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。     

骨内型镁合金牵引器在犬牙槽骨垂直骨增量中的应用

背景：牙槽骨牵张成骨由于治疗周期长、二次手术创伤等限制了临床的广泛应用,镁合金作为可降解的生物金属材料可以制作成牵引器解决牙槽骨的软硬组织缺损问题。目的：探讨运用自行研制的骨内型镁合金牵引器垂直牵引犬下颌牙槽骨的可行性。方法：选取9只犬,拔除犬双侧下颌前磨牙,形成萎缩牙槽嵴模型。选取右侧下颌骨为实验侧,左侧为对照侧。3个月后选取右侧下颌骨行骨切开术形成输送盘,并植入1枚牵引器,1周后开始牵张,2次/d,每次0.5 mm,共6 d。固定期3个月后将犬麻醉处死并解剖下颌骨进行大体、X射线片、Micro-CT和组织学观察,并与对照侧进行比较。结果与结论：(1)9只犬除1只中途死亡并补足后,均成功完成牙槽骨的垂直增高,游标卡尺测量实验侧较对照侧增高4.94 mm;(2)X射线片检查发现牵张间隙消失,新骨密度增加;取出牵引器可见表面出现腐蚀、降解;(3)组织学检查可见实验侧活跃的成骨细胞和骨小梁结构,以及部分成熟的骨组织;(4)Micro-CT检查可见实验侧比对照侧骨小梁与牵张方向更一致(P <0.05);实验侧和对照侧相比骨小梁数目、厚度少量增加但无显著差异(P> 0.05),分离...     

人骨形态发生蛋白2基因修饰自体骨髓间充质干细胞移植促进兔下颌骨牵张成骨实验的组织形态学观察

背景：如何提高牵张成骨过程中新骨形成的速度和质量,缩短牵张成骨治疗时间,减少并发症的发生是目前该领域的研究热点。 目的：观察人骨形态发生蛋白2基因修饰自体骨髓间充质干细胞移植对兔下颌骨牵张成骨新骨形成的促进作用。 方法：36只新西兰白兔随机摸球法分为3组。建立牵张成骨动物模型,在固定期第2天,实验组于牵张间隙注射人骨形态发生蛋白2基因修饰的自体骨髓间充质干细胞;对照组注射等量自体骨髓间充质干细胞;空白组注射等量生理盐水。 结果与结论：在固定期2周及6周实验组牵张区骨小梁形成质量明显好于对照组和空白组。证实骨形态发生蛋白2基因修饰的自体骨髓间充质干细胞移植能有效促进兔下颌骨牵张成骨新骨形成。     

富自体浓缩生长因子膜在兔下颌骨牵张成骨中的作用北大核心

背景:富自体浓缩生长因子膜可参与调节代谢,已被用于骨缺损的重建。研究发现在牵张成骨的新骨缝附近的成骨细胞、间质细胞及骨细胞的胞质中均有骨保护素和核因子ΚB受体活化因子配体表达。目的:分析骨矫形作用的机制及富自体浓缩生长因子膜对兔下颌骨牵张成骨的促进意义。方法:随机选取24只大白兔建立兔下颌骨牵张成骨模型;对照组行左单侧下颌骨牵张成骨;实验组将富自体浓缩生长因子膜固定于牵张成骨器内侧面并且完全包绕牵张间隙,再行右单侧下颌骨牵张成骨;共延长6 mm。在固定期第1,7,14及28天分别处死动物,获取双侧下颌骨行组织学苏木精-伊红染色、免疫印迹法Western blot法和免疫组织化学检测核因子ΚB受体活化因子配体及骨保护素在新生骨中的表达情况;观察和对比两组间牵张间隙内成骨效果。结果与结论:牵引后第1,7,14天骨保护素表达的阳性细胞率和阳性面积百分比实验组均显著高于对照组(P<0.05或P<0.01);牵引后第1,14天核因子ΚB受体活化因子配体表达的阳性细胞率和阳性面积百分比实验组均显著高于对照组(P<0.05或P<0.01);Western blot法检测核因子ΚB受体活化因子配体/骨保护素比值对照组较实验组要高(P<0.01)。结果说明,富自体浓缩生长因子膜可促进兔下颌骨牵张成骨间隙内的新骨形成和矿化,说明富自体浓缩生长因子膜是促进下颌骨牵张成骨的有效手段。     

下颌骨节段性缺损修复组织工程中珊瑚支架残留率的研究

目的探讨骨髓基质干细胞(bone marrow stromal cell,BMSC)复合珊瑚修复犬下颌骨节段性缺损支架的残留率。方法体外扩增、成骨诱导培养犬BMSC,分别将第二代细胞复合珊瑚后植入犬自体右侧3cm的下颌骨节段性缺损,术后12周(n=6),32周(n=6)取材后分别通过Micro-CT检测和大体、组织学图像分析骨修复、支架残留率和生物力学修复强度。结果 Micro-CT检测和组织学图像分析均表明,BMSC-珊瑚组组织工程骨12周时支架残留率显著高于32周(P0.05),而新骨随材料降解逐步成熟;生物力学显示术后32周力学强度显著高于12周(P0.05)。结论自体成骨诱导BMSC复合珊瑚形成的组织工程骨可良好修复犬下颌骨节段性缺损,随时间延长材料逐步降解,组织工程下颌骨进一步成熟。     

富血小板血浆在兔下颌骨牵张成骨中的作用

目的探讨富血小板血浆对兔下颌骨牵张成骨的影响。方法将24只成年健康白兔随机分为2组,实验组在牵张期注射自体富血小板血浆于牵张间隙中,对照组不注射富血小板血浆。牵张结束后2、4、8周每组各处死4只动物取材,进行骨密度测量、组织学和扫描电镜观察。结果所有实验动物下颌骨均被成功延长7.0mm,牵张间隙中可见新骨组织生成与改建。同对照组相比,实验组新骨生成与矿化较快,牵张间隙中骨小梁分布密度及成熟度也较高。结论自体富血小板血浆对兔下颌骨牵张成骨可能有明显的促进作用。     

跟腱移植物与不同大小骨隧道匹配重建前交叉韧带

背景：前交叉韧带是维持膝关节稳定性的重要解剖结构,前交叉韧带重建后的腱骨愈合质量与临床功能康复一直备受关注。 目的：探讨在前交叉韧带重建术中采用相同直径的移植物与不同大小骨隧道相匹配,用组织学方法观察移植物肌腱与周围骨壁的愈合情况,同时用生物力学的方法检测其功能恢复情况。 方法：取犬自体中1/3跟腱作为前交叉韧带移植物,修整为相同直径4 mm。16只成年雄性杂交犬随机数字表法平均分配到4个组,完整切除前交叉韧带,于股骨和胫骨止点处分别制备胫骨、股骨隧道,直径分别为5,4.5,4,3.5 mm,并移植入待用跟腱链接于骨隧道内。重建后6周时,按常规麻醉处死实验犬,收集手术区域组织与器官,作解剖、苏木精-伊红染色组织学观察、生物力学检测及进行统计学分析。 结果与结论：前交叉韧带重建后6周,解剖观察移植物与骨隧道生长未见各组明显差异;苏木精-伊红染色发现腱骨愈合界面出现sharpey样纤维连接,3.5 mm骨隧道组胶原纤维较其他组致密有序;同时3.5 mm移植物生物力学检测结果优于同期各组。结果提示,在前交叉韧带重建中,减小与移植物匹配的骨隧道直径,使其肌腱与骨隧道之间紧密压配,能提供更加稳定的细胞生物学和力学环境,加快腱骨愈合界面的形成和改造,提高腱骨愈合质量。     

组织工程化骨修复犬牙槽骨缺损的组织学观察

目的观察组织工程化骨修复犬牙槽骨缺损过程中的新骨形成及其矿化程度。方法全麻及无菌条件下抽取犬胸骨骨髓,体外诱导培养犬自体骨髓间充质干细胞。取成年杂种犬8只,随机分成实验组和对照组,每组4只。实验组将已分化的自体成骨细胞与Bio-Oss骨胶原复合修复犬牙槽骨缺损:对照组牙槽骨缺损处仅植入Bio-Oss骨胶原。每组分别于术后4周,8周各处死2只动物,标本常规切片后行HE和改良Masson三色染色,光学显微镜下观察各组标本的组织学表现。结果实验组4周时即可见骨缺损修复区骨胶原内蓝色的新骨形成,随着时间的推移,形成新骨逐渐矿化成为红色的成熟骨组织,8周时骨缺损修复区可见大片新骨呈岛状或条索状排列,新生牙槽骨骨化效果明显优于对照组,Masson染色为红色。结论组织工程化骨促进犬牙槽骨缺损组织的修复。     

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      

犬下颌单侧不全截骨牵张成骨有限元模型建立与分析

目的:建立犬下颌单侧不全截骨牵张成骨有限元模型,观察牵张过程中,牵张侧和非牵张侧的位移情况。方法:犬下颌骨CT的DICOM数据经Mimics软件处理形成几何模型,经Magics软件切割、粘接等功能处理,建立有限元模型模拟犬下颌单侧不全截骨牵张成骨,观察当一侧下颌骨滑动骨块被牵开1mm,两侧特定标志点的位移情况。结果:建立了由五部分组成的犬下颌单侧不全截骨牵张成骨有限元模型,获得了当一侧滑动骨块被牵开1mm时,牵张侧和非牵张侧的位移云图。结论:牵引过程中当下颌骨滑动骨块移动1mm时,牵张侧和非牵张侧各标志点位移有不同程度的增加,但下颌关节处位移最小。     

Monoblock craniofacial internal distraction in a child with Pfeiffer syndrome: a case report

A 7-yr-old boy visited our surgical center with Pfeiffer syndrome type 1, presenting with macrocrania, broad big toe and thumb, exophthalmos, tongue protrusion, malocclusion with midfacial retrusion, mild respiratory difficulty due to minor upper airway obstruction, and developmental delay. He also exhibited anthrophobia with a passive character. The patient was treated with internal monoblock distraction osteogenesis to increase the intracranial and intraorbital volumes, and the nasal and pharyngeal airway spaces using two modular mid-facial internal distractors. For distraction, the latency period was 1 week, the daily activation of 1.0 mm was 20 days (total advancement 20 mm at the midline), and the consolidation period was 3 months. The follow-up computed tomography 12 months after surgery showed expansion of the brain and proper ossification in the distracted area. The patient also showed aesthetically good cranial contours, improved tongue and eyeball protrusion, no respiratory difficulty, and improved learning. We suggest that the internal distraction may last longer than an external type, resulting in a better bone fusion rate and successful expansion of craniofacial bones.     

富血小板纤维蛋白对下颌骨牵引成骨区RANKL表达的影响

目的　通过动物实验,研究应用富血小板纤维蛋白（Platelet-rich Fibrin,PRF）对兔下颌骨牵引成骨区核因子KB受体活化因子配体（receptor activator for NF-KB ligand,RANKL）的影响, 为临床研究与应用提供参考依据。 方法　在20只成年大耳白兔的一侧下颌骨前部行骨切开术,用牵引器延长一侧下颌骨4 mm,牵引间隙放置PRF膜;另一侧下颌骨行骨切开并安置牵引器,作为对照组,稳定期第1、7、14、21、28天,分别处死各组动物,取牵引区新生骨痂行组织学及RANKL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,免疫组织化学显色RANKL主要定位于骨髓基质细胞的胞浆中,其中以稳定期的第1,14天的表达最强。在稳定期第1、14天,实验组较对照组RANKL表达的阳性细胞率及阳性面积百分比差异有统计学意义（P＜0.05）,以后逐渐下降,第28 d仅有微弱表达。 结论　动物实验表明,PRF能促进兔下颌骨牵引成骨区新骨的生成,RANKL可能在牵引成骨过程中特别是调控组织细胞应力信号传递的早期发挥破骨作用。     

杜仲醇提取物对兔下颌牵张成骨的影响

背景：目前牵张成骨由于治疗周期长、并发症较多成为临床广泛运用的瓶颈,不能满足临床推广需要。 目的：以兔下颌骨牵张动物模型为实验平台,观察全身运用杜仲醇提取物对牵张新骨再生的影响。 方法：24只新西兰大白兔随机均分为对照组及实验组,建立兔下颌单侧牵张模型,牵张速率为每12 h 1 mm。在牵张期2次/d,实验组及对照组分别予以灌胃杜仲醇提取物及等量生理盐水,牵张结束后6周处死动物收集标本行成骨检测。 结果与结论：两组动物牵张间隙内均可观察到新骨生成。牵张成骨结束后6周下颌骨CT图像显示实验组兔牵张间隙舌侧骨皮质生成良好,颊侧骨皮质连续,牵张间隙可见均匀骨质生成桥接;下颌骨核素扫描显示实验组兔下颌骨牵张间隙表现为核浓集,强度明显强于对照组;X射线显示实验组牵张间隙完全桥接,新生成骨质密度均匀,可见上下侧骨皮质形成良好;Micro-CT图像显示实验组骨皮质部分形成较好,骨小梁分布较为均匀,骨小梁明显较对照组粗壮,对照组部分区域仍有囊性变;Micro-CT微结构参数检测显示实验组骨体积分数、骨小梁厚度、骨小梁数量和连接密度均显著高于对照组;组织学观察显示与对照组比较,实验组牵张间隙中有较为成熟的束状骨,骨小梁方向较为规律。实验结果显示全身运用杜仲醇提取物可有效促进兔下颌快速骨牵张的新骨再生。     

牙周膜牵引成骨快速远中移动尖牙的可行性

背景：牵引成骨应用于患者的尖牙远中移动,能大幅度提高牙齿的移动速度,同时保护磨牙支抗。但关于牵引的速率、尖牙的牙髓活力、尖牙的牙周组织改建及该技术的生物学机制目前研究甚少。 目的：在成人患者中,评估使用牙周膜牵张成骨快速远中移动尖牙的可行性,同时监测牙髓活力、牙根吸收及尖牙牙周组织改建情况。 方法：选取9例成年错牙合患者,拔除上颌两侧第一双尖牙,通过改良牵张装置快速远中移动尖牙至预定的位置。利用头颅定位片及根尖片测量尖牙远中移动距离、支抗丧失、根尖吸收及牙槽间隔改建情况;并监测尖牙的牙髓及牙周情况。 结果与结论：通过牙周膜牵张成骨能在12-16 d内快速远中移动上颌尖牙至预定位置,尖牙远中移动7.18 mm 及远中倾斜(13.24±2.87)°;支抗丧失为0.5 mm;未见明显根尖吸收及牙周组织丧失;尖牙的牙髓活力在牵引后迅速下降,但3个月后明显恢复。结果显示牙周膜牵引成骨可显著加快尖牙移动速度,缩短矫治时间,同时保护磨牙支抗;未见牙根明显吸收、牙齿松动、牙髓坏死及牙周组织丧失等不良反应。提示牙周膜牵引成骨能够快速有效移动尖牙。     

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.     

The effect of low intensity pulsed ultrasound on regenerate bone in a less-than-rigid biomechanical environment

The purpose of this study was to investigate effects of low intensity pulsed ultrasound (LIPU) on distraction osteogenesis in a less-than-rigid biomechanical environment in a rabbit model. A less-rigid mini-lengthener was applied and a mid-tibial osteotomy performed in 20 New Zealand White rabbits. After a 7 day latency period, the tibiae were distracted 0.5 mm every 12 hours for 10 days. Ten of the rabbits received LIPU for 20 min/day (ultrasound group) and 10 received sham LIPU (control group) from day 17 until sacrifice on day 37. Radiographs were taken weekly after distraction and the callus area was measured. After sacrifice, dual-energy X-ray absorptiometry (DEXA), torsional testing to failure, and histomorphometry were performed. On radiographs, all the treatment tibiae displayed persistent radiolucencies; however, only one of the control tibiae displayed a radiolucent interzone. Torsional strength of the treatment group was 54% of the contralateral tibia compared to 139% in the control group (p<0.008). Bone density and callus size were not significantly different between the 2 groups; however, the ultrasound group displayed a tendency towards more cartilage and fibrous tissue formation (p<0.16) and less bone (p<0.16) than controls. In a biomechanically unstable environment, LIPU appears to stimulate more cartilage formation in regenerated callus than in controls. This callus is biomechanically inferior to unstimulated callus at the early stage of healing tested. During distraction osteogenesis a sound biomechanical environment is important to achieving anticipated results.     

Expression of neurotrophins and their receptors tropomyosin-related kinases (Trk) under tension-stress during distraction osteogenesis

The localization and expression of neurotrophins and their receptors during distraction osteogenesis was investigated in 72 male rat femurs (11 weeks old) to further clarify the concurrence of cellular and molecular events of new bone formation. After osteotomy, a 7-day lag phase was followed by distraction at the rate of 0.25 mm/12 h for 21 days (distraction phase), and a 7-day consolidation phase. The localization of neurotrophins (NGF, BDNF and NT-3) and their receptors tropomyosinrelated kinases (TRKA, TRKB and TRKC) by immunostaining showed positive staining in bone forming cells in each stage, although the presence and staining intensity varied by cell type and phase. The expressions of NGF, BDNF and NT-3 by real-time polymerase chain reaction (real-time PCR) showed that the peak of the mRNA expression of NGF occurred 10 days after distraction. NT-3 increased during bone extension, but decreased when distraction stopped. In contrast, BDNF continued to increase gradually throughout the distraction and consolidation phases. These findings suggest that neurotrophins and their receptors may play different roles in endochondral and intramembranous ossification in distraction osteogenesis. The tension stress caused by distraction may stimulate the expression of neurotrophins and their receptors, and promote osteogenesis.     

Wnt/β-catenin signaling is required for distraction osteogenesis in rats

Overview: The Wnt signaling pathway plays crucial roles in embryonic skeletal development and postnatal bone regeneration. However, mechanisms of Wnt signaling functioning in distraction osteogenesis (DO) haven’t been well characterized. Materials and Methods: We established a DO model using Sprague–Dawley rat tibia. And a Wnt signaling blocking agent, recombinant rat Dickkopf-related protein 1 (rrDkk1), was locally applied in the distracted gap to study the role of Wnt signaling during DO process. Animals in the experimental group received rrDkk1 injections (dose = 25 μg/kg) once daily during distraction period and every third day during consolidation stage (n = 48). Animals in the control group received saline under the same injection strategy (n = 48). Animals at different time points during DO process (1, 3, 6, 12 days after distraction, 10 days and 6 weeks after consolidation) were killed and tissues in the distraction region were harvested for radiography, dual energy X-ray absorptiometry, micro-computed tomography (micro-CT), and histological analyses. Results: Most Wnt ligands, cofactors, receptors, and antagonists were widely expressed in the distraction callus and were significantly upregulated during DO process. After rrDkk1 administration, the majority of these factors were downregulated at the mRNA level, except sFRP and GSK-3β. At the protein level, both β-catenin and Lef-1 were also suppressed by rrDkk1. In the long term, restricted bone healing was observed in the distracted callus in the rrDkk1 injection group. These findings were confirmed by histological and micro-CT analyses. Conclusions: Our findings suggest that Wnt signaling participates in the process of DO, and clinical therapeutic approaches of DO may do well to avoid Wnt pathway suppression.