牵张成骨修复兔下颌骨缺损中血管生成素-1的表达及意义

目的探讨血管生成素(Ang)-1在牵张成骨修复兔下颌骨缺损中的时空表达及生物学意义。方法对24只大白兔行单侧下颌骨缺损牵张成骨术,分别在延迟期末、牵张中期、牵张期末、固定期第12、、35、、7周末各处死3只动物,取牵张区骨痂,采用组织学和免疫组化法观察微血管生成以及Ang-1的表达变化。结果下颌骨牵张区主要以膜内成骨方式成骨,在牵张区内有明显的血管生成及较明显的Ang-1的表达。在新生血管管周前成骨细胞和成骨细胞中可见Ang-1的表达。非应力区(缺损区)以软骨内成骨为主,在肥大的软骨细胞中存在Ang-1弱表达。结论牵张力所产生的机械刺激可以导致牵张区中微血管和骨组织的生成,而Ang-1可能在牵张区新生血管的形成及稳定和新骨形成中起重要作用。     

Correlation of immunohistochemical characteristics of the craniomandibular joint with the degree of mandibular lengthening in rabbits.

PURPOSE: This study examined immunohistochemical changes in the craniomandibular joints of rabbits after distraction osteogenesis following mandibular corticotomy. MATERIALS AND METHODS: The experimental animals (n = 8) were divided into 3 groups that underwent 2, 3.5, and 5 mm of unilateral distraction osteogenesis (groups 1, 2, and 3, respectively). After corticotomy of the left mandibular body and a 7-day healing period, a second operation was performed to expose the device. Distraction was then performed at the rate of 0.5 mm/d. A 14-day consolidation period was allowed after the distraction was complete. Changes in cartilage, osteoblast activity, and osteoclast activity were then examined. RESULTS: The differentiation and proliferation of cartilage increased in groups 1 and 2, were highest in group 2, and decreased in group 3. Group 2 also showed the greatest increase in the width of the hypertrophic chondrocyte layer. Relative to the control group, osteoclast activity was only somewhat higher in groups 1 and 2 but was significantly higher in group 3. Osteoblast activity was significantly higher in groups 1 and 2 than in the control group. However, the osteoblast activity in group 3 was slightly lower than that in group 2. At the time of unilateral mandibular distraction, no degenerative changes of the temporomandibular joint were observed in groups 1 or 2, but bone resorption was observed in group 3. CONCLUSIONS: The unilateral mandibular distraction of 2 or 3.5 mm was acceptable in that no degenerative changes of the temporomandibular joint were observed on either the distraction or the nondistraction sides. Five millimeters of distraction might be beyond physiologic limits.     

成纤维细胞生长因子对兔下颌牵张成骨的影响

目的 研究局部应用碱性成纤维细胞生长因子（bFGF)对兔下颌牵引张成骨的影响。方法 成年大耳白兔8只，随机分为A、B两组，每组4只。用自行研制的牵张器延长双侧下颌骨6mm，用bFGF（20ng/ml）注入A组动物的牵张区，不注射bFGF的B组动物作为对照。在牵张结束后4周处死所有动物，取双侧下颌骨标本进行X线和组织学检查。结果 组织学分析结果显示，局部给予bFGF的A组动物下颌牵张后新骨生成速度和数量优于B组动物。结论 外源性导入碱性成纤维细胞生长因了可能有促进下颌牵引张成骨的作用。     

Histological evaluation of the temporomandibular joint after bilateral vertical ramus mandibular distraction in a canine model

The aim of this pilot study was to histologically evaluate the effect of bilateral vertical mandibular distraction osteogenesis (DO) on the temporomandibular joint (TMJ) in a canine model. Eight male beagle dogs underwent DO, with the placement of single-vector internal distractors. One unoperated animal served as control. After a latency period of 7 days, distraction was performed at a rate of 1 mm a day for an average of 12 days. The animals were divided into two groups (n = 4) and sacrificed after one or two months of consolidation. Eighteen TMJs were prepared for histological evaluation. Control TMJs surfaces were smooth, with no irregularities and trabecular bone was thick and multiply connected. In the one-month group, thinning of the trabecular bone was evident. The trabeculae were long, not multiply connected, parallel to each other and perpendicular to the articular surface. Although overall fibrous-cartilaginous tissues covering the TMJs were maintained with no signs of degenerative changes, one condyle from the one-month group had depressions and erosions of the fibro-cartilage layer and subcortical bone. In the two-month group, overall bone and cartilage architecture was more similar to the control specimens. This study indicates that, in the short term, gross changes can occur in the TMJ after bilateral mandibular vertical ramus distraction. These changes seem to be a process of biological adaptation to the pressure and functional changes secondary to surgery and distraction. However, long-term studies are needed to confirm whether the changes are completely reversible.     

Expression of bone morphogenetic proteins during mandibular distraction osteogenesis in rabbits.

PURPOSE: We examined the expression pattern of bone morphogenetic proteins (BMPs) during mandibular distraction osteogenesis in rabbits and also investigated the mechanism of membranous bone distraction. MATERIALS AND METHODS: Twenty-three rabbits underwent mandibular distraction (protocol; no latency period, a 1-week distraction at 0.5 mm/d, and a 2-week consolidation period). Samples were collected at 3, 5, and 7 days of distraction and at 1-week and 2-week consolidation. We prepared undecalcified fresh-frozen sections and immunohistochemically evaluated the expression of BMPs 2 through 8. RESULTS: Both endochondral ossification and intramembranous ossification were observed. The expression of BMPs 2, 4, 5, and 6 was observed continuously from the beginning of distraction. BMP-7 was expressed weakly. The expression of BMP-3 was not observed conspicuously during distraction but was strongly expressed at 1- and 2-week consolidation. CONCLUSION: The expression pattern of BMPs during membranous bone distraction was similar to that during long bone distraction, but it differed from the expression pattern of long bone distraction in that the expression of BMPs was maintained for 2 weeks after the completion of distraction.     

Changes in the temporomandibular joint after mandibular lengthening with different rates of distraction

This study assessed the changes in the condyle after mandibular lengthening with 2 different rates of distraction (1 mm/day and 2 mm/day). Unilateral mandibular distraction was performed in 8 young adult goats. The animals were sacrificed 8 weeks after the completion of distraction, and the temporomandibular joint (TMJ) specimens were harvested and processed for histologic examination and histomorphometric analysis. Adaptive changes in the condyle were observed in the goats distracted at a rate of 1 mm/day, whereas degenerative alterations were found in those distracted at a rate of 2 mm/day. This study suggests that the TMJ is able to withstand the impact of distraction at a rate of 1 mm/day, but more rapid distraction may induce degeneration in the condylar cartilage.     

Cartilage changes link retrognathic mandibular growth to TMJ disc displacement in a rabbit model

Recent experimental research demonstrated that non-reducing temporomandibular joint (TMJ) disc displacement in growing rabbits impaired mandibular growth. TMJ disc displacement is also shown to induce histological changes of the condylar cartilage. The authors hypothesized that the severity of these changes would correlate to the magnitude of mandibular growth. Bilateral non-reducing TMJ disc displacement was surgically created in 10 growing New Zealand White rabbits. Ten additional rabbits constituted a sham operated control group. Aided by tantalum implants, growth was cephalometrically determined for each mandibular side during a period equivalent to childhood and adolescence in man. At the end of the growth period, histologically classified cartilage features were correlated with the assessed ipsilateral mandibular growth. Non-reducing displacement of the TMJ disc during the growth period induced histological reactions of the condylar cartilage in the rabbit model. The severity of cartilage changes was inversely correlated to the magnitude and the direction of mandibular growth, which resulted in a retrognathic growth pattern.     

rhBMP-2对兔下颌骨牵引成骨区骨保护素表达的影响

目的：通过动物实验,研究应用外源性rhBMP-2对兔下颌骨牵引成骨区骨保护素（osteoprotegerin,OPG）的影响。方法：在48只成年大耳白兔的一侧下颌骨前部行骨切开术,分别将空白胶原、rhBMP-2 1.5mg胶原复合物植入下颌骨切开处,用牵引器延长一侧下颌骨4mm,稳定期第1、3、7、14天,分别处死各组动物,取牵引区新生骨痂行组织学及OPG免疫组化染色。结果：下颌牵引延长后牵引间隙均有新骨形成,应用rhBMP-2 1.5mg效果好。免疫组化染色OPG主要定位于成骨细胞的胞浆中。在同一时间内,应用rhBMP-2组较对照组有显著性差异（P〈0.05）。结论：动物实验表明,rhBMP-2能促进兔下颌骨牵引成骨区新骨的生成。     

Temporomandibular joint bony ankylosis: comparison of treatment with transport distraction osteogenesis or the matthews device arthroplasty

Temporomandibular joint (TMJ) bony ankylosis with micrognathia is a rare congenital condition that is difficult to treat and may result in recurrence. In a series of affected patients, we compared two new methods of treatment: transport distraction osteogenesis and Matthews Device arthroplasty. All patients had computed tomography scan documented bilateral TMJ bony ankylosis. Group I (transport distraction osteogenesis) underwent distraction advancement of the mandible (for micrognathia) followed by resection of the condyles, recontouring of the glenoid fossas with interposition temporoparietal-fascial flaps, and transport distraction osteogenesis of mandibular rami segments. Group II (Matthews Device arthroplasty) underwent all of the above procedures except for transport distraction osteogenesis. Instead, the Matthews Devices were anchored to the temporal bone and mandibular rami. Hinged arms allowed for motion at the reconstructed TMJ. In both groups, patients underwent extensive postoperative therapy. Preoperative, postoperative, and follow-up lateral cephalograms were obtained, and incisor opening distances were recorded. All patients but one had severe micrognathia (n = 9). For group I (transport distraction osteogenesis), mean age was 6.8 years. and mean advancement was 28.5 mm. For group II (Matthews Device arthroplasty) mean age was 8.2 years, and mean advancement was 23.5 mm. In group I (transport distraction osteogenesis), mean incisor opening was 1 mm preoperatively and 27.5 mm postoperatively; however, it relapsed to 14.3 mm by 12.5 months follow-up (48% relapse). Mean incisor opening in group II (Matthews Device arthroplasty) was 3.9 mm preoperatively and 33.4 mm postoperatively and remained at 30.6 mm after 11.1 months follow-up (8% relapse). One patient in group I (transport distraction osteogenesis) underwent surgical revision because of relapse. Our data showed that for congenital TMJ bony ankylosis both transport distraction osteogenesis and Matthews Device arthroplasty techniques were successful initially; however, the Matthews Device arthroplasty avoided long-term relapse.     

局部应用胰岛素样生长因子对下颌牵张成骨的作用

目的 研究局部应用外源性胰岛素样生长因子-I（IGF-I）对兔下颌牵张成骨的影响。方法 成年大耳白兔6只,随机分为A、B两组,每组3只。在兔双侧下颌骨前部行骨切开术,以IGF-I与I型胶原膜的复合物和单纯I型胶原膜分别应用于A、B两组动物的骨切开区域,用自行研制的牵张器延长双侧下颌骨6mm,在牵张结束后第4周处死动物,取双侧下颌骨标本进行X线和组织学检查。结果 两组动物下颌牵张后新骨生成速度和数量未见显著性差异。结论 外源性导入胰岛素样生长因子-I未见有明显促进兔下颌牵张成骨的作用。     

丹参酮Ⅱa磺酸钠对兔下颌骨牵张成骨促进作用的研究

目的：探讨丹参酮Ⅱa磺酸钠注射液对兔下颌骨牵张成骨的作用。方法：将12只大耳白兔随机分为对照组和实验组,建立单侧兔下颌骨牵张成骨模型,实验组自牵张期开始每日注射丹参酮Ⅱa磺酸钠注射液3mL,并分别于固定期1周、4周、7周各处死2只对照兔和2只实验兔,对标本进行大体观察、X线观察、组织学观察和骨组织计量学观察。结果：实验组动物牵张间隙内新骨形成速度及质量均优于对照组,实验组成骨细胞活跃,骨小梁较成熟,单位面积内成骨细胞个数及骨小梁面积百分比均高于对照组。结论：丹参酮Ⅱa磺酸钠对兔下颌骨牵张成骨过程具有促进作用。     

牵张成骨延长一侧下颌骨对颞下颌关节的影响

目的：研究牵张成骨（DO）延长一侧下颌骨对双侧颞下颌关节（TMJ）的影响。方法：用DO技术将8只山羊的一侧下颌骨延长10mm，在牵张完成后第8和16周分别处死4只动物，取双侧关节作组织学和扫描电镜研究。结果：下颌一侧DO术后双侧髁状突发生适应性改建，髁突表面超微结构正常。结论：在适当的牵张条件下延长一侧下颌骨不会对TMJ造成病理性损害。     

Orthodontic spring guidance of bilateral mandibular distraction in rabbits.

Although distraction osteogenesis can lengthen congenitally small mandibles, the distraction procedure can be difficult to control. To study the efficacy and safety of orthodontic spring guidance on bilateral mandibular distraction, an 8-mm anterior open bite was experimentally produced and corrected during bilateral mandibular distraction in rabbits. Orthodontic springs were attached to the anterior maxilla and mandible to redirect an ongoing distraction procedure. Sixteen rabbits underwent mandibular distraction: 6 rabbits received heavy springs (8 oz), 6 rabbits received light force springs (2 oz), and 4 rabbits served as control animals with anterior open bites without spring guidance. Nickel-titanium springs were applied during the last week of osseous distraction and the first week of consolidation. Distractors were left in place throughout a 2-month consolidation period. None of the animals developed fibrous union as a result of spring guidance. The 8-mm open bite did not close in the control group or in the light spring group after 2 weeks of spring wear or during the consolidation period. Heavy springs completely closed the experimental open bites within 2 weeks (P <.01, analysis of variance). Bite corrections did not change during the consolidation period. This study indicated that the addition of an orthodontic spring to a mandibular distraction procedure did not impair bone healing. With the distraction device in place, heavy spring forces redirected an ongoing mandibular distraction procedure and corrected an open bite, distraction side effect. Direct measurements, radiographic measurements, and tissue histologic factors described changes in segment position and shape of the distraction site.     

Modified bimaxillary distraction osteogenesis: a technique to correct facial asymmetry

AIM: To study the efficacy of modified simultaneous maxillary-mandibular distraction to correct facial asymmetry in patients with compensated occlusion and a canted occlusal plane. PATIENTS AND METHODS: During the period January 1998-December 2003, 15 patients with facial asymmetry (8 male and 7 female, mean age 18 years) were treated using a modified technique of simultaneous maxillary-mandibular distraction. Their facial deformities were caused by hemicraniofacial microsomia (n=6) or ankylosis of the temporomandibular joint (TMJ) (n=9). RESULTS: The mean (range) gain in mandibular height was 16 (13-22) mm, and increase in elongation 14 (11-18) mm achieved over 11-22 days. Predicted movement on cephalometric analysis correlated closely with the actual distraction (mean accuracy 0.4mm). CONCLUSION: Simultaneous bimaxillary distraction osteogenesis is a robust technique that provides the surgeon with the ability to correct facial asymmetry in patients with hemicraniofacial microsomia and those with facial deformity after ankylosis of the TMJ. A cephalometric prediction tracing made before distraction is a reliable guide to the actual distraction needed to correct the facial deformities in these patients.     

下颌骨牵引成骨与直接延长术的组织学比较

目的：通过对下颌骨牵引成骨与直接延长术组织学变化的对比研究分析，探讨牵引成骨的成骨机制。方法：24只狗随机分为牵引成骨组和直接延长组各12只，用HE染色光镜组织学检查方法分别观察牵引第6天、牵引后固定2、8周不同时期的两组组织学变化。结果：牵引组在牵引后固定第8周，牵引区几乎完全由新生的骨组织连接修复，成骨方式是以膜内成骨为主，伴有少量的软骨内成骨；而直接延长组仅早期在两骨断端附近可见活跃的膜内成骨，两周以后则以软骨内成骨为丰，中间区域仍为大量的纤维结缔组织，8周以后成骨量增加．但中央仍为软骨组织和纤维组织间隔。结论：牵引成骨以膜内成骨为主，达到良好的骨愈合，直接延长成骨效果不稳定，容易导致成骨不良。     

应用钛镍记忆合金牵张成骨增高下颌牙槽嵴的初步研究

目的 探讨应用钛镍记忆合金牵张成骨增高下颌牙槽嵴的可行性。方法 选用成年杂种犬10只，拔除两侧下颌全部前磨牙和第1磨牙，实验组1个月后用完全埋置的钛镍记忆合金牵张器完成牵张手术。在牵张手术前及术后1、5、13周测量术区颌骨高度，拍X线片，分别在牵张完成后1、3个月处死动物，进行组织学研究。结果 牵张器就位后骨块即开始牵张升起，术后1周达7．5～11．5mm，其后无明显变化。X线片可见牵张完成后1个月牵张区骨密度增高，有新骨生成；3个月骨密度与周围牙槽骨接近。组织学观察牵张区早期有胶原束形成，随后钙化成骨。结论 用钛镍记忆合金牵张器可成功牵张增高犬下颌后牙区牙槽嵴，新骨以膜内成骨方式生成。     

Intraoral distraction osteogenesis for the correction of facial deformities following temporomandibular joint ankylosis: a modified technique

The aim of this study was to evaluate the feasibility of transoral bimaxillary distraction osteogenesis before releasing temporomandibular joint (TMJ) ankylosis using intraoral mandibular distractors. Nine patients (5 males, 4 females) aged 14-35 (mean 19) years were included. A bilateral Le Fort I osteotomy was performed together with a mandibular osteotomy on the affected side(s). An intraoral distractor(s) was inserted in the lower jaw, followed by an intermaxillary fixation (IMF) to maintain preoperative dental occlusion. The distractor was activated, after a latency period of 5-7 days, 2 times daily by 0.5 mm. There followed a consolidation period of 6-8 weeks. TMJ ankylosis was then released via a peri-auricular incision, a gap arthroplasty was performed, and mandibular movement was established after removal of the IMF and distractor. Optimal results were achieved clinically and radiologically with minimal relapse and complications. Apart from minor complaints, the distraction process was smooth and tolerable in all cases. Total mandibular elongation ranged from 17 to 25 mm (20.7 mm). Occlusal canting decreased to 0 degrees in 7 patients and to 1 degree in 2 patients (mean 0.2 degrees). After a mean follow-up period of 17 months, a mean postoperative mouth opening of 34.7 mm was achieved (0.6 mm preoperatively) and no re-ankylosis was detected. Intraoral distraction of a deformed mandible and maxilla before releasing TMJ ankylosis is a feasible and perhaps advantageous technique.     

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。     

下颌骨牵张成骨对下牙槽神经影响的实验研究

目的　观察狗双侧下颌骨牵张成骨术中不同时间点的下牙槽神经的电生理功能及组织学结构的变化。方法　实验组 :12只狗行保留下牙槽神经的双侧下颌骨截断术 ,装上自制的口内牵张器 ,于术后第 8天开始牵张 ,1mm/d ,共 10d ,牵张长度约 10mm。分别在牵张中第 6天、牵张完毕后固定 2周及 8周时各处死 4只动物。分别在术前及术后的不同时期用电生理方法检测双侧下牙槽神经的传导功能 ,并于处死前取出双侧下牙槽神经进行组织病理学及超微结构组织学检查。对照组 :4只狗 ,其中 2只狗作为对照组 ,未行手术 ;另 2只狗为手术对照组 ,进行与实验组相同的骨切开截断术 ,上牵张器 ,但未行牵张和固定 ,于操作完毕时取出双侧下牙槽神经作为术后的组织学结构标本。结果　实验组动物的下牙槽神经在光镜下显示部分神经纤维稍肿胀变粗 ;电镜下显示部分神经纤维髓鞘的板层松解及脱髓鞘现象 ;电生理结果显示 ,神经传导的速度于截断术后的不同时期均低于术前 ,但仅术后第 8天 (即牵张前 )的传导速度与术前的传导速度差异有显著性 (P <0 .0 1)。结论　对狗的双侧下颌骨进行牵张成骨时 ,可一过性引起下牙槽神经损伤。其损伤的主要原因是手术过程所致。在适当的牵张速率、牵张长度和牢固的固定条件下 ,下颌骨的牵张成骨术对下牙槽 还原。     

Effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone consolidation on distraction osteogenesis: a preliminary study in rabbit mandibles.

AIM: To examine the effectiveness of administering recombinant human bone morphogenetic protein-2 (rhBMP-2) in distraction osteogenesis. MATERIAL AND METHODS: Twenty-one mature male Japanese white rabbits underwent unilateral mandibular osteotomy. After 5 days, the osteotomized mandibles were distracted 1mm/day for 10 days. On the first day (groups A-1 [n=4] and A-2 [n=4]) or on the last day (group B [n=5]) of distraction, rhBMP-2 mixed with collagen gel was injected into the distraction zone. In control groups (groups C-1 [n=4] and C-2 [n=4]), the mandibles were distracted without rhBMP-2 injection. At the end of the distraction period (groups A-1 and C-1) and after 2 weeks of consolidation (groups A-2, B, and C-2), the distracted mandibles were harvested and examined with soft radiographs, peripheral quantitative computed tomography (pQCT), and microscopy. RESULTS: Radioopacity was more marked in the distraction zone of the groups with rhBMP-2 than in control groups. The mineral density of the cortical bone (BMD) was higher in groups B and A-2 than in group C-2. Histologically, bone formation was more advanced in groups A-2 and B than in group C-2. The cortical BMD was higher in group A-1 than in group C-1. Histologically, bone formation was more advanced in groups A-2 and B than in group C-2. CONCLUSION: These results suggest that rhBMP-2 promotes bone formation in distraction osteogenesis.