Angiogenesis during mandibular distraction osteogenesis
Angiogenesis during mandibular distraction osteogenesis
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DOI：
10.1097/00000637-199905000-00002
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发表时间：
1999-05-01
影响因子：
1.5
通讯作者：
Longaker, MT
中科院分区：
文献类型：
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作者：
Rowe, NM;Mehrara, BJ;Longaker, MT
血供的恢复对于成功的骨诱导和骨折愈合至关重要。尽管牵引成骨(DO)在临床上取得了成功，但对膜性骨DO过程中血管生成的分析还没有进行。本研究的目的是评估下颌骨DO过程中血管生成的时间和空间模式。将成年雄性大鼠右侧下颌骨截骨，并应用定制的牵张器。在3天潜伏期后，以0.25 mm的速度开始牵张，每天两次，持续6天(总共3.0 mm；下颌长度增加12%)。在牵张的第2、4、6天(分别为d1、d2、d3)，或在固定后1、2、4周(分别为c1、c2、c3)各处死3只动物。两位经验丰富的病理学家回顾了再生组织学，并通过计算每个中倍视野(IPF)的血管数量来评估血管生成。使用方差分析进行统计分析，其中p小于或等于0.05被认为是显著的。结果表明，在牵张早期(D1)，下颌骨的DO与强烈的血管反应有关。在这一时间点上，平均每个IPF检查记录到31.5+/-7.9条血管。在牵张后的时间点，牵张再生的血管数量显著减少，在牵张后4天和6天(D2、D3)，每个IPF的血管数分别为14.0+/-2.0和14.7+/-3.5条。然而，这些时间点的血管呈现出更成熟的组织学模式。在固定期间，在固定后1周、2周和4周(C1、C2、C3)，再生的血管数量分别减少了8.0+/-2.6、9.3+/-2.1和4.0+/-2.0个/IPF(p<；0.05与最早牵张时间点的血管计数相比)。这项研究首次证明，与下颌DO相关的强烈血管反应主要发生在牵张的早期阶段。作者假设，随着分心的继续，新形成的血管可能会发生巩固，从而形成更成熟的能够承受分心力量的血管。未来的研究将评估旨在增加DO期间血管生成的治疗干预对骨再生形成的影响。
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 performed. The purpose of this study was to evaluate the temporal and spatial pattern of angiogenesis during mandibular DO. The right hemimandible of adult male rats was osteotomized, and a customized distraction device was applied. 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 length). Three animals each were sacrificed on days 2, 4, and 6 of distraction (D1, D2, and D3 respectively), or after 1, 2, or 4 weeks of consolidation (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 was performed using analysis of variance, with p less than or equal to 0.05 considered significant. Results demonstrate that mandibular DO was associated 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 during this time point. The number of blood vessels in the distraction regenerate decreased significantly during the later distraction time points, with approximately 14.0 +/- 2.0 and 14.7 +/- 3.5 blood vessels per IPF in sections obtained after days 4 and 6 of distraction (D2, D3) respectively. However, blood vessels at these time points took on a more mature histological pattern. During the consolidation period, the number of blood vessels noted in the regenerate decreased with 8.0 +/- 2.6, 9.3 +/- 2.1, and 4.0 +/- 2.0 vessels 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 time that an intense vascular response associated with mandibular DO occurs primarily during the early stages of distraction. The authors hypothesize that as distraction continues, newly formed vessels likely undergo consolidation, thus forming more mature vessels capable of withstanding distraction forces. Future studies will assess the effects of therapeutic interventions designed to increase angiogenesis during DO on bony regenerate formation.