Angiogenesis during mandibular distraction osteogenesis

Recruitment of a blood supply is critical for successful bone induction and fracture healing. Despite the clinical success of distraction osteogenesis (DO), an analysis of angiogenesis during membranous bone DO has not been p erformed. The purpose of this study was to evaluate the temporal and spatia l pattern of angiogenesis during mandibular DO. The right hemimandible of a dult male rats was osteotomized, and a customized distraction device was ap plied. Following a 3-day latency period, distraction was begun at a rate of 0.25 mm twice daily for 6 days (3.0 mm total; 12% increase in mandibular l ength). Three animals each were sacrificed on days 2, 4, and 6 of distracti on (D1, D2, and D3 respectively), or after 1, 2, or 4 weeks of consolidatio n (C1, C2, and C3 respectively). Two experienced pathologists reviewed the regenerate histology, and angiogenesis was assessed by counting the number of blood vessels per intermediate-power field (IPF). Statistical analysis w as performed using analysis of variance, with p less than or equal to 0.05 considered significant. Results demonstrate that mandibular DO was associat ed with an intense vascular response during the early stages of distraction (D1). On average, 31.5 +/- 7.9 vessels were noted in each IPF examined dur ing this time point. The number of blood vessels in the distraction regener ate decreased significantly during the later distraction time points, with approximately 14.0 +/- 2.0 and 14.7 +/- 3.5 blood vessels per IPF in sectio ns obtained after days 4 and 6 of distraction (D2, D3) respectively. Howeve r, blood vessels at these time points took on a more mature histological pa ttern. During the consolidation period, the number of blood vessels noted i n the regenerate decreased with 8.0 +/- 2.6, 9.3 +/- 2.1, and 4.0 +/- 2.0 v essels per IPF in sections obtained after 1, 2, or 4 weeks of consolidation (C1, C2, C3) respectively (p < 0.05 compared with vessel counts during the earliest distraction time point). This study demonstrates for the first ti me that an intense vascular response associated with mandibular DO occurs p rimarily during the early stages of distraction. The authors hypothesize th at as distraction continues, newly formed vessels likely undergo consolidat ion, thus forming more mature vessels capable of withstanding distraction f orces. Future studies will assess the effects of therapeutic interventions designed to increase angiogenesis during DO on bony regenerate formation.