双维控制牙槽骨牵张器的成骨效应

背景：牵张成骨增高牙槽嵴在基础研究及临床已有很多成功报道,双维控制垂直牙槽骨牵张器可有效防止单向直线牵张器行牙槽骨牵张发生轴向移位。 目的：研制双维控制的牙槽骨牵张器,并通过动物实验观察其成骨效应。 方法：选择杂种犬4只,拔除一侧下颌前磨牙形成萎缩牙槽骨模型。1个月后行骨切开放置双维牵张器,7 d后垂直牵张 (1 mm/d,共5 d)。完成垂直牵张后,利用双维牵张器颊向控制功能将移动骨块颊向牵出(大约2.4 mm),固定2个月后行大体观察及组织学检查。 结果与结论：4只犬中2只黏膜伤口愈合良好,2只黏膜出现裂开,行二次缝合后愈合,牵张器固位良好,未出现松动、脱落。牵张骨块向垂直向及颊向的位移量满足实验目的要求,牙槽骨垂直向高度平均增加(5.0±0.2) mm,颊向宽度平均增加(2.4±0.3) mm。大体观察及组织学检查均证实牵张成骨的骨块新骨形成良好。说明双维控制垂直牙槽骨牵张器能较好的控制移动骨块垂直或颊向的移动方向,并且新骨形成良好。     

牵张延长下颌骨对二腹肌纤维型构成影响的研究

目的 :研究牵张延长下颌骨前后二腹肌的组织化学特征。方法 :应用肌球蛋白ATP酶 (pH9.4)染色法 ,观测了牵张前后 8只狗的二腹肌肌纤维类型 ,并用VIDAS图像分析仪测量其横截面积。结果 :ATP酶染色 ,二腹肌肌纤维分为Ⅰ型和Ⅱ型 ,Ⅰ型纤维数量较Ⅱ型纤维少。牵张延长下颌骨后 ,Ⅰ型纤维数量显著性增多 ,Ⅱ型纤维数量显著性减少。牵张成骨后 ,Ⅰ型纤维、、Ⅱ型纤维的横截面积与术前比较没有显著性差异。结论 :牵张延长下颌骨后 ,与牵张方向平行的二腹肌肌纤维型分布发生了与功能变化相适应的改变     

Strategies of enhancing bone regenerate formation in distraction osteogenesis

Distraction osteogenesis (DO) is a commonly used technique in multiple orthopedic sub-specialties, including trauma, oncology and pediatrics. This technique aims to produce new bone formation in the distraction gap in a controlled manner. The issue with this technique has been the high risk of complications, one of which is poor regenerate formation during the distraction process. Although several factors (including patient and operative factors) and techniques (including surgical, mechanical and pharmacological) have been described to ensure successful regenerate formation during the process of DO, these factors are sometimes difficult to control clinically. Our aim from this review is to highlight the different factors that affect DO, modalities to assess the regenerate and review treatment options for poor regenerate in the distraction gap. In addition, we propose a management protocol derived from the available literature that can be used to facilitate the management of inadequate regenerate formation.     

骨形态形成蛋白在下颌骨快速牵张成骨中的应用*

背景：牵张成骨已经成为治疗不同类型颅面畸形和骨缺损的有效的方法,但是牵张成骨的主要缺点是牵张期和稳定期比较长,可能导致牵张过程中严重的并发症。 目的：总结骨形态形成蛋白在快速牵张成骨过程中作用的研究现状。 方法：电子检索计算机Pubmed数据库(1989/2011)收录的骨形态形成蛋白和牵张成骨相关综述和论文报告。 结果与结论：共纳入骨形态形成蛋白在快速牵张成骨中的作用相关文献32篇。骨形态形成蛋白具有很强的成骨活性,能促进骨再生和骨改建。目前的研究显示应用骨形态形成蛋白能加快牵张成骨过程中新骨形成和缩短治疗的疗程。但是骨形态形成蛋白应用于临床还需要进一步的研究。     

Biomechanical response of a mandible in a patient affected with hemifacial microsomia before and after distraction osteogenesis

Distraction osteogenesis (DO) has gained wide acceptance in the craneofacial surgery due to the huge possibilities it offers. However this orthopaedic field is under continuous development as it still presents uncertainties. In this context, numerical modelling/analysis may help us to design patient specific treatments once they have been experimentally verified. This paper presents a finite element analysis of the biomechanical behavior of a patient's mandible with hemifacial microsomia (HFM) before and after distraction. In order to check the effectiveness of the clinical protocol, the predicted biomechanical response will also be compared with that of a symmetrical healthy mandible. Strain and displacement fields, masticatory forces as well as reaction forces at the condyles are evaluated in each mandible analyzed. The results show that the present model is a useful tool to understand the normal function of the mandible and to predict changes due to alterations in the mandible geometry, such as those occurring in hemifacial microsomia.     

下颌骨牵引成骨过程中基因干预对牵引区转化生长因子β1表达的影响?****

 背景：局部基因治疗能促进牵引区新骨的生成,但关于基因治疗后对局部生长因子表达的影响目前尚不清楚。 目的：观察电穿孔介导的基因治疗对兔下颌骨牵引成骨过程中转化生长因子β1表达的影响。 方法：新西兰大白兔双侧下颌骨截骨后3 d开始下颌骨牵引,0.8 mm/d,连续牵引7 d后,随机分为5组,分别在牵引区注射2 μg(0.1 g/L)重组质粒pIRES-hVEGF165-hBMP2、pIRES-hBMP2、pIRES-hVEGF165、空质粒pIRES及相同剂量的生理盐水。之后施加电穿孔刺激。 结果与结论：免疫组织化学染色发现转化生长因子β1主要在细胞胞浆中表达,给药7 d时骨端骨细胞、编织骨痂骨细胞、骨痂表面成骨细胞呈转化生长因子β1染色阳性;14 d时新生成的编织骨痂骨细胞、骨痂表面成骨细胞、肉芽组织中的间质细胞、单核巨细胞、多核巨细胞转化生长因子β1染色阳性;28 d时转化生长因子β1阳性细胞明显减少。其中注射重组质粒pIRES-hVEGF165-hBMP2、pIRES-hBMP2、pIRES-hVEGF165后转化生长因子β1的表达明显多于注射空质粒pIRES及生理盐水(P < 0.05或P < 0.01)。说明基因治疗能促进转化生长因子β1的表达,促进牵引区细胞基质的形成和新骨生成。       

大鼠腭中缝牵张成骨中骨形态发生蛋白7的作用

背景：已有实验证实,骨形态发生蛋白7可诱导骨组织和软骨组织的形成,在牵张成骨的过程中促进骨组织形成。 目的：测定骨形态发生蛋白7在腭中缝牵张成骨中的作用及机械扩张力作用下的变化。 方法：采用自制双眼扩弓簧对大鼠施加扩张力,建立上颌骨扩张大鼠模型。分别于建模后第1,3,5,7,9,12,14天随机选取大鼠取腭中缝组织,实时定量PCR法测定目的基因的变化规律。 结果与结论：建模后第3,9,12,14天大鼠腭中缝组织骨形态发生蛋白7 mRNA的表达逐渐升高(P < 0.05)。结果证实,大鼠腭中缝牵张成骨时,骨形态发生蛋白7 mRNA在机械力刺激下表达明显上调。     

脂联素对兔下颌快速牵张成骨的影响☆

背景：脂联素可参与骨代谢及成血管过程,但目前关于脂联素对牵张成骨有无促进作用尚不清楚。 目的：通过建立兔下颌快速牵张动物模型,探讨局部应用脂联素对骨牵张新骨再生的影响。 方法：16只新西兰大白兔随机摸球法均分为对照组及实验组,建立兔下颌单侧快速牵张模型,牵张速率为2 mm/d。在牵张开始的1,3,5 d,对照组及实验组分别于牵张间隙注入200 μL磷酸盐缓冲液或含有2 μg重组人脂联素的磷酸盐缓冲液。 结果与结论：两组动物牵张间隙内均可观察到新骨生成,组织学及显微CT检查显示实验组的新骨生成与钙化明显高于对照组。实验结果显示局部应用脂联素可有效促进兔下颌快速骨牵张的新骨再生。 关键词：脂联素;牵张成骨;动物模型;新骨再生;下颌骨 doi:10.3969/j.issn.1673-8225.2012.11.002      

胫骨牵引成骨过程中骨形态形成蛋白4及其受体的表达

背景：骨形态形成蛋白4及其受体在骨再生和修复过程中起着重要的作用,但具体机制尚不清楚。 目的：建立小鼠胫骨牵引成骨模型,分析骨形态形成蛋白4及其受体在牵引成骨过程中的表达,探讨机械牵张力转化为生物信号从而调节骨再生过程的机制。 方法：健康雄性8周龄CD-1小鼠36只,按照手术时间随机分成术后第5,9,13,17,24和31天组,每组6只。所有小鼠均接受左胫骨中上段低能截骨,安置体外延长固定架,截骨后5 d为静止期;截骨后第6天起开始每天进行胫骨延长,速率为0.2 mm,2次/d,共12 d,为牵引期;自第18天停止牵引,为固塑期。于术后第5,9,13,17,24和31天分别处死动物,采集胫骨标本,作组织学检查、RT-PCR和原位杂交实验分析骨形态形成蛋白4及其受体激活素样激酶3以及骨钙素的表达。 结果与结论：组织学检查显示静止期修复过程基本与骨折愈合过程相似。小鼠骨折断端在持续牵引下有明显的骨痂形成,骨形态形成蛋白4及其受体激活素样激酶3以及骨钙素的mRNA的表达明显增强。结果表明,牵引成骨是一种持续的骨再生过程,机械张力可通过刺激骨形态形成蛋白4及其受体以及骨钙素的持续高表达维持骨痂的不断形成和再塑,以充填连续延长的骨折间隙。     

失神经支配在胫骨牵张成骨延长过程中的骨再生及Runx2表达

背景：研究发现,去除坐骨神经会导致骨折愈合过程中新生编织骨机械硬度不足,而目前对有关失神经因素在牵张成骨过程中作用的相关报道较少。 目的：构建新西兰大白兔胫骨牵张成骨模型,观察失坐骨神经对牵张成骨过程中新骨形成的影响及Runx2表达的变化。 方法：成年新西兰雄性白兔24只建立兔胫骨牵张成骨延长模型,并随机分为切除坐骨神经组和保留左坐骨神经组。完成牵张6周后,用X射线、骨密度及三维CT重建技术检测已延长的胫骨,组织学分析新骨形成情况。 结果与结论：影像学、组织学检查显示所有实验动物的牵张裂隙中均可发现有新骨生成,Runx2均有不同程度的表达。但与保留左坐骨神经组相比,切除坐骨神经组牵张裂隙中新生骨量较少、矿化程度低,并且Runx2表达量较低。提示失神经支配抑制牵张成骨中新骨的生成及Runx2的表达,神经支配可能在牵张成骨的新骨生成过程中起重要作用。中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Early injection of OP-1 during distraction osteogenesis accelerates new bone formation in rabbits

Distraction osteogenesis (DO) is a surgical technique for generating new bone by applying controlled distraction of two bony segments post osteotomy. A limitation of the technique is the long time required for the new bone to consolidate. We investigated the effect of injecting osteogenic protein 1 (OP-1) at the beginning of distraction in a rabbit model of DO. Regenerate bone was evaluated using radiology, densitometry, micro-computed tomography (microCT) and histomorphometry. Immunohistochemsitry was used to evaluate changes in expression of various ligands, growth factors and receptors following OP-1 treatment. Compared to the control, a two-fold increase in bone volume was apparent for treated groups at 3 weeks post injection. An upregulation of almost all of the 41 genes examined was observed. Results suggested that applying OP-1 early during distraction can accelerate bone formation by the activation of numerous pathways. This study provides further insights on strategies to improve bone regeneration rate in DO.     

Early injection of OP-1 during distraction osteogenesis accelerates new bone formation in rabbits

Distraction osteogenesis (DO) is a surgical technique for generating new bone by applying controlled distraction of two bony segments post osteotomy. A limitation of the technique is the long time required for the new bone to consolidate. We investigated the effect of injecting osteogenic protein 1 (OP-1) at the beginning of distraction in a rabbit model of DO. Regenerate bone was evaluated using radiology, densitometry, micro-computed tomography (microCT) and histomorphometry. Immunohistochemsitry was used to evaluate changes in expression of various ligands, growth factors and receptors following OP-1 treatment. Compared to the control, a two-fold increase in bone volume was apparent for treated groups at 3 weeks post injection. An upregulation of almost all of the 41 genes examined was observed. Results suggested that applying OP-1 early during distraction can accelerate bone formation by the activation of numerous pathways. This study provides further insights on strategies to improve bone regeneration rate in DO.     

骨髓间充质干细胞诱导成骨的研究进展

骨髓间充质干细胞因其具有自我复制和多向分化潜能而成为目前骨组织工程领域研究的重点之一。对这方面近几年的研究成果从诱导因子的作用及调控机制、物理条件、新的研究方法等方面做了简要论述。     

富血小板纤维蛋白对兔下颌骨牵引成骨区骨形态发生蛋白-4表达的影响

目的:探讨富血小板纤维蛋白(PRF)对牵引成骨区骨形态发生蛋白-4(BMP-4)表达的影响。方法:25只大耳白兔随机分2组,分别行双侧下颌骨皮质骨切开术,一侧下颌骨牵引间隙放置PRF膜作为实验组,对侧作为对照组,分别于稳定期第3、7、14、21、28天处死一组动物,切取牵引间隙处骨痂行H-E染色和BMP-4免疫组织化学显色,细胞图像分析仪测量牵引间隙处骨痂BMP-4表达情况。结果:下颌牵引延长后牵引间隙均有新骨形成,免疫组织化学显色显示BMP-4主要定位于成骨细胞的细胞质中。实验组在稳定期3、7、14、21 d BMP-4表达的阳性细胞率和阳性面积百分比均显著高于对照组,稳定期28 d BMP-4表达的阳性细胞率和阳性面积百分比与对照组比较差异均无统计学意义。结论:PRF能促进兔下颌骨牵引成骨区新骨的生成,BMP-4可能在牵引成骨过程中调控组织细胞应力信号传递,发挥成骨作用。     

The effect of distraction rate on bone histological and histomorphometrical properties in an ovine mandible model

Lengthening the mandible by distraction osteogenesis (DO) is nowadays a well-recognized technique in maxillofacial surgery. This study compared two different distraction rates and evaluated histological and histomorphometrical properties of the distracted bone in an experimental ovine mandible model with the goal of elaborating a universally accepted distraction protocol. Study Design: Tissue blocks of regenerated bone were harvested from twelve young adult sheep. DO was performed on the mandibular midline after five days of latency period. The sheep were divided into two groups. The first group underwent activation of 0.8 mm÷day during 12 days resulting in 9.6 mm of new bone while the second group followed a geometric rate pattern of 0.2 mm - three days, 0.4 mm - three days, 0.8 mm - three days and 1.6 mm - three days resulting in 9 mm of new bone. The regenerated bone was histologically and histomorphometrically analyzed after 30, 45 and 60 days of consolidation. The relative osteoid volume (OV÷TTV) was significantly increased in the geometric rate distraction group (p=0.015) comparing with linear distraction group while the relative bone volume (BV÷TTV) was significantly increased in the linear distraction group (p=0.019) compared to the geometric distraction group.     

血管内皮生长因子缓释系统复合成骨诱导的骨髓间质干细胞修复骨缺损

背景：从目前文献报道来看,生长因子缓释系统在骨科方面的应用研究主要集中在软骨修复方面,关于复合组织工程骨修复骨缺损的研究报道较少。 目的：构建复合组织工程骨,观察其修复骨缺损的效果。 方法：①通过血管内皮生长因子、肝素和纤维蛋白胶的不同组合构建复合支架缓释系统,经检测选取最优组种植成骨诱导的骨髓间质干细胞构建复合组织工程骨。②36只SD大鼠制备股骨干骨缺损模型后随机分为3组,分别植入上述复合组织工程骨和复合支架缓释系统,空白对照组不植入任何材料,3组均予内固定。③ELISA方法检测样本释放的血管内皮生长因子浓度以评价复合支架缓释系统的缓释性能;于植入后1,4,12,24周行X射线检查及骨组织碱性磷酸酶染色评价各组动物骨缺损修复水平。 结果与结论：经血管内皮生长因子/肝素/纤维蛋白修饰的纳米晶胶原基骨复合支架缓释系统在体外环境缓释30 d后依然高浓度释放血管内皮生长因子,且缓释曲线平直;动物实验中植入的复合组织工程骨在24周内完全降解,骨缺损修复完成,骨缺损部位碱性磷酸酶活性明显高于复合支架缓释系统组、空白对照组。结果显示该复合支架缓释系统具有优异的缓释性能,在该缓释系统上种植成骨诱导的骨髓间充质干细胞后,能够提高骨缺损修复的速度和质量。     

Survival with the acquired immunodeficiency syndrome. Experience with 5833 cases in New York City

In a cohort of 5833 subjects in whom the acquired immunodeficiency syndrome (AIDS) was diagnosed in New York City before 1986, the cumulative probability of survival (mean +/- SE) was 48.8 +/- 0.7 percent at one year and 15.2 +/- 1.8 percent at five years. The group with the most favorable survival rate--white homosexual men 30 to 34 years old who presented with Kaposi's sarcoma only--had a one-year cumulative probability of survival of 80.5 percent; that group was used as the reference group in assessing the effect of five variables: sex, race or ethnic background, age, probable route of acquiring AIDS (risk group), and manifestations of AIDS at diagnosis. The range in the mortality rate was greater than threefold, depending on these variables. Black women who acquired the disease through intravenous drug abuse, for example, had a particularly poor prognosis. The manifestations of disease at diagnosis had the most influence on survival, accounting on average for 56.3 percent of the excess risk. This variable was followed in importance by age (12.2 percent), race or ethnicity (10.6 percent), risk group (8.4 percent), and sex (8.0 percent), with 4.5 percent of the risk attributable to interactions between variables. When we compared subcohorts based on the year of diagnosis (1981 through 1985), we found a significant improvement in the one-year cumulative probability of survival among subjects with Pneumocystis carinii pneumonia, but not among subjects without P. carinii pneumonia.     

The effect of transforming growth factor beta1 (TGF-beta1) on the regenerate bone in distraction osteogenesis

Distraction osteogenesis is a well established clinical treatment for limb length discrepancy and skeletal deformities. Transforming growth factor beta 1 (TGF-beta1) is a multifunctional peptide which controls proliferation and expression of cells specific to bone like chondrocytes, osteoblasts, osteoclasts including mesenchymal precursor cells. To decrease the external fixation time with increasing the strength of regenerate (newly formed bone after distraction) we tested the effect of locally applied transforming growth factor beta 1 on distraction osteogenesis. A total of 28 mature female white New zealand rabbits weighing 3,5 kg-4,5 kg were studied. 10 animals were belonging to biomechanical testing group (5 for the study and 5 for the control subgroups), and the others were to histology group. In biomechanical group after tibial osteotomy TGF-beta1 was applied subperiosteally for 5 days just proximal to osteotomy site. Control group received only the solvent. Seven days after tibial osteotomy distraction was started at a rate of 0.25 mm/12 hours for 3 weeks with a unilateral fixator. Rabbits were sacrificed at the end of a consolidation period 8 week after tibial osteotomy. We assessed density of the elongation zone of rabbit tibial bones with the computed tomography. Then biomechanical parametres were assessed using the torsional testing using the material testing machine. In histology group rabbits were classified as control and study (rabbits that were given TGF-beta1). Rabbits were sacrificed at the end of first week, second week and fourth week also at the end of consolidation period 8 week after tibial osteotomy. Immunohistochemical and histologic parameters were examined. Biomechanical testing was applied as torsional testing. These values are used in determination of maximal loading, stiffness and energy absorbed during testing (brittleness). The histomorphometric examination looked for the differences between the study and control groups in terms of bone formation pattern, bone quality and quantity. The immunohistochemical studies investigated the mechanism of TGF-beta1, and its presence in different cell types. The results of this study suggest that locally applied TGF-beta1 improves the mineral density of distraction gap and load to failure(energy absorbed during testing). Though there is no significant histomorphometric difference between the study and control groups, there is an increased bone mineral density and an according maximum energy absorbance in the study group. This effect can be explained by the following mechanism: TGF-beta1 exerts its effect on two different receptor types (Type 1 and 2). Type 1 receptors are localized to bone matrix and type 2 receptors are localized to the intracellular space. The specific stains utilized in the current experiment are specific to type 2 receptors. They have been shown to be down-regulated by exogenous TGF-beta1 injections. Most probably, type 1 receptors are up-regulated by this exogenous administration, but unfortunately, there is currently no specific stain on tha market to display type 1 receptors and to prove this explanation.