较大速率牵引成骨术对山羊下牙槽神经的影响

目的 研究较大速率牵引成骨术(DO)对山羊下牙槽神经(IAN)的影响,探讨下颌骨较大速率DO的可行性.方法 9只山羊双侧下颌骨行DO,术中预置牵开间隙3.5 mm,延迟期为3 d,牵引速率为1.5 mm/d,分3次牵引,延长幅度为20 mm.3、5、7、12周行X线、大体和组织学观察.结果 下牙槽神经管周壁完整,血管神经束表面光滑,外观未见神经损伤,牵引完成后初期(3周),IAN表现为较为广泛的Waller变性,中后期(5～7周)神经有再生修复改变,神经内膜及束膜完整,12周时已趋于正常,亦无纤维化改变.结论 下颌骨DO术中预置间隙(3.5 mm),缩短延迟期(3 d),适当提高牵引速率和频率(1.5 mm/d,3次/天),IAN的退行性变是可逆的.     

硫酸钙人工骨对山羊下颌骨牵引成骨的影响

目的建立山羊双侧下颌骨牵张成骨实验动物模型,探讨硫酸钙人工骨对山羊下颌骨牵引成骨区新骨生成的作用及局部使用硫酸钙对血清总钙的影响。方法8只山羊随机分为A组（硫酸钙组）和B组（对照组）．建立牵引成骨（Distraction Osteogenesis,DO）模型。A组预牵开3mm间隙,注入硫酸钙人工骨;B组常规牵引：两组均于术后第5天开始,以0．5mm／12h的速度牵引,A组连续牵引7d,B组连续牵引10d,两组颌骨总延长距离均达到10mm。术前及术后早期检测血清碱性磷酸酶（ALP）和血清总钙浓度。牵引结束后第6周取材,对新生骨大体标本、影像学、组织学、骨密度及生物力学等指标进行观察检测。结果所有山羊下颌骨均延长了约10／mm,A组血清ALP浓度、新生骨小梁面积百分比、骨密度及三点弯曲断裂最大载荷值均比B组高（P〈0．05）,而血清总钙浓度与B组相比差别无显著性（P〉0．05）。结论动物实验表明,硫酸钙人丁骨在牵引成骨的早期对新骨的形成具有促进作用．且局部应用硫酸钙对血清总钙浓度无明显影响．具有良好的生物相容性。     

促进下颌骨牵引成骨新骨形成的研究进展

牵引成骨技术（distraction osteogenesis，DO）因其能在原位快速成骨而被称为是一种内源性组织工程技术。然而，DO的某些并发症（如骨再生不良、延迟愈合、不愈合），特别是其较长的疗程及牵引装置长时间留置于面部或口腔内所引发的各种问题（如固定螺钉松脱、伤口感染、骨折等）成为临床应用和推广该项新技术的瓶颈和主要障碍。     

内置式下颌骨牵引成骨术及其常见并发症的处理

目的 探讨内置式下颌骨牵引成骨术的常见术后并发症发生的原因及防治措施。方法 总结分析1997至2004年采用内置式下颌骨牵引成骨术治疗下颌骨畸形或缺损患者46例61侧，其中半侧颜面短小27例，下颌骨发育不足或小颌畸形双侧8例、单侧4例，电击伤或肿瘤术后缺损畸形3例，Treaeher Colins综合征2例，睡眠呼吸暂停综合征2例。结果 46例61侧发生并发症者9例，包括牵引机械装置故障3例，局部感染2例，前牙开骀2例，皮肤窦道2例。经积极处理后均达到预期治疗目的。结论 减少下颌骨牵引成骨术并发症的关键在于充分理解下颌骨牵引成骨术的机理，熟悉掌握下颌骨及邻近解剖结构，操作规范熟练，充分的术前准备和术后处理尤为重要。     

兔双侧下颌骨牵引成骨动物模型的建立

目的:使用CBX01-15型兔下颌骨专用牵引器,建立兔双侧下颌骨牵引成骨动物模型,并评价其牵引效果。方法:新西兰大白兔8只,行双侧下颌骨截骨术,安置牵引器。延迟5天后,两侧下颌骨均以0.5mm/次,2次/天的速度牵引15天,牵引结束后固定8周,新骨分别行大体、放射学和组织学检查。结果:所有动物均良好耐受牵引及固定,未发生死亡,双侧下颌体均显著延长。固定8周时,两侧新骨均接近正常骨。结论:兔双侧下颌骨牵引成骨动物模型牵引效果可靠,新骨再生良好。     

骨基质明胶影响狗下颌骨牵张成骨的实验研究

目的探讨在牵张区截骨部位加入骨基质明胶（Bone matrix gelatin，BMG），以诱导骨的再生，促进牵张区骨痂愈合，并缩短间歇期及固定期，提高成骨质量，减少并发症。方法选用6只雄性成年杂种狗，随机选取一侧作为实验组（牵张区截骨部位加入BMG），另一侧作为对照组。分别在下颌骨体部安放牵张器，共牵张7d，通过不同时间点的X线观察、组织学观察和灰度分析来评价骨牵张的程度。结果计算机辅助灰度间接计量统计学分析结果：第1周时，对照组和实验组的骨密度间接计量值，两者比较差异无统计学意义。第3周、5周、8周时，对照组和实验组的骨密度间接计量值，两者比较，差异有统计意义。结论在牵张区截骨部位加入BMG，能够诱导骨的再生，可促进牵张区骨痂愈合，缩短牵张成骨整个过程．提高成骨质量，减少并发症。     

下颌骨牵张成骨的有限元模拟

目的：建立下颌骨牵张成骨的有限元模型,以了解下颌骨牵张成骨形变发生的生物力学基础和形变规律。方法将下颌骨CT数据导入Mimics 10.1,按临床设计的截骨线位置进行模拟截骨,然后将数据输入Magics 9.9中进行模型优化。输入Ansys 12.0建模,并进行下颌骨牵张成骨的模拟。结果牵张成骨的位移变化、应力及软组织改变均可直观有效地模拟。结论有限元分析可以总结手术效果,分析应力分布及软组织阻力方向,提出治疗过程的改进意见。     

山羊颈椎间盘纤维环成纤维细胞成骨潜能的体外观察

目的 诱导培养椎间盘纤维环成纤维细胞，探讨其成骨潜能，比较重组人骨形成蛋白2（recombinant human bone morphogenetic protein2，rhBMP-2）和肿瘤坏死因子α（tumor necrosis factor α，TNF—α）对其成骨的不同影响。方法利用体外细胞培养技术，建立实验山羊颈椎间盘纤维环成纤维细胞培养体系，根据培养液的不同，分为空白对照组、TNF-α组（加入50U／ml TNF-α）、rhBMP-2组（加入0．1μg／ml rhBMP-2）和TNF—α＋rhBMP-2组（加入50U／ml TNF-α＋0．1μg／ml rhBMP-2），培养3周观察纤维环成纤维细胞在条件培养液诱导下的成骨表型变化、碱性磷酸酶（alkaline phosphatase，ALP）和骨钙素（osteocalcin，OC）等成骨指标变化。结果 各实验组培养液对细胞增殖无明显影响。rhBMP-2组和TNF-α＋rhBMP-2组细胞趋化性生长明显，矿化结节出现，茜素红染色呈深红色钙阳性反应。各实验组ALP活力与空白对照组比较差异均有统计学意义（P〈0．05）。rhBMP-2组与TNF—α＋rhBMP-2组成纤维细胞的OC分泌量与空白对照组比较差异均有统计学意义（P〈0．05），TNF—α组与空白对照组比较差异无统计学意义（P〉0．05）。结论 体外培养的椎问盘纤维环成纤维细胞有成骨潜能，rhBMP-2对纤维环成纤维细胞有明确的诱导成骨作用。     

牵张成骨术在延长下颌骨中新骨生成方式的研究

目的　探讨山羊下颌骨牵张成骨过程中新骨生成方式及其影响因素。方法　用口外牵张器 ,按1mm/天的牵张速率将 12只成年山羊的双侧下颌骨延长 10 m m,牵张结束后固定至第 2、4和 8周分别处死 4只动物 ,拍摄下颌骨 X线片后取牵张区新生骨痂作组织学观察。结果　牵张间隙内新骨组织沿牵张方向向心性生长 ,成骨方式主要是膜内成骨 ,在牵张器松动的标本早期仍可观察到散在的软骨岛。结论　牵张延长下颌骨过程中新骨生成方式主要为膜内成骨 ,软骨化骨只是在牵张器固定不良时发生。     

Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

Background

Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction.

Methods

The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed.

Results

The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection.

Conclusions

DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest that percutaneous DBM administration at the end of the distraction period or in the early consolidation period may stimulate regenerate bone formation and consolidation in a clinical situation with delayed bone healing during DO.     

Midface Membranous Bone Lengthening: A One-Year Histological and Morphological Follow-Up of Distraction Osteogenesis

Midface bone lengthening was performed on three young, adult sheep using distraction osteogenesis following osteotomy of the maxilla and mounting of an extraoral fixation device. The midface was gradually distracted, 2 mm/day, for 21 days, up to approximately 40 mm. A marked midface advancement was noted. Following a further 6 weeks of retention, the device was removed and the animals were followed for 1 year. Biopsies specimens were taken from the distracted area at the end of the distraction period, after the additional 6 weeks of retention, and finally 1 year later. A nondistracted area of the maxillary bone served as control. The specimens were analyzed histologically, histochemically, and by scanning electron microscopy for the ultrastructural pattern, mineralization, mineral content, and approximate Ca²⁺ concentration. Clinically and radiographically, all sheep fully bridged the experimental gap. Histologically, at the completion of distraction, collagen bundles and slender bone trabeculae oriented in the direction of the distraction could be seen. At the end of the retention period, the trabeculae thickened noticeably and were partially replaced by mature lamellar bone. At the end of 1 year and after completion of the process of remodeling, the pattern of the distracted area resembled the control area. The mineralization, as reflected by quantitative calcium analysis, compared with the nondistracted area, demonstrated a low rate of mineralization after 3 weeks of lengthening, increased 6 weeks later, and after 1 year became nearly the same as in the nondistracted area. In conclusion, distraction osteogenesis provides satisfactory quantitative and structural new bone. Received: 23 September 1996 / Accepted: 17 June 1997     

牵拉对兔耳软骨愈合和再生影响的实验研究

目的建立可靠的兔耳软骨牵引模型,对牵引后软骨的生长方式、愈合方式进行研究。方法 20只新西兰大白兔随机分组,每只兔随机选取一侧兔耳制作模型,实验组10只,对照组10只。实验组横向截断兔耳软骨,安装软骨牵引器,预固定2周,持续牵引2周,再固定1周;对照组术后不作牵引。于手术后即刻、预固定后、牵引后及再固定后分别取材,行HE、Masson染色,观察软骨组织生长愈合情况。对照组术后不作牵引。结果依靠外加牵引器进行持续牵引可促进兔耳软骨横向截断后产生新生的软骨细胞并修复组织缺损,基本恢复解剖形态。结论软骨截断后,通过外固定组织牵引技术能够促进软骨细胞再生和组织愈合,有望为软骨移植修复缺损提供更多的组织量。     

Expression and Role of Interleukin-6 in Distraction Osteogenesis

Distraction osteogenesis is a special form of bone healing in which well-controlled distraction stresses and consequent tensile strains within callus tissue induce very efficient new bone formation. Proinflammatory cytokines are involved during the early phase of fracture healing and callus remodeling. Temporal expression patterns of proinflammatory cytokines were assessed in Sprague-Dawley rat tibial models of distraction osteogenesis and acute lengthening, and only interleukin-6 (IL-6) was found to be specifically induced during the distraction phase. IL-6 immunoreactivity was detected not only in hemopoietic cells and osteoblasts but also in the spindle-shaped cells of the fibrous interzone, where most of the tensile strains are concentrated. In vitro study revealed that IL-6 did not affect the proliferation of C3H10T1/2 cells, mouse bone marrow stromal cells (MSCs), or MC3T3-E1 cells; but its blocking antibody reduced the proliferation of C3H10T1/2 cells and MSCs. The mRNA expression of COL1A1 and osteopontin were not changed by IL-6 or its blocking antibody, but the alkaline phosphatase activities of MC3T3-E1 cells were increased by IL-6 and decreased by its blocking antibody. These findings indicate that IL-6 is a proinflammatory cytokine that responds to tensile strain during distraction osteogenesis. IL-6 negatively affects the proliferation of primitive mesenchymal cells, whereas the differentiation of more mature osteoblastic lineage cells is enhanced by IL-6 in vitro. IL-6 appears to be one of the cytokines involved in the complex network of signal cascades evoked during distraction osteogenesis and may differentially affect immature and mature osteoblastic lineage cells.     

骨缝牵引成骨动物模型的建立及应用

目的建立兔颅骨矢状缝牵引成骨的动物实验模型,评价该模型的可行性,并探讨局部应用rhBMP-2对牵引成骨的作用。方法以微型牵引种植钉(Miniscrew implants,MSI)作支抗,镍钛弹簧为牵引力源,建立MSI兔颅骨矢状缝弹力牵引成骨模型。应用该牵引系统对11周龄的新西兰白兔作矢状缝牵引成骨。将动物随机分为实验组(牵引+rh BMP-2,n=7),对照组(单纯牵引,n=7)。牵引29天,于0、5、11、17、23及29 d,应用X线及Micro-CT评价骨缝牵开情况;第7、27天注射四环素,第17天注射钙黄绿素,作为术后荧光组织切片观察标记。观察动物对该牵引成骨系统的耐受性,比较各组骨缝牵开的距离,并观察矢状缝组织形态学变化,验证兔颅骨矢状缝牵引成骨模型的可行性。结果MSI弹力牵引系统成功率为86%,牵引成骨实验可顺利完成。对照组矢状缝牵开的距离大于实验组(D29),两组矢状缝牵开的距离随着牵引持续时间的增加而递增,但骨缝牵开呈现先快后慢的趋势。骨组织形态学显示,两组骨缝间均有新生骨组织形成,说明该牵引成骨模型既能有效牵开骨缝,也能诱导骨缝间成骨。而实验组骨缝间新生骨组织形成速度大于对照组。结论本实验采用自行研制的微型种植钉MSI弹力牵引系统,成功建立了兔矢状缝弹力牵引成骨模型。骨缝牵引过程中,局部应用rhBMP-2可促进骨缝成骨,但导致了骨缝融合。