title: Callus stimulation in distraction osteogenesis.
abstract: Distraction osteogenesis has been described as in vivo tissue engineering. The ability to stimulate this process for the repair of bony defects or lengthening of congenitally shortened facial structures is likely to significantly impact the field of craniofacial surgery. The purpose of this study was to determine whether mechanical stimulation of the distracted rabbit mandible would accelerate the maturation of the bony callus when applied during the early consolidation period. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A uni-directional internal distractor device (Synthes, Paoli, Pa.) was positioned along a plane perpendicular to the line of osteotomy. After a 7-day latency period, distraction was commenced at a rate of 1.0 mm/day for 12 days in all animals. In a control group of 10 rabbits, a consolidation period of 8 weeks was observed before they were killed. In the experimental group of 10 rabbits, daily alternate compression and distraction of 1 mm (sequential compression and distraction) was performed for 3 weeks followed by a 5-week period of rigid fixation. Each animal received a dose of a fluorescent label at three different time points during the study: at the end of the distraction period, 3 weeks after the completion of the distraction phase, and 3 days before it was killed. All animals were killed 8 weeks after the completion of the distraction phase. Undecalcified histologic analysis and 3-point bending tests to failure were performed on the extracted mandibles. The results of the experimental and control groups were compared. Four animals in the control group and three animals in the experimental group were excluded from the study because of screw loosening resulting in distractor dislodgment or because of infection. On histologic analysis, cortical thickness at the center of the callus was found to be significantly greater in the experimental group compared with the control group when normalized to the contralateral hemimandible (83 percent versus 49 percent, respectively; p < 0.007). The ratio of cortical to cancellous bone in the distracted callus was uniformly found to be greater in the experimental specimens. The mineral apposition rate was calculated by using fluorescence microscopy and found to be significantly greater in the experimental group both during the period of sequential compression and distraction (3.2 microm/day versus 2.1 microm/day, p = 0.02) and after the period of sequential compression and distraction (1.4 microm/day versus 1.1 microm/day, p = 0.006). Mechanical testing revealed no significant differences in bending strength or stiffness between experimental or control groups (p = 0.54 and 0.47, respectively). This study has demonstrated that daily alternating compression and distraction of 1 mm amplitude during the early consolidation period has a stimulatory impact on callus formation with respect to osteoblastic activity, remodeling, and maturation of bone. Optimal timing and amplitude of sequential movement, long-term biomechanical differences, and molecular pathways have yet to be elucidated.
authors.affiliation: Department of Surgery, Division of Plastic, Reconstructive, and Maxillofacial Surgery, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Mehrdad M
authors.initials: MM
authors.lastname: Mofid
authors.forename: Nozomu
authors.initials: N
authors.lastname: Inoue
authors.forename: Atay
authors.initials: A
authors.lastname: Atabey
authors.forename: Guy
authors.initials: G
authors.lastname: Marti
authors.forename: Edmund Y S
authors.initials: EY
authors.lastname: Chao
authors.forename: Paul N
authors.initials: PN
authors.lastname: Manson
authors.forename: Craig A
authors.initials: CA
authors.lastname: Vander Kolk
mesh_terms: D000818:Animals; D002146:Bony Callus / Q000502:physiology*; D005260:Female; D008297:Male; D019857:Osteogenesis, Distraction / Q000379:methods*; D011817:Rabbits