineralisation, but promote the pre-mineralisation processes, and perhaps the formation of woven bone.