Animals ; Biomechanical Phenomena ; Bone Diseases/pathology ; Bone Diseases/surgery* ; Bone Marrow/pathology ; Bone Morphogenetic Protein 2/therapeutic use* ; Bone Regeneration/drug effects ; Compressive Strength ; Dogs ; Drug Carriers ; Feasibility Studies ; Female ; Humans ; Internal Fixators ; Osteoblasts/pathology ; Osteogenesis/drug effects ; Osteogenesis, Distraction/methods* ; Recombinant Proteins/therapeutic use ; Reconstructive Surgical Procedures/methods* ; Reproducibility of Results ; Skull/pathology ; Skull/surgery* ; Stress, Mechanical ; Time Factors ; Tomography, X-Ray Computed/methods ; Transforming Growth Factor beta/therapeutic use*
Abstract
BACKGROUND:
Transport distraction osteogenesis (TDO) has been used in attempts to treat large calvarial defects but has, until now, lacked consistency and reliability. To achieve sufficient bone formation, the effect of TDO was compared to the effect of TDO combined with recombinant human bone morphogenic protein-2 (rhBMP-2).
METHODS:
Fourteen dogs were divided into 2 groups; 6 animals in the control group received TDO only, and 8 received TDO combined with rhBMP-2. A calvarial defect 33 × 35 mm in size was generated, and the drug-delivering internal distractor was applied. After a 5-day latency period, distraction with rhBMP-2 at 10 μg/day was initiated at a rate of 2 mm/day. This was followed by a consolidation period of 3 months, after which areas of osteogenesis and strength were measured and histologic examinations were conducted.
RESULTS:
The average area of osteogenesis was higher in the experimental group (P < 0.01). Regenerated bone of the experimental group showed increased strength (P < 0.05). Histological examination showed typical mature bone in the experimental group. Prominent osteoblastic rimming was observed in the bone marrow of the experimental group.
CONCLUSIONS:
TDO with an internal distraction device delivering rhBMP-2 can enhance bone regeneration of large calvarial defects in a dog model. These results suggest the potential for human clinical testing of TDO combined with rhBMP-2.