【作者】 丁金勇；

【导师】 周跃；

【作者基本信息】 第三军医大学 ， 外科学， 2009， 博士

【摘要】 背景和目的20世纪50年代,Cloward首先提出后路腰椎间融合术的概念,从生物力学分析,这是一种较为理想的脊柱融合术,PLIF逐渐发展成为脊柱外科基本技术之一。自DeBowes将不锈钢篮(cage)植入马的颈椎获得愈合,到Bagby1988年将cage应用于人体颈椎间融合,在以后的几十年里,椎间融合器在生物力学方面的优越性越来越受到关注,新的设计理念不断引入,技术不断改进,材料不断更新,呈现出较快的发展态势。椎间融合器的外形由早期的带螺纹中空圆柱体状cage,到直立型网状cage,再到长立方体形。这类cage中空,四周开孔,内部填充骨屑,平放椎间隙内,上下面有不同形状的锯齿,以防前后滑动。近年来其发展较快,出现了多种变化,如借鉴人工假体的设计,将cage四周进行表面喷涂,或改为实心设计,表面喷涂羟基磷灰石(HA),利用涂层的微孔结构,有利于骨组织长入;cage的形状更适应椎间隙的解剖形态,如带有弧度的肾形,材料采用可降解材料,这类cage的优点是弹性模量与推体皮质骨接近,具有长期的生物相容性和优良的抗疲劳性,可通过X线。总之,cage的材料已经从最初的惰性材料钛合金发展到可降解、可吸收生物活性材料。近年来,异体皮质骨材料的cage也己经出现,但因为材料来源、储存费用增加等因素限制了它的发展。Cage行腰椎间融合的植入方式包括:(一)后路腰椎间融合,PLIF自问世以来,一直作为椎间融合的首选,是因为前路手术固有的潜在的血管、脏器、或植物神经损伤一直为人们关注;另外,如果存在椎间盘退变、小关节增生、后纵韧带钙化、侧隐窝和椎管狭窄等病理改变,前侧入路难以解决全部问题,PLIF允许减压、融合、固定一次完成。(二)前路腰椎间融合,自Obenchain报道ALIF技术以来,人们对它的认识不断深入,90年代中期开放式ALIF的手术途径多采用腹膜外入路,随着内窥镜技术的发展,采用经腹腔途径的腹腔镜下L4/5,L5/S1椎间融合获得发展,相关的解剖和临床研究增加。(三)后外侧腰椎间融合,在PLIF的基础上发展、演变而成,包括经椎间孔腰椎间融合和后外侧斜行单枚cage腰椎间融合。腰椎椎体间融合虽然已经被广泛应用,但传统的腰椎椎体间融合手术需要广泛剥离肌肉及长时间的牵引,易致软组织损伤。椎旁肌肉的病理改变是腰椎手术后腰部力量减弱及慢性腰痛发生的原因,微创下的腰椎椎间融合手术可避免椎旁软组织的过度损伤,减少术中出血、减轻术后疼痛,缩短住院时间,患者易接受。目前微创腰椎椎间融合术无论从观念上和技术上均有了很大的发展,主要有以下几种方法:一、腹腔镜下前路ALIF,包括经腹膜和腹膜后腹腔镜下ALIF两种方式。经腹膜腹腔镜下ALIF,自Obenchain在1991年报道了第1例腹腔镜下腰椎间盘切除术后,腹腔镜下ALIF逐渐开展起来。腹膜后腹腔镜下ALIF技术可用于L1~S1节段腰椎病变,克服了经腹膜腹腔镜局限于L4~S1的限制。二、前路小切口ALIF,前路小切口ALIF为传统开放手术的改良术式,根据腹部大血管分叉水平选择前正中切口或右下腹斜切口,可经腹膜或腹膜后入路,用特制的自动牵开器牵开腹膜内器官组织,大血管用拉钩牵开,暴露病变椎间盘,切除椎间盘后置入融合器。三、内窥镜下后路腰椎椎体间融合和经椎间孔腰椎椎体间融合,TLIF和PLIF都可以通过扩张套管小切口完成。四、经骶前间隙轴向腰椎间融合,Cragg等首先报道经骶前间隙入路可行轴向L4~L5、L5~S1轴向融合、其后该方式获得了发展并正式用于临床进行L5~S1轴向融合。融合器在腰椎融合手术可以发挥良好的力学支撑作用并可有效提高椎间融合率。随着微创脊柱外科椎间融合技术大量开展,椎间融合器在腰椎手术中得到广泛的应用。微创TLIF是在一个直径有限的工作管道下完成的,开放手术使用的融合器由于体积较大,不利于微创手术应用,无法直接用于微创手术,能否设计一种小巧的新型微创融合器,既能满足微创的手术需求,又能在开放手术中应用呢?基于以上设想,我们课题拟用聚醚醚酮设计制造出组合式多用腰椎间融合器,通过体外计算机模拟有限元力分析,新型融合器自身力学强度、刚度分析,安装新型融合器后的脊柱功能节段力学性能测试,在动物体内融合实验,对其进行临床前期力学和性能测试,为进一步加以改进和临床应用提供基础。方法一、参考目前国内外椎间融合器的相关文献,设计出组合式多用腰椎间融合器,并与公司合作生产出产品。二、新型组合式多用腰椎间融合器的实验研究1.新型组合式多用腰椎间融合器的有限元分析首先取32岁健康男性自愿者的腰椎(新桥医院放射科)进行扫描,通过工作站将扫描获得的图像导入计算机中,先建立几何实体模型后再划分网格单元,在其固有的三维坐标系中建立腰椎间盘的几何模型。接下来建立植入新型椎间融合器有限元脊柱模型,融合器的大小按椎间隙空间选择,能够恢复椎间盘高度和脊柱的前凸。参考以往文献数据,进行有限元模拟力学加载。垂直轴向压缩力为500N,扭力为15牛米。模拟在两个模型上进行,施以相同的界限条件,载荷连续的加载至腰3的上终板,同时下边腰4的终板被固定,模拟腰椎的前屈、后伸、左右侧屈和旋转运动。最后提取腰椎在植入新型组合式腰椎间融合器(分别在组合和分开状态)时终板和融合器自身在前屈、后伸、侧弯和旋转等不同运动状态下的应力值和融合器传导应力在腰4终板的应力分布图,并比较不同条件下应力值的分布情况。2、新型组合式腰椎间融合器的体外生物学评价选用新鲜小牛腰椎制成单独的脊柱功能节段,从前部进行部分纤维环和髓核切除,分别植入新型融合器(在组合和分开状态),按照实验目的的不同进行分组。首先进行组合式椎间融合器的压缩载荷性能测试,接下来测试组合式椎间融合器在装载植骨和未装载植骨的拔出力学性能;最后通过测试在垂直压缩载荷和扭力作用下的活动角度确定组合式腰椎间融合器的稳定性。3、新型组合式腰椎间融合器的动物体内融合实验选取羊做为融合模型的实验动物,分成4组:空白组,摘除椎间盘;自体骨组,植入自体三面皮质髂骨;融合器A组,植入填塞自体骨的单枚组合cage;融合器B组,植入填塞自体骨的分开的椎间撑开器,进行体内融合实验,存活实验动物分别在术后4、8、12周三个时间点麻醉状态下拍X线片,观察植骨融合情况,在术前以及术后1、2、3月进行腰椎融合模型侧位X线片,即椎间隙高度评估,观察融合前后椎间隙高度的变化。4、新型融合器植入对关节突切除腰椎节段稳定性影响的生物力学测试选用新鲜小牛腰椎制成所需标本,按以下序列进行生物力学测试:A组:完整腰椎功能节段→B组:单侧小关节突切除+椎间盘摘除→C组:单侧小关节突切除+椎间盘摘除+同侧新型cage分开植入→D组:单侧小关节突切除+椎间盘摘除+同侧新型cage组合植入→E组:单侧小关节突切除+椎间盘摘除+新型cage分开植入+同侧椎弓根螺钉固定→F组:单侧小关节突切除+椎间盘摘除+新型cage组合植入+同侧椎弓根螺钉固定→G组:单侧小关节突切除+椎间盘摘除+新型cage分开植入+双侧椎弓根螺钉固定。对每个测试序列均持续施加500N的轴向压力下,扭转力矩15牛米,轴向加载速度l.5mm/min。测定并记录FSU节段在轴向压缩、前屈、后伸、左右侧弯下的轴向刚度,左右扭转刚度的测试向关节突切除的同侧和对侧进行。结果1.新型组合式腰椎间融合器成功设计并制造出产品;2.成功建立脊柱三维立体有限元模型,分别包括椎间盘摘除FEM,新型融合器分开和组合时创建的FEM,并获得垂直压力和扭力下轴向压缩、前屈、后伸、侧屈和旋转状态下终板应力强度、轮廓图,和植入新型融合器后其自身的应力值。当新型融合器植入椎间盘摘除的FEM,新型融合器组合时轮廓图显示最大的接触在中心部位,导致在各个加载方向时应力均集中在终板为中心的位置,当融合器分开植入时,轮廓图出现一个面积大的、更宽阔、更分散的终板应力分布区域,在腰4上终板上两侧的对称位置。在压缩、前屈、侧屈和旋转中,分开的融合器比组合时给终板带来更大的应力。最大应力出现在分开的融合器在旋转状态下,但分开的融合器在中心区域的应力值明显小于组合时。3.在对ALIFC进行的压缩载荷性能测试和拔出力测试中,显示ALIFC具有和传统PEEK材料融合器一样的自身载荷承受力和抗拔出能力,在装载植骨时比未装载植骨时有更好的抗压和抗拔出能力,但结果无显著性差异(P>0.05)。在ALIFC稳定性测试中,无论是植骨、传统cage、分开组、ALIFC分开和组合均使腰椎节段稳定性提高,与不稳组相比,有显著统计学差异(P<0.05);ALIFC分开时左、右侧旋转状态下与正常组和植骨组相比,无显著性差异(P>0.05),但与传统融合组、新型组合组相比,ROM数值增大,有统计学差别,说明组合式融合器分开状态在旋转稳定上比传统融合组、新型组合组组合状态差。4.在新型组合式腰椎间融合器的动物体内融合实验中,术前各组动物影像学参数无显著性差异。平均椎间隙高度的检测试结果显示,术后1、2、3月新型cage的组合组与分开组大于自体骨植入组和空白组,术后1、2、3月新型cage组合组与分开组组间差异无显著性差异(P>0.05)。骨融合结果显示,新型cage在组合和分开时,与自体骨植入组相比,融合效果一致,与空白对照组相比,有显著性差异(P<0.05),两组间无显著性差异(P>0.05)。5.在新型融合器植入对关节突切除腰椎节段稳定性影响的生物力学测试中,轴向刚度比较显示,在关节突切除+椎间盘摘除后,腰椎节段明显失稳,在进行新型融合器组合或分开植入后,腰椎刚度,左、右轴向旋转刚度明显改善,出现显著性差异,但低于完整腰椎节段刚度,有显著性差异(P<0.05)。当ALIFC组合或分开植入附加关节突切除侧螺钉内固定后,与单纯融合器植入相比,测试轴向和旋转刚度比完整腰椎节段提高,有显著性差异(P<0.05);组合和分开植入的两者之间的统计学分析,无显著性差异(P>0.05)。实验证明关节突切除+椎间盘摘除后,进行椎间融合器植入附加螺钉内固定,可以恢复腰椎节段的稳定性。结论1.设计制造的组合式多用腰椎间融合器设计合理,具有和腰椎间结构匹配的外形、内部构造和表面处理工艺,PEEK材料强度和弹性模量和与新融合器相适应。2.新型ALIFC分开植入椎间后,有好的应力分布特征,承受植入初期的载荷,防止融合器的下沉;ALIFC自身具有足够的抗载荷能力、拔出力和扭转力学性能,在动物体内椎间融合应用能够维持腰椎间隙高度及融合节段的曲度,在观测时间内实现融合,达到同材质同样外形结构的椎间融合器的融合水平;应用在腰椎不稳模型中,能够使腰椎节段轴向刚度和旋转刚度增加,对腰椎的即刻稳定性作用充分,在抗变形和抗扭转变形方面有一定的优越性。3.组合式多用腰椎间融合器体外实验获得良好结果,可以进行下一步实验。更多还原

【Abstract】 Background and ObjectiveInterbody cages have been certified to restore disc height and to increase stability of the spinal segment, and thereby enhance fusion in the surgical treatment of low back pain、spondylolisthesis and degenerative lumber disease.Concomitantly, the use of these cage devices for lumbar interbody fusion has rapidly gained popularity, cage design and choice of cage material also play a crucial role in long-term results. Techniques of interbody fusion include approaching from anterior, posterior, lateral, posterolateral and transformainal.Traditional open surgery has been evolving toward more minimally invasive techniques in efforts to reduce approach-related morbidity, improve cosmesis, and speed recovery and return to normal activity. Approaches to lumbar discectomy and interbody fusion have been greatly influenced by recent advances in minimally invasive spine surgery, and most techniques have been completed through the use of tubular exposures and endoscopic visualization. It is necessary that new types of cage devices be designed for suitable tubular exposures and endoscopic visualization. As we know, general cages have more large volume comparison with various systerms of narrow tubes and endoscope, sometimes working coaxially through tubular portals limits anatomical access and instrument manipulation, and reliance on two-dimensional images for visualization can be challenging. These limitations may result in compromising objectives for the minimally invasive benefits. A novel, assemble cage , which has relative little volume when on condition of separative ,may be easily access to the interbody via a tubular and endoscopic route; meanwhile it can be used in open surgery for interbody fusion depending on practical requirement when combinational state.Differences in cage design/materical and cage/surgical technique may also significantly affect the biomechanics behavior, fusion effect and even stability of the fused spine segment. The purpose of this study was to design and manufacture a type of ALIFC,and verificate its biomechanics behavior, stability of calf lumbar segment in vitro, fusion effect in goat models and contribution to recovery stability of lumbar isthmic spondylolysis. So experiment study consisted of five parts. First, new type of assemble cage was designed and manufactured for double purposes based on the requirement of MILIF.Secondly, to certificate ALIFC biomechanics behavior by mean of created two FEMs, FEMs were conducted in all directions including axial compression, flexion, extension, lateral bending, and rotation. The evaluation results will focus on endplate stress distribution, peak stress of von Mises, stress of cage.Thirdly, to evaluation its biomechanical behavior through calf specimens study in vitro. Calf lumbar specimens were randomly divided and tested for range of motion (ROM) under the condition of flexion/extension,bending laterally and axial rotation(left/right),axial compressing load and pull-out strength. Forthly, to evaluation cage fusion effect in establishing goat models of lumber interbody fusion. ALIFC were implanted into intervertable space in healthy adult goat moedls,these goat were nured,observed and evaluated for fusion effect through X-ray observation in postoperational time until finish of experiment.Fifthly,to evaluate ALIFC function in treating lumbar instability of calf specimen in vitro, instabile lumbar specimen in calf with single isthmus cleavage were made and put them into biomechanicis test after implanted three types of cages with pedicle screw fixation.Methods①To design the new type of versatile assemble interbody fusion cage and it was manufactured by professional medical instrument company.②3D finite element models were developed, reproducing the human L3-L4 spinal unit in intact condition and after implantation of two different cage models. The instrumented models reproduced the post-operative conditions resulting after implant of the different cages including assemble or separate ALIFC. Simulations were run imposing various loading conditions including axial compression, flexion, extension, lateral bending, and rotation under a constant compressive preload. The evaluation results derived from FEMs data will focus on endplate stress distribution, peak stress of von Mises, stress of cage . Stress distributions on the bony surface were evaluated and discussed.③To evaluation ALIFC biomechanical behavior in vitro by mean of FSU of calf ,twenty-four calf lumbar specimens were randomly divided into 6 groups with 4 specimens in each group including control group,destabilized group,autogenous graft group,traditional PEEK cage group,ALIFCage-1 group,ALIFCage-2 group.All groups were tested for range of motion (ROM) under the condition of flexion,extension,bending laterally and axial rotation(left/right),axial compressing load and pull-out strength using a spinal three dimension analysis system.The strenghth, stiffness of of ALIFC, the different mechanical behaviour influence on FSU motion of calf lumbar when its situation of separate or combined were biomechanically tested and compared to each other by mean of tested data in all direction.④The ALIFC was implanted into intervertebral disc of goat models to find out its influence on spine bone fusion at different phases by X-ray compared with normal interbody fusion cage. Sixteen healthy adult goat were used in this experiment, these ALIFC were implanted into intervertable space,then these goat were nured,observed and evaluated for fusion effect in postoperational time until finish of experiment. During the animal application, fusion rate of ALIFC and fusion process with time change were observated by X-ray exposure and compared with normal bone graft group .⑤To evaluate ALIFC function in treating lumbar instability of calf specimen in vitro, instabile lumbar specimen with single isthmus cleavage were made and put them into biomechanicis test after implanted two types of cages or simultaneously with pedicle screw fixation. The procedure is as follows : A normal FSU→B FSU of single isthmus cleavage→C FSU of single isthmus cleavage with ALIFC implantation (in separate state)→D FSU of single isthmus cleavage with ALIFC implantation (in assemble state)→E FSU of single isthmus cleavage with left pedicle screw fixation with ALIFC implantation (in separate state)→F FSU of single isthmus cleavage with left pedicle screw fixation with ALIFC implantation (in assemble state)→G FSU of single isthmus cleavage with bilateralis pedicle screw fixation with ALIFC implantation (in separate state).Corresponding changes of left/right axial torsion moment and angular displacement,lumbar intervertebral segmental stiffness under various conditions were measured by dynamic multidimensional biomechanical fatigue testing machine and homogeneity of variance test setting the level of statistical significance to 0.05.Result:①Based on the requirement of MILIF,new type of assemble cage was designed and manufactured for double purposes of either MILIF or open interbody fusion surgery. The ALIFC was rectangle shape and made of pure PEEK material according to the practical need of MILIF.It is convenient that new cage be easily fabricated in preoperative preparation and instrument manipulation of inserting fusion segment space through tubular and endoscopic system in operation period.②The FEM analyses approximated the loading situation existing in the initial period after implantation the cage. Following cage insertion, high strains and stresses were concentrated in the contact areas between the cage and endplate. Contact stresses around the implants intend to be concentrated around the periphery of the device. After implantation of ALIFC, The stiffness of new cage in assemble condition was similar to the traditional cage on biomechanical data in FEM. The stresses were symmetrical distribution in lateral areas of the endplate when a separate cage was used in the place of a combination cage, but comparison with the separate cage, the stresses in the endplate decreased significantly at center places where the cage wasnot contacting the endplate .The stress of cage was high in rotation moment, the maximum stress was found in assemble model. The largest difference of stress was found in rotation. In extension, difference of stress was least because almost no stress of cage was measured in both models , and most stress was distributed at the posterior part of the cage. A comparison of peak von Mises stresses on the endplates for a 500-N compression and a 15N·m torsional moment in various loading conditions for spines in the new cage. The stresses were symmetrically distributed in lateral areas of the endplate when a separate cage was used in place of a assemble cage. A maximum stress of 43×107 MPa was seen on the endplate in bending with the separate model, as compared with 25×107 MPa in assemble model .③The maximal compressive load and pull-out force of the ALIFC was 9038N and 726N respective and was in coincident with the maximal demand of safety in human spine. ROM:Statistically significant difference was observed between ALIFCage-1 group and intact group,destabilized group,AG group,under the condition of flexion/extension,bending laterally,but no statistically significant difference compared with T-PEEKCage group and ALIFCage-2 group;Under the condition of axial rotation there was no significant difference between ALIFCage-1 group and intact group,AG group but statistically significant difference was existed compared with T-PEEKCage group,ALIFCage-2 group.Axial compressing load and pull-out strength:The axial compressing load and maximum pull out strength of ALIFCage-1 group were increased and decread compared with T-PEEKCage group, ALIFCage-2 group respectively, which was no statistically significant difference.④During the animal application, all goat models were living and checked by X-ray observation. In fusion test study, ALIFC has high fusion rate alike autogenous bone graft , it can anastate and retain the lumbar physiological antecurvatur, the middle and posterior of the intervetebral disc height, supply enough intension and time for the whole progress of bone graft fusion, prevent the subsidence and migration of the cage.⑤The resection of posterior zygapophysial joint lead to a mechanical instabilityof axial compression, flexion, extension, left/right bending, left/right axial torsion. zygapophysial joint had an important sense on torsional stability,especially on the opposite side.Using ALIFC to treat lumbar instability of calf specimen of single isthmus cleavage had good simulation outcome, it can get all directions stabilization combind with pedicle screw.ConclusionALIFC have enough biomechanical stress and strength on assemble or separate condition ,it can provide enough primary stability for lumbar intervertebral fusion and new cage is a suitable device for load-bearing implants. This type of ALIFC has perspective use to human in the future.更多还原