title: Histological assessment of bioengineered new bone in repairing osteoperiosteal mandibular defects in sheep using recombinant human bone morphogenetic protein-7.
abstract: 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.
  
  
  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 microm/day (range 0.62-5.63 microm/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.
authors.affiliation: Biotechnology and Craniofacial Section (BACS), Glasgow Dental Hospital and School, Glasgow University, Regional Maxillofacial Surgery Unit, Southern General Hospital, Glasgow, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Abu-Serriah
authors.forename: E
authors.initials: E
authors.lastname: Odell
authors.forename: C
authors.initials: C
authors.lastname: Lock
authors.forename: A
authors.initials: A
authors.lastname: Gillar
authors.forename: A F
authors.initials: AF
authors.lastname: Ayoub
authors.forename: R H
authors.initials: RH
authors.lastname: Fleming
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D001860:Bone Plates; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D005260:Female; D008334:Mandible / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008856:Microscopy, Fluorescence; D011994:Recombinant Proteins / Q000627:therapeutic use; D012756:Sheep; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta