不同牵张速率对下颌骨延长后新骨生成的影响

目的 :研究不同牵张速率延长下颌骨时对新骨生成的影响。方法 :将 12只山羊随机分为三组 ,行双侧下颌体骨皮质切开术后以三种不同牵张速率 (0 .5mm/d ,1mm/d ,2mm/d)向前延长下颌 10mm。牵张完成后第 2、4周各处死 2只山羊 ,取双侧牵张间隙内新骨组织作X光片、组织学、扫描电镜和能谱仪分析。结果 :以 0 .5mm/d和1mm/d牵张下颌骨后形成的新骨质量要好于 2mm/d。结论 :在牵张延长下颌骨时 ,1mm/d可能是最适宜的速率     

不同牵张速率对下颌骨延长后新骨生成的影响

目的：研究不同牵张速率延长下颌骨时对新骨生成的影响。方法：将12只山羊随机分为三组,行双侧下颌体骨皮质切开术后以三种不同牵张速率（0.5mm/d,1mm/d,2mm/d）向前延长下颌10mm。牵张完成后第2、4周各处死2只山羊,取双侧牵张间隙内新骨组织作X光片、组织学、扫描电镜和能谱仪分析。结果：以0．5mm/d和1mm/d牵张下颌骨后形成的新骨质量要好于2mm/d。结论：在牵张延长下颌骨时,1mm/d可能是最适宜的速率。     

兔下颌骨放疗后牵张成骨动物模型的建立

目的探讨建立兔下颌骨放疗后牵张成骨动物模型的可行性。方法24只成年新西兰大白兔随机分为放疗组和未放疗组,每组12只。放疗组采用60Co放疗机照射兔下颌骨,5.4Gy/次,隔日1次,共5次。3个月后在2组兔下颌骨的双侧截骨处安装牵张器,经5d延迟期后开始牵张,速率为1mm/d,0.5mm/次,每日2次,连续7d,共延长下颌骨7mm。固定期的第0、4、6周摄下颌骨侧位X线片。固定期的第4、6周分别取出下颌骨行组织学观察。结果兔对放疗和牵张成骨术耐受良好,未见放疗引起的不良反应。X线片有新骨形成,未见死骨;组织学观察见放疗组较未放疗组有更多软骨形成。结论兔是一种用于建立放射损伤区牵张成骨模型的良好动物。     

文摘

45.延迟期对兔下颌骨牵张成骨术的影响眼英演/AidaT…∥IntJOralMaxillofacSurg.-2003熏32穴1雪.-54-62近年来牵张成骨术(distractionosteogenesis熏DO)已广泛用于颅面骨的延长,下颌骨牵张成骨术的延迟期为0～14d。本研究通过观察兔下颌骨牵张成骨术初期不同延迟期的组织学改变,探讨下颌骨牵张成骨术的最佳延迟期。材料和方法16只日本成年白兔,重3.0～3.5kg,全麻下在下颌第一前磨牙前行双侧下颌骨皮质下截骨术,放置口外固定牵张器,按延迟期0d、2d、5d、和10d将动物分成4组,牵引速度0.25mm/12h,牵引10d处死所有动物,测量牵张间隙长度。一…     

不同牵张速率对山羊下颌骨牵张成骨中新骨形成的影响

目的:探讨山羊下颌骨牵张成骨中不同牵张速率对术后新骨形成的影响。方法:12只山羊随机分为3组,每组各4只,在对动物右下颌骨行骨皮质切开术后进行牵张,第1组动物以0.8mm/d的牵张速率进行牵张,第2组动物以1.6mm/d的牵张速率进行牵张,第3组动物以2.0mm/d的牵张速率进行牵张,随机选取实验组4只动物未手术侧正常下颌骨作为对照组。将各组新骨组织和对照组下颌骨组织分别进行骨密度检测和三点弯曲测试,对采用不同速率进行骨牵张后动物下颌骨新骨的生物力学强度和骨密度进行了对比观察。结果:0.8mm/d牵张组新骨骨密度值显著高于其余各牵张组,0.8mm/d牵张组新生骨三点弯曲实验指标均大于另2牵张组。结论:采用0.8mm/d的牵张速率进行牵张能最快促进新骨形成,提高成骨质量。     

Runx2基因转染对兔下颌骨牵张成骨的影响

目的 :探讨在兔下颌骨牵张成骨过程中,Runx2基因参与牵张过程对新骨再生的影响。方法 :选用32只新西兰白兔成功建立单侧下颌骨牵张成骨模型,随机分为实验组和对照组。牵张结束时,实验组牵张间隙内注入转染重组腺病毒(Ad5-Runx2),对照组牵张间隙内注入等体积无菌生理盐水。于牵张结束后4周末处死全部实验动物。利用组织学、影像学、双能X线(DXA)和生物力学分析等方法,对获取的下颌骨牵张标本进行检测分析。结果:三维CT重建、组织学及DXA结果证实,实验组牵张间隙内新骨生成、新骨密度和矿化含量均明显高于对照组;三点弯曲试验分析显示实验组牵张间隙最大载荷明显高于对照组。结论:Runx 2-in vivo基因治疗能够有效促进下颌牵张成骨过程中的新骨再生。     

BMP-2及Smad1在兔下颌骨垂直牵张中的表达和意义

目的：观察BMP-2及其信号传导分子Smad1在兔下颌骨垂直牵张后新骨组织中的分布和表达,探讨其在新骨形成中的作用。方法：36只兔子随机分成6组,用自制的种植型牵张器对兔下颌骨垂直牵张,以1mm/天的速度牵张4天,分别于牵后第1天、1周、2周、4周、6周取材,6只作为正常对照组。用ABC免疫组织化学法,检测兔下颌骨垂直牵张过程中不同时期BMP-2及Smad1的表达与分布。结果：免疫组化观察,牵张结束后BMP-2及Smad1阳性信号主要在间充质细胞和新生骨小梁边缘的成骨细胞表达,表达高峰在牵张后1周,以后逐渐下降,牵张后4周在骨细胞微弱表达,6周时无表达。正常对照组无表达。结论：BMP-2及Smad1/5参与兔下颌骨垂直牵张过程,并在牵张成骨的早期起作用;Smad1/5可能介导了BMP-2在牵张成骨中的信号传导。     

下颌骨缺损牵张成骨动物模型的建立

目的建立兔下颌骨缺损牵张成骨动物模型,为进一步研究牵张成骨奠定实验基础。方法25只健康成年兔随机分成6组,实验组5组,每组4只,对照组1组共5只。25只兔均行一侧下颌骨切开截骨术,实验组安置自行设计的下颌骨牵张器,经6 d间歇期后,以每天2次,每次0.4 mm的速度牵张8 d进入固定期,于牵张中期(牵张第4天)、牵张末期(牵张第8天),固定期第2、4、6周分别处死4只动物;对照组术后仅保持缺隙而不牵张,与实验组对应的每个时间点处死1只动物,取下颌骨观察骨愈合情况。结果牵张器牵张效率好,固位稳定,实验组动物的下颌骨被成功牵张,牵张区可见新骨形成。实验对照组表现为不同程度的骨不连及骨缺损。结论本研究建立的兔下颌骨缺损牵张成骨模型是较理想的动物模型。     

重组人骨形成蛋白-2促进兔下颌牵张成骨的研究

目的　研究局部应用基因重组人骨形成蛋白-2(rhBMP-2)对兔下颌牵张成骨的影响。方法　在12只成年大耳白兔的双侧下颌骨前部行骨切开术,将rhBMP-2与胶原复合植入一侧下颌骨切开处,另一侧单纯植入胶原作对照。用自行研制牵张器延长双侧下颌骨6 mm,在牵张结束后第4周处死动物,取双侧牵张区新生骨痂行组织学、扫描电镜及Ca/P元素测定。结果　下颌延长后两侧牵张间隙均有新骨形成,应用rhBMP-2的一侧牵张骨痂中的新骨组织比对照侧多而成熟,钙化程度较高。结论　基因重组人骨形成蛋白-2可能有促进兔下颌牵张成骨的作用。     

补肾壮骨中药对成骨质量和骨钙蛋白的影响

目的 探讨补肾壮骨中药对下颌骨牵张成骨的作用机制.方法 将16只英国小猎兔犬(beagle)随机分为中药组和对照组并行其右侧下颌骨劈开,植入常规组合式骨牵张器,经7d延迟后,以0.5mm每12h的速度连续牵张10d.中药组自牵张器植入术后第1天,口服补肾壮骨中药至试验结束.分别于固定后的1、2、3、4周,每组处死小猎兔...     

The expression of endogenous hydrogen sulfide signal during distraction osteogenesis in a rabbit model

The hydrogen sulfide (H₂S) signal system plays an important role in bone metabolism. However, the role of endogenous H₂S during distraction osteogenesis (DO) remains unclear. Sixty-two male New Zealand White rabbits were subjected to right mandibular DO. Before distraction, the animals were divided randomly into two groups: group A, 0.5 mm twice/day for 10 days; group B, 1.25 mm twice/day for 4 days. Plasma and distraction gap tissue were harvested to determine the H₂S signal. The osteogenesis effect was also evaluated. The newly regenerated bone in group A presented a higher level of mineralization and biomechanical strength than that in group B. The bone mineralization density in group A was 1.95-fold that in group B (P = 0.028), while the biomechanical strength in group A was 1.26-fold that in group B (P = 0.042) at the end of the experiment. The H₂S signal was detected during the whole process of DO. The relative plasma H₂S concentrations in group A were noticeably higher than those in group B at the middle of distraction (P < 0.001), at the end of the distraction (P = 0.034), and 2 weeks after the end of distraction (P = 0.002). The results suggest that the endogenous H₂S signal system plays a major role during DO.     

腺病毒介导的人骨形成蛋白2基因转染促进下颌牵张成骨的实验研究

目的探讨局部应用腺病毒介导的入骨形成蛋白2（adenovirus vectors containing human bone morphogenetic proteins 2, Ad-hBMP-2）对兔下颌骨牵张成骨的影响。方法24只新西兰大白兔随机分为实验组（12只）和对照组（12只），并建立下颌骨双侧牵张成骨模型。经过5d潜伏期后，以0．5mm／12h的速度牵张7d。固定期第1天，在实验组骨牵张区注射0．2ml滴度为10^12pfu／L的Ad-hBMP2，对照组骨牵张区注射0．2ml滴度为10^12pfu／L的腺病毒介导的增强型绿色荧光蛋白。在固定期第7、14、28天对下颌骨牵张区进行骨密度及新生骨量比较。结果Ad-hBMP-2治疗组牵张区骨密度及新生骨量明显高于对照组。结论腺病毒介导的人骨形成蛋白2具有促进兔下颌牵张成骨的作用。     

Bone regeneration in mandibular distraction osteogenesis combined with compression stimulation.

PURPOSE: This study compared modified distraction osteogenesis (DO) protocol with conventional DO protocol on healing bone formation. Computer simulation was performed to understand the mechanical environment of modified DO protocol, which applies compression during the consolidation period. MATERIALS AND METHODS: Fifty rats were used in this study. Twenty-five rats in the conventional DO (control) group were sacrificed at postoperative days 11, 21, 28, 35, and 49 after osteotomy. In the modified DO (experimental) group, compression was applied on day 7 after distraction (day 18 postoperatively) for 4 days during the early consolidation period and 25 rats were sacrificed on postoperative day 19, 28, 39, 46, and 53. The histologic and radiographic findings were used to compare the 2 groups. Further, computer simulation was used to predict the mechanical environment of healing bone under conventional and modified DO protocol. RESULTS: Radiographic findings showed that the experimental group resulted in denser and wider healing bone. Histologically, the experimental group yielded more mature lamellar bone than the control group. Computer simulation showed that absolute values of tissue strains were nearly double in the control group because of the softer healing tissues. Both the experimental and control groups showed high strains at the ridge crest. Concentrated tensile strain along the distraction direction at the ridge crest might hinder bone formation at the interface, while compressive strain could facilitate the process. CONCLUSION: This study proposed a modified DO protocol of adding compression during the early consolidation period of conventional DO protocol. This new technique appears to provide faster and denser bone regeneration.     

Microscopic changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible.

PURPOSE: Unilateral mandibular distraction osteogenesis (DO) has been shown to cause gross changes in the mandibular condyle and articular disc. The purpose of this study was to correlate histologic findings with these gross changes in a minipig distraction model. MATERIALS AND METHODS: Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0-day latency and rates of 1, 2, or 4 mm/day for a 12-mm gap. After the minipigs were killed (at 0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested, decalcified, prepared for standard paraffin embedding, and evaluated to determine changes in 1) morphology and thickness of the articular cartilage and subchondral bone and 2) morphology of the disc. RESULTS: In control animals, there were no degenerative changes in the articular cartilage and underlying condylar bone; there were no significant differences in the mean articular cartilage thickness. The temporomandibular joint discs were normal. In experimental animals, distracted condyles showed increasing degenerative changes and mean articular cartilage thickness as the DO rate increased. The discs were thinner. These changes were present, but to a lesser degree, in the contralateral condyles. After 90 days, degenerative changes in the condyles and discs were reduced, after remodeling, except in the 4 mm/day DO group. CONCLUSIONS: Histologic changes in the condyles and temporomandibular joint discs in response to mandibular DO correlated with previously reported gross changes. These changes were greater at higher distraction rates and remodeling back to normal occurred in mandibular condyles distracted at 1 mm/day.     

Preliminary investigation into the effects of electrical stimulation on mandibular distraction osteogenesis in goats

Craniofacial distraction osteogenesis (DO) was found to be a procedure with low preoperative and postoperative morbidity. Direct current electrical stimulation is used clinically to treat different orthopaedic problems. It provided a significant increase in new-bone formation, and a higher mechanical strength of healing.The purpose of this study was to test the effect of electric current on distraction osteogenesis and to establish the best period to apply an electric current during the different distraction phases.Twelve healthy adult goats were subjected to a vertical osteotomy in the symphyseal area. A distraction device was fixed to the bone. Animals were divided into two groups, Group I (three goats) and group II (nine goats). In group I, the device was activated 1mm per day for 10 days; while in group II, the device was activated 1mm per day for 10 days with the application of direct electric current stimulation of 10 microA either during the first 3 days of latency in a continuous mode (ESL group), or during the first 3 days of the activation period in a continuous mode (ESA group); or during the first 3 days of the consolidation period in a continuous mode (ESC group). After the activation period was completed, the distraction device left in place for additional 15 days for bone consolidation in all animals. Animals were then sacrificed, the mandible was harvested, and the distracted areas were removed and processed for mechanical and histological studies. The results of this study suggested that direct current electrical stimulation display synergism on mandibular distraction when this stimulation applied to the distraction zone during activation or consolidation periods.     

Comparison of different distraction rates in the mandible: an experimental investigation.

This study evaluated bone distracted in rabbit mandibles at different intervals and with different daily rates of distraction histologically with the goal of attaining a universally accepted distraction protocol. Osteogenesis was investigated in mandibles distracted at different rates in 24 New Zealand rabbits using a custom-made submerged distractor. Distraction was started on the third postoperative day for a total of 10 mm. The animals were divided into four groups each containing six rabbits. Group 1 was distracted 0.5 mm twice a day; Group 2 was distracted 1.0 mm once a day; Group 3 was distracted 1.0 mm twice a day and Group 4 was distracted 2.0 mm once a day. All the animals were sacrificed 6 weeks after completion of distraction. Half of the distracted mandibles were decalcified for H&E staining and polarized light microscopy studies. Sections of the undecalcified half of the samples were stained with Goldner's stain. The results indicate that a distraction rate of 1.0 mm per day produced the best osteogenesis among the tested rates. There was no great difference in osteogenesis between 1.0 mm once a day and 0.5 mm twice a day. However, 0.5-mm distraction may result in immature bone healing. Distraction of 1.0 mm twice a day resulted in incomplete osteogenesis, while distraction of 2.0 mm once a day resulted in fibrous union. It is clear from these results that a shorter period of device fixation should be achieved by methods other than rapid distraction.     

Changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible.

PURPOSE: Distraction osteogenesis (DO) is a commonly used technique for mandibular lengthening, but changes in the temporomandibular joint have not been well documented. The purpose of this study was to evaluate the effect of DO, at varying rates, on the mandibular condyle and articular disc. MATERIALS AND METHODS: Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0 day latency and rates of 1, 2, or 4 mm/d for a 12-mm gap. After the animals were killed (0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested and evaluated to determine changes in 1) condylar form and size, 2) condylar surface, and 3) the articular disc. RESULTS: Articular surfaces of the condyles in control animals were smooth, with no irregularities or erosions. In animals undergoing distraction, ipsilateral condyles showed increasing changes in morphology and AP dimension, and surface contour irregularities as the DO rate increased. These changes were present, but to a lesser degree, in the contralateral condyles. Articular discs of both ipsilateral and contralateral sides showed variable thinning at the medial aspect at end DO. After 90 days, changes in the condyles and discs were reduced by remodeling except in the 4 mm/d DO groups. CONCLUSIONS: Results of this preliminary study indicate that gross changes occur in condyles and discs after unilateral mandibular DO. These changes are more severe at faster distraction rates (4 mm/d) and tend to resolve during neutral fixation when a rate of 1 mm/d is used.     

Histomorphometrical analysis of new bone obtained by distraction osteogenesis and osteogenesis by periosteal distraction in rabbits

The aim of this study was to compare histomorphometrically the new bone tissue obtained using two different distraction methods, and evaluate these two methods in terms of their advantages and disadvantages. In 36 New Zealand adult male rabbits, divided into two groups, a gradual distraction was performed using a device placed on the lateral surface of the mandibular corpus. In one group osteotomy was not performed and osteogenesis by periosteal distraction (OPD) only was used. In the other group, conventional distraction osteogenesis (DO) was performed. After a 7-day latent phase, the same distraction protocol was applied to both groups. Each group of rabbits was further divided into three sub-groups killed on the 15th, 30th and 60th days of the consolidation period, and histological analysis was performed. The mean extent of newly formed bone tissue was 14.4 mm2 in the OPD groups and 25.4 mm2 in the DO groups. When compared statistically, there were significant differences between all the DO and OPD sub-groups. The newly formed bone tissue obtained by OPD was rich in interstitial fatty tissue. These results indicate that bone tissue newly formed by OPD is not suitable for occlusal forces.     

牙支抗羊下颌骨牵张成骨的组织学观察

目的：用自制的牙支抗骨延长装置进行羊下颌骨延长的实验研究，观察其组织学特征。方法：将9只7～9月龄山羊，实验组分4组，每组2只，对照组1只，在下颌第2和第3前磨牙之间行骨皮质切开术后，将自制的颌骨延长装置黏固于牙齿之上，术后5d开始加力，每次0．25mm，2次／d。在开始加力后分别于8、16、32、48d时将动物处死，标本进行四环素荧光标记检查、HE染色及Mallory三色染色观察。结果：四环素荧光标记结果显示：存延长区域内有黄绿色荧光标记的新骨形成；HE染色及Mallory三色染色结果显示：新骨从牵引区两侧逐渐向中央延伸，融合后的骨小梁逐渐改建成熟，纤维束、新形成的骨小梁以及早期的各种细胞均表现为长轴与牵引力的方向一致。结论：新骨有沿着牵引力方向形成与改建的组织学特点：     

The BMP signaling and its Smads in mandibular distraction osteogenesis

Aim:  The aim of the present study was to clarify the mechanism of signal transduction of bone morphogenetic proteins (BMPs) through their specific down signaling molecules Smads inducing bone formation in response to mechanical stimulus during distraction osteogenesis (DO) in the rat mandible.
Materials and methods:  Osteotomy of the left mandible was performed in 45 rats. Thirty rats underwent mandibular distraction (protocol; 5 days latency, 8 days distraction, and 2 weeks consolidation) while 15 rats served as non-distracted (fracture healing) group. The expression of BMPs-2,-4 and Smads 1, 5, and 8 were evaluated in the new regenerate area using immunohistochemistry.
Results:  Expressions of BMPs-2,-4 and Smads 1, 5, and 8 were moderate during latency, significantly increased during distraction and decreased towards consolidation period.
Conclusions:  The enhanced expression of BMPs and its Smads during distraction compared to the non-distracted group suggests the possible role of BMP signaling pathway in translation of mechanical forces into biological results during DO.