碳纳米管/羟基磷灰石/聚乳酸可降解椎间融合器实验研究
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摘要
研究背景
椎间融合器(cage)问世以来,脊柱融合便进入新的时代。随着研究深入,椎间融合器无论在材料组成还是形态结构均处于不断改进和完善之中。目前椎间融合器多种多样,根据椎间融合器的外形可分为:圆柱状或圆锥状椎间融合器;长方体或盒形椎间融合器;根据制作材料不同又可分为两类:不可吸收椎间融合器和可吸收椎间融合器。尽管椎间融合器式样不一,制作材料不同,但目的却一致:恢复椎间高度和脊柱的解剖序列,保持脊柱的稳定性。
早期有关椎间融合器临床疗效的报道的确令人鼓舞,但随着椎间融合器的普遍应用、长期的随访观察,与椎间融合器相关的并发症也日益增多。一部分并发症源于椎间融合器材料和设计缺陷,其中又以螺旋型金属椎间融合器的并发症最多。多项实验研究证实:金属材料高弹性模量、螺旋型设计是导致金属螺旋型椎间融合器产生并发症的主要原因:不锈钢的弹性模量为220GPa,钛合金椎间融合器的弹性模量约为110GPa,人体皮质骨的弹性模量为2.4GPa,松质骨的弹性模量仅2.1 Gpa。金属椎间融合器和椎体骨较大的弹性模量差异将产生应力遮挡,融合器中的植骨颗粒缺少应力刺激,导致成骨缓慢,甚至假关节形成。同时应力遮挡还可导致相邻椎体骨质疏松、融合器下沉,椎间高度丢失,严重者发生椎间融合器移位、脱出。金属椎间融合器另一个重要的缺点是不透X线,在照片检时融合器的显影掩盖骨痂的X线表现,导致融合“假象”;同时金属异物在CT或MRI检查中产生伪影,对骨愈合的正确评估产生干扰。
碳纤维维椎间融合器克服了金属椎间融合器上述缺点,但最近研究结果证实:椎间融合后期碳纤维cage与椎体间的摩擦碎屑可引起无菌炎症,不利于椎间融合,时间较长还可导致周围骨质疏松和融合器下沉。最近人们在碳纤维椎间融合器的基础上研制出聚醚醚酮(PEEK)椎间融合器,这种椎间融合器的弹性模量为3.57GPa,比碳纤维椎间融合器更接近人体椎骨弹性模量,大量临床观察结果证实PEEKcage不但能促进椎间融合,同时椎间融合率较较金属高,但作为一种高分子塑料,PEEK在人体内不可吸收,远期并发症也有待进一步观察。
用聚乳酸制作的可吸收椎间融合器不但克服了金属椎间融合器的缺点,又具有PEEKcage低弹性模量的优点,同时聚乳酸在人体内经1.5～2年可彻底分解吸收,不留异物。但是可吸收材料,亦有自己的不足:①力学强度欠佳,不如金属椎间融合器、PEEKcage和碳纤维cage。②聚乳酸在体内降解速度过快,在椎间融合之前其力学强度往往不能满足胸腰椎脊柱载荷要求,PDLLAcage在脊柱轴向载荷作用下发生塌陷、椎间高度丢失、脊柱不稳等现象;③组织相容性不佳,聚乳酸在体内过快降解除了导致cage力学强度降低外,乳酸的堆积还可导致无菌性炎症、溶骨反应。由于上述原因聚乳酸cage尚未推广使用。针对聚乳酸以上缺点本实验研究试图从两个方面提高可降解椎间融合器的力学强度和组织相容性:①向聚乳酸基质中加入增强剂—碳纳米管提高复合材料的初始强度:②添加缓冲剂—羟基磷灰石(HA)控制聚乳酸在体内的降解速度,一方面避免可降解椎间融合器力学强度过快衰减:另一方面弱碱性HA可中和聚乳酸的代谢产物—乳酸,改善复合材料的组织相容性,避免无菌性炎症反应和溶骨反应。
目的
1.研制以碳纳米管(CNTs)、羟基磷灰石(HA)、聚乳酸(PDLLA)为原料的椎间融合器。
2.观察CNTs/HA/PDLLA cage的生物力学特性。
3.体外观察复合材料的细胞毒性和组织相容性。
4.体内观察CNTs/HA/PDLLA cage的生物学性能。
研究方法
1.参考国内外同行业近几年的相关文献报道,设计可吸收椎间融合器的形状和大小,确定CNTs、HA、PDLLA的比例,把上述三种材料按照5:15:80质量比进行球磨混合,经注塑成型研制出CNTs/HA/PDLLA cage,测量其装载植骨量和植骨—终板接触面积,并与等体积的碳纤维cage比较。
2.按照国家ISO10993-1标准,对CNTs/HA/PDLLA的细胞毒性和组织相容性进行评估。选用小鼠L929细胞进行体外急性细胞毒性试验,分为阴性对照组,PDLLA组、CNTs/HA/PDLLA组和阳性对照组,用MTT法测量2、4、7天L929细胞OD值,计算相对增长率,并在倒置显微镜下观察细胞形态。在SD大鼠脊柱两侧种植PDLLA、和CNTs/HA/PDLLA试样,于1、4、12周取材,观察试样周围组织的炎症反应和纤维囊壁情况。
3.将10枚CNTs/HA/PDLLA cage和10枚PDLLA cage置于微机控制电子万能实验机进行压缩试验,测量两种椎间融合器最大抗压缩力,为初始强度,根据压力、两种cage横切面积和位移计算出弹性模量,与高分子PEEK cage进行比较。。将其碎片置于电子显微镜下观察显微结构。
4.选用8具新鲜小牛脊柱标本(L3、4),测量在正常状态的三维运动范围,摘除L3、4髓核,测量失稳状态下的运动范围,然后依次把自体髂骨块、碳纤维cage和CNT s/HA/PLLA cage植入L3、4椎间隙,依次测量上述各组三维运动范围、以及自体髂骨块,碳纤维cage和CNT s/HA/PDLLA cage的最大拔出力。
5.选用18只山羊,随机分成Ⅰ组、Ⅱ组、Ⅲ组,摘除山羊L3-4的髓核,分别植入自体髂骨、PDLLA cage CNTs/HA/PDLLA cage于手术即刻、术后4周、术后12周、术后24周照片,测量椎间高度,比较各组椎间高度变化情况;观察各组椎间融合情况。
结果
1.CNTS/HA/PDLLA cage的植骨容量为1.3cm~3,与终板的接触面积为1.18cm~2,而等体积的碳纤维cage植骨容量为1.2cm~3,与终板的接触面积为1.09cm~2。
2.CNTs/HA/PDLLA组细胞RGR均大于90%,细胞毒性Ⅰ级,种植实验1周,CNTs/HA/PDLLA、PDLLA周围均可见中性粒细胞,炎症反应Ⅳ级,未形成完整囊壁。4周,炎症反应Ⅰ级,囊壁反应Ⅳ级,12周,炎症反应、囊壁反应均Ⅰ级。
3.CNTs/HA/PDLLA cage初始最大抗压缩力为7.453±0.555KN,弹性模量为3.470±0.341GPa;PDLLA cage初始最大抗压缩力为6.004±0.368KN,弹性模量为3.24±0.286 GPa,两者初始最大抗压缩力比较差异显著(P＜0.001);弹性模量比较差异不显著(P＞0.05),说明CNTs/HA/PDLLA cage的最大初始抗压缩力较PDLLA cage明显提高,碳纳米管、羟基磷灰石对复合材料的弹性模量影响不大。CNTs/HA/PDLLA cage与PEEK cage比较:后者最大抗压缩力为8.359KN;弹性模量为3.570GPa,前者最大抗压缩力较后者小,但能满足胸腰椎生物力学要求(青壮年胸腰椎极限载荷为7KN,屈服载荷为3.5 KN),CNTs/HA/PDLLAcage弹性模量较PEEK cage小。
4.CNTs/HA/PDLLA cage和碳纤维cage植入失稳脊柱后,在前屈、后伸、左、右侧屈、左、右轴向旋转六个方向的运动范围较正常组减小,两组比较,差异显著(P＜0.001);与碳纤维cage组比较,差异不显著(P＞0.05),说明CNTs/HA/PDLLA cage植入失稳脊柱组后能恢复脊柱的即刻稳定性,其功效与碳纤维cage相当。髂骨块、CNTs/HA/PDLLA cage、和碳纤维cage最大拔出力分别为152.750±22.253KN、295.575±30.125KN、304.038±32.244KN,碳纤维cage最大拔力与CNTs/HA/PDLLA cage比较,差异不显著(P＞0.05),CNTs/HA/PDLLA cage最大拔出力与髂骨块的最大拔出力大比较,差异显著(P＜0.05),说明CNTs/HA/PDLLA cage植入椎间隙后比自体髂骨块稳定,与碳纤维cage一样不容易移位、脱出。
5.CNTs/HA/PDLLA cage、PDLLA cage和自体髂骨植入山羊椎间隙后三组椎间隙高度有不同程度丢失,丢失最多的为自体髂骨组,4、12、24周椎间高度丢失分别为-0.878±0.393 mm,-0.483±0.232 mm,-0.067±0.058 mm;其次为PDLLAcage组4、12、24周椎间高度丢失分别为-0.556±0.296 mm,-0.817±0.471 mm,-0.074±0.030 mm,PDLLA cage组椎间高度丢失主要集中在8-12周。CNTs/HA/PDLLA cage组椎间高度丢失最少,4、12、24周椎间高度丢失分别为:-0.441±0.233mm,-0.285±0.151 mm,-0.078±0.067mm。CNTs/HA/PDLLA cage组与PDLLA cage组比较,差异显著(P＜0.05),说明CNTs/HA/PDLLA cage组植入动物体内后能更有效地防止椎间隙高度丢失、保持脊柱稳定、促进骨融合。
结论
1.在相同体积的情况下CNTs/HA/PDLLA cage能提供更大的植骨空间和植骨面积。
2.CNTs/HA/PDLLA cage具有良好的组织相容性,细胞毒性Ⅰ级,符合国家内植物标准。
3.CNTs/HA/PDLLA cage初始力学强度较PDLLA cage明显提高,能满足脊柱生物力学要求,碳纳米管增强作用显著。
4.CNTs/HA/PDLLA cage植入失稳的脊柱节段后能恢复脊柱的立刻稳定性,在椎间隙中不容易产生移位。
5.动物实验说明CNTs/HA/PDLLA cage在体内具有良好的力学强度,能有效地防止椎间隙高度丢失,并加速椎间融合,提高融合率。
Backgrounds
Since the proposed introduction of the stainless steel basket as an adjunet to human spinal arthrodesis,great change occured in inter-vertebral fusion history. Although the effect of cage to treat spinal disoder is very good,but some pitfalls have been founded about cage in long term follow-up.The research on cage have not been stop,so numerous types of cage devices have been designed,specially the use of those cage devices for lumbar intervertebral fusion has been rapidly popularized wordwide Posterior lumbar intervertebral fusion(PLIF) was introduced to clinical practice in the mid-1940s by Jaslow and Cloward.Cage technology has profoundly changed the approach to spinal fusion,great success has been achieved in treatment of spinal disorder and injuries.and then there has been a resurgence of intrest in performing interbody fusion.There are many kinds of cage,According to the shape of cage,it can be divided into cylindrical or conical cages;Box-shaped or rectangular cages.According to the materials of cage,there are two kinds of cages no-absorbable cage such as metal cage,absorbable cage.But their have the same aim to provide mechnical stability for spine and restore disc height.Early reports on interbody cages are mainly positive,but with longer follow-up,the number of complications reported is increasing,Most of these complications are inherent to the fact that the cages are non-degradable,especially when made of metal.First,there is a remarkable mismatch between the mechanical properties of metals and bone.High stiffness decreases graft loading within the cage,a condition calling stress shielding.A metal implant thus slows down the fusion process,eventually resulting in pseudarthrosis,corrosion, wear,and ultimately migration A second disadvantage of metal implants is that they are radiopaque and thus eclipse the fusion zone during radiological evaluations. Bioresorbable cages,on the contrary,their stiffness is comparable to that of bone, they are radiolucent,and they resorbable over time.Bioresorbables,however,have their own drawbacks and pitfalls.First,their strength is usually considerably lower than that of metals or non-degradable polymers,Specially when they were implanted in the body of man or animal,degradation would weaken it's mechanical which is just enough to meet the demand of lumbar.Research demonstrate that the PDLLA can not stand the load of the spine after 4 weeks post-operation,when the spine have not healing and need stability,therefore to enhance their initiate mechanical force and to sloe down the degradation rat of PDLLA become the key role
Objectives
In order to tackle the problem of the PDLLA(poly-DL-lactic Acid) cage lack of enough strength to support the spinal axial compression.This study is try to develop CNTs/HA/PDLLA degradation cage,and put it into experiment to observe its property,such as biomechanical,and its influence on the fusion process and its transformation during degrading period in vivo.
Methods
1.Consulting relative domestic and overseas literatures in recent yeas,then to design the strengthen degradable cage which mad from carbon nano-tube(CNTs)、Hydroxyapatite(HA)、PDLLA(poly-DL-lactic Acid),this three kinds of material formed composite have good interface so that CNTs/HA/PDLLA cage mechanical have been enforced;
2.According to the standard of ISO10993-1,the biocompatibility of CNTs/HA/PDLLA was evaluated both in vitro and in vivo including cytetoxicity test, NCTC L929 cells were selected to incubated with PDLA、CNTs/HA/PDLLA、and DMEM.To explore the biocompatibility of CNTs/HA/PDLLA composite,implant test were performed in SD rat
3.Cages was put on computer-contrlled material machine to measure the initial maxium compression strength of PDLLA and CNTs/HA/PDLLA cage,each groups consist of 10 cage.
4.To evaluate effect of the CNTs/HA/PDLA cage in the unstable lumbar spinal function unit(SFU),eight goat SFU of L3-4 were applied,after discectomy,iliac crest,carbon fiber cage,CNTs/HA/PDLLA cage were inserted respectively,to comprise multidirectional flexibility among normal group unstable group,iliac crest group,carbon fiber cage group and CNTs/HA/PDLLA cage group,after that maxium pull-force of each cage and iliac crest were test.Data of experiment were recorded.
5.To observe thee effect of CNTs/HA/PDLLA cage in vivo,lumbar fusion was underwent on 18 female goat,six of them were implanted with iliac crest,six of them applied with PDLLA cage,and the others were treated with CNTs/HA/PDLLA cage. Disc height vary were recorded at after operation,4,12,24week post-operation by radiological assessment and vertebra fusion were evaluated
results
1.CNTs/HA/PDLLA cage was mad with CNTs HA and PDLLA,the molecular weight of 80 million,by injected model,it can provide 1.3cm~3 space for autograft, the interface of autograft and endplate is 1.18cm~2,all of them larger than carbon fiber cage's.
2.The L929 cells incubated with CNTs/HA/PDLA and PDLA group both grew well. With relative growth rate over 95%.The cytotoxicity of CNTs/HA/PDLLA and PDLA were under gradeⅠaccording to the ISO10993-1 standard.For biocompatibility in vivo with SD rats,ICI of gradeⅣoccurred in the muscular tissues around the CNTs/HA/PDLLA and PDLLA implant 1 week after operation without formation of complete capsule,and at 4 week,ICI was lowered to grade 1 with grade 4 capsular reaction.Till week 12,the ICI and capsular reaction were both first grade.
3.The maxium initial compressure force of CNTs/HA/PDLA cage was 7.453±0.555KN,compare with PDLLA cage which maxium initial compressure force was 6.004±0.368KN,there was statistical difference.It was obviously that CNTs/HA/PDLL A cage owned stronger initial mechanical than PDLLA cage.
4.Wathever CNTs/HA/PDLA cage and carbon fibber cage could significantly decrease the ROM of unstable spine at flexion,extension and lateral bending,when their were inserted into goat lumbar L3-4,which discectomy were underwent,there were no significant difference between CNTs/HA/PDLLA cage and carbon fibber cage(P＞0.05);when compare with iliac crest group,the two kinds of cage could enhance the stability of discectomy spine.The maximum pull-out force of iliac crest group,CNTs/HA/PDLLA cage group and carbon fiber cage group were 152.750±22,253KN,295.575±30.125KN,304.038±32.244KN,there were significant difference when iliac group compare with carbon fiber cage and CNTs/HA/PDLLA cage respectively(P＜0.05),There were no significant difference between CNTs/HA/PDLLA cage and carbon cage(P＞0.05),but showed difference when they compared with iliac groups(P＜0.001).
5.CNTs/HA/PDLLA cage own good mechanical property whatever in vitro or in vivo, it's mechanical decent slowly than PDLLA when it were implanted in body,so CNTs/HA/PDLLA cage could maintain disc height after operation,but PDLLA cage degrade rapidly after their implanted in goat,so it loss their mechanical force quickly, therefore disc height loss more obviously than CNTs/HA/PDLLA group,at 4,12, 24 week the loss disc height of the PDLLA group were -0.556±0.296mm,-0.817±0.471 mm,-0.074±0.030 mm respectively,and CNTs/HA/PDLLA group's loss disc height were -0.441±0.233mm,-0.285±0.151 mm,-0.078±0.067mm at 4,12, 24 week pot-operation.When CNTs/HA/PDLLA group'loss disc height compared with PDLLA group's,there was statistical difference(P＜0.005).But two kinds of cage could facilitate veterbrate fusion.
Conclusions
1.CNTs/HA/PDLLA cage could provid more large space and more large surface for graft than carbon fiber cage under the condition of same volume,benefit for verterbra fusion.
2.CNTs/HA/PDLLA owne good biocompatibility and without cytotoxicity,meet the demand of ISO10993-1,therefore CNTs/HA/PDLLA cage could be implanted in body of people.
3.CNTs/HA/PDLA cage owned more strong initial mechanical than PDLA cage, meet the demand of spinal loading.
4.CNTs/HA/PDLA cage could recovered of stable spinal which become unstable after discectomy.
5.CNTs/HA/PDLA cage had good mechanical in the body of goat until the verterbral fusion,and could prenvent from loss disc height.
To sum up,CNTs/HA/PDLLA cage own good biocompatibility and enough mechanical strength to guarantee operation segment stable until fusion,in the same time it can facilitate veterbrate fusion enhance fusion rate,so CNTs/HA/PDLLA cage is promising.
椎间融合器(cage)问世以来,脊柱融合便进入新的时代。随着研究深入,椎间融合器无论在材料组成还是形态结构均处于不断改进和完善之中。目前椎间融合器多种多样,根据椎间融合器的外形可分为:圆柱状或圆锥状椎间融合器;长方体或盒形椎间融合器;根据制作材料不同又可分为两类:不可吸收椎间融合器和可吸收椎间融合器。尽管椎间融合器式样不一,制作材料不同,但目的却一致:恢复椎间高度和脊柱的解剖序列,保持脊柱的稳定性。
早期有关椎间融合器临床疗效的报道的确令人鼓舞,但随着椎间融合器的普遍应用、长期的随访观察,与椎间融合器相关的并发症也日益增多。一部分并发症源于椎间融合器材料和设计缺陷,其中又以螺旋型金属椎间融合器的并发症最多。多项实验研究证实:金属材料高弹性模量、螺旋型设计是导致金属螺旋型椎间融合器产生并发症的主要原因:不锈钢的弹性模量为220GPa,钛合金椎间融合器的弹性模量约为110GPa,人体皮质骨的弹性模量为2.4GPa,松质骨的弹性模量仅2.1 Gpa。金属椎间融合器和椎体骨较大的弹性模量差异将产生应力遮挡,融合器中的植骨颗粒缺少应力刺激,导致成骨缓慢,甚至假关节形成。同时应力遮挡还可导致相邻椎体骨质疏松、融合器下沉,椎间高度丢失,严重者发生椎间融合器移位、脱出。金属椎间融合器另一个重要的缺点是不透X线,在照片检时融合器的显影掩盖骨痂的X线表现,导致融合“假象”;同时金属异物在CT或MRI检查中产生伪影,对骨愈合的正确评估产生干扰。
碳纤维维椎间融合器克服了金属椎间融合器上述缺点,但最近研究结果证实:椎间融合后期碳纤维cage与椎体间的摩擦碎屑可引起无菌炎症,不利于椎间融合,时间较长还可导致周围骨质疏松和融合器下沉。最近人们在碳纤维椎间融合器的基础上研制出聚醚醚酮(PEEK)椎间融合器,这种椎间融合器的弹性模量为3.57GPa,比碳纤维椎间融合器更接近人体椎骨弹性模量,大量临床观察结果证实PEEKcage不但能促进椎间融合,同时椎间融合率较较金属高,但作为一种高分子塑料,PEEK在人体内不可吸收,远期并发症也有待进一步观察。
用聚乳酸制作的可吸收椎间融合器不但克服了金属椎间融合器的缺点,又具有PEEKcage低弹性模量的优点,同时聚乳酸在人体内经1.5～2年可彻底分解吸收,不留异物。但是可吸收材料,亦有自己的不足:①力学强度欠佳,不如金属椎间融合器、PEEKcage和碳纤维cage。②聚乳酸在体内降解速度过快,在椎间融合之前其力学强度往往不能满足胸腰椎脊柱载荷要求,PDLLAcage在脊柱轴向载荷作用下发生塌陷、椎间高度丢失、脊柱不稳等现象;③组织相容性不佳,聚乳酸在体内过快降解除了导致cage力学强度降低外,乳酸的堆积还可导致无菌性炎症、溶骨反应。由于上述原因聚乳酸cage尚未推广使用。针对聚乳酸以上缺点本实验研究试图从两个方面提高可降解椎间融合器的力学强度和组织相容性:①向聚乳酸基质中加入增强剂—碳纳米管提高复合材料的初始强度:②添加缓冲剂—羟基磷灰石(HA)控制聚乳酸在体内的降解速度,一方面避免可降解椎间融合器力学强度过快衰减:另一方面弱碱性HA可中和聚乳酸的代谢产物—乳酸,改善复合材料的组织相容性,避免无菌性炎症反应和溶骨反应。
目的
1.研制以碳纳米管(CNTs)、羟基磷灰石(HA)、聚乳酸(PDLLA)为原料的椎间融合器。
2.观察CNTs/HA/PDLLA cage的生物力学特性。
3.体外观察复合材料的细胞毒性和组织相容性。
4.体内观察CNTs/HA/PDLLA cage的生物学性能。
研究方法
1.参考国内外同行业近几年的相关文献报道,设计可吸收椎间融合器的形状和大小,确定CNTs、HA、PDLLA的比例,把上述三种材料按照5:15:80质量比进行球磨混合,经注塑成型研制出CNTs/HA/PDLLA cage,测量其装载植骨量和植骨—终板接触面积,并与等体积的碳纤维cage比较。
2.按照国家ISO10993-1标准,对CNTs/HA/PDLLA的细胞毒性和组织相容性进行评估。选用小鼠L929细胞进行体外急性细胞毒性试验,分为阴性对照组,PDLLA组、CNTs/HA/PDLLA组和阳性对照组,用MTT法测量2、4、7天L929细胞OD值,计算相对增长率,并在倒置显微镜下观察细胞形态。在SD大鼠脊柱两侧种植PDLLA、和CNTs/HA/PDLLA试样,于1、4、12周取材,观察试样周围组织的炎症反应和纤维囊壁情况。
3.将10枚CNTs/HA/PDLLA cage和10枚PDLLA cage置于微机控制电子万能实验机进行压缩试验,测量两种椎间融合器最大抗压缩力,为初始强度,根据压力、两种cage横切面积和位移计算出弹性模量,与高分子PEEK cage进行比较。。将其碎片置于电子显微镜下观察显微结构。
4.选用8具新鲜小牛脊柱标本(L3、4),测量在正常状态的三维运动范围,摘除L3、4髓核,测量失稳状态下的运动范围,然后依次把自体髂骨块、碳纤维cage和CNT s/HA/PLLA cage植入L3、4椎间隙,依次测量上述各组三维运动范围、以及自体髂骨块,碳纤维cage和CNT s/HA/PDLLA cage的最大拔出力。
5.选用18只山羊,随机分成Ⅰ组、Ⅱ组、Ⅲ组,摘除山羊L3-4的髓核,分别植入自体髂骨、PDLLA cage CNTs/HA/PDLLA cage于手术即刻、术后4周、术后12周、术后24周照片,测量椎间高度,比较各组椎间高度变化情况;观察各组椎间融合情况。
结果
1.CNTS/HA/PDLLA cage的植骨容量为1.3cm~3,与终板的接触面积为1.18cm~2,而等体积的碳纤维cage植骨容量为1.2cm~3,与终板的接触面积为1.09cm~2。
2.CNTs/HA/PDLLA组细胞RGR均大于90%,细胞毒性Ⅰ级,种植实验1周,CNTs/HA/PDLLA、PDLLA周围均可见中性粒细胞,炎症反应Ⅳ级,未形成完整囊壁。4周,炎症反应Ⅰ级,囊壁反应Ⅳ级,12周,炎症反应、囊壁反应均Ⅰ级。
3.CNTs/HA/PDLLA cage初始最大抗压缩力为7.453±0.555KN,弹性模量为3.470±0.341GPa;PDLLA cage初始最大抗压缩力为6.004±0.368KN,弹性模量为3.24±0.286 GPa,两者初始最大抗压缩力比较差异显著(P＜0.001);弹性模量比较差异不显著(P＞0.05),说明CNTs/HA/PDLLA cage的最大初始抗压缩力较PDLLA cage明显提高,碳纳米管、羟基磷灰石对复合材料的弹性模量影响不大。CNTs/HA/PDLLA cage与PEEK cage比较:后者最大抗压缩力为8.359KN;弹性模量为3.570GPa,前者最大抗压缩力较后者小,但能满足胸腰椎生物力学要求(青壮年胸腰椎极限载荷为7KN,屈服载荷为3.5 KN),CNTs/HA/PDLLAcage弹性模量较PEEK cage小。
4.CNTs/HA/PDLLA cage和碳纤维cage植入失稳脊柱后,在前屈、后伸、左、右侧屈、左、右轴向旋转六个方向的运动范围较正常组减小,两组比较,差异显著(P＜0.001);与碳纤维cage组比较,差异不显著(P＞0.05),说明CNTs/HA/PDLLA cage植入失稳脊柱组后能恢复脊柱的即刻稳定性,其功效与碳纤维cage相当。髂骨块、CNTs/HA/PDLLA cage、和碳纤维cage最大拔出力分别为152.750±22.253KN、295.575±30.125KN、304.038±32.244KN,碳纤维cage最大拔力与CNTs/HA/PDLLA cage比较,差异不显著(P＞0.05),CNTs/HA/PDLLA cage最大拔出力与髂骨块的最大拔出力大比较,差异显著(P＜0.05),说明CNTs/HA/PDLLA cage植入椎间隙后比自体髂骨块稳定,与碳纤维cage一样不容易移位、脱出。
5.CNTs/HA/PDLLA cage、PDLLA cage和自体髂骨植入山羊椎间隙后三组椎间隙高度有不同程度丢失,丢失最多的为自体髂骨组,4、12、24周椎间高度丢失分别为-0.878±0.393 mm,-0.483±0.232 mm,-0.067±0.058 mm;其次为PDLLAcage组4、12、24周椎间高度丢失分别为-0.556±0.296 mm,-0.817±0.471 mm,-0.074±0.030 mm,PDLLA cage组椎间高度丢失主要集中在8-12周。CNTs/HA/PDLLA cage组椎间高度丢失最少,4、12、24周椎间高度丢失分别为:-0.441±0.233mm,-0.285±0.151 mm,-0.078±0.067mm。CNTs/HA/PDLLA cage组与PDLLA cage组比较,差异显著(P＜0.05),说明CNTs/HA/PDLLA cage组植入动物体内后能更有效地防止椎间隙高度丢失、保持脊柱稳定、促进骨融合。
结论
1.在相同体积的情况下CNTs/HA/PDLLA cage能提供更大的植骨空间和植骨面积。
2.CNTs/HA/PDLLA cage具有良好的组织相容性,细胞毒性Ⅰ级,符合国家内植物标准。
3.CNTs/HA/PDLLA cage初始力学强度较PDLLA cage明显提高,能满足脊柱生物力学要求,碳纳米管增强作用显著。
4.CNTs/HA/PDLLA cage植入失稳的脊柱节段后能恢复脊柱的立刻稳定性,在椎间隙中不容易产生移位。
5.动物实验说明CNTs/HA/PDLLA cage在体内具有良好的力学强度,能有效地防止椎间隙高度丢失,并加速椎间融合,提高融合率。
Backgrounds
Since the proposed introduction of the stainless steel basket as an adjunet to human spinal arthrodesis,great change occured in inter-vertebral fusion history. Although the effect of cage to treat spinal disoder is very good,but some pitfalls have been founded about cage in long term follow-up.The research on cage have not been stop,so numerous types of cage devices have been designed,specially the use of those cage devices for lumbar intervertebral fusion has been rapidly popularized wordwide Posterior lumbar intervertebral fusion(PLIF) was introduced to clinical practice in the mid-1940s by Jaslow and Cloward.Cage technology has profoundly changed the approach to spinal fusion,great success has been achieved in treatment of spinal disorder and injuries.and then there has been a resurgence of intrest in performing interbody fusion.There are many kinds of cage,According to the shape of cage,it can be divided into cylindrical or conical cages;Box-shaped or rectangular cages.According to the materials of cage,there are two kinds of cages no-absorbable cage such as metal cage,absorbable cage.But their have the same aim to provide mechnical stability for spine and restore disc height.Early reports on interbody cages are mainly positive,but with longer follow-up,the number of complications reported is increasing,Most of these complications are inherent to the fact that the cages are non-degradable,especially when made of metal.First,there is a remarkable mismatch between the mechanical properties of metals and bone.High stiffness decreases graft loading within the cage,a condition calling stress shielding.A metal implant thus slows down the fusion process,eventually resulting in pseudarthrosis,corrosion, wear,and ultimately migration A second disadvantage of metal implants is that they are radiopaque and thus eclipse the fusion zone during radiological evaluations. Bioresorbable cages,on the contrary,their stiffness is comparable to that of bone, they are radiolucent,and they resorbable over time.Bioresorbables,however,have their own drawbacks and pitfalls.First,their strength is usually considerably lower than that of metals or non-degradable polymers,Specially when they were implanted in the body of man or animal,degradation would weaken it's mechanical which is just enough to meet the demand of lumbar.Research demonstrate that the PDLLA can not stand the load of the spine after 4 weeks post-operation,when the spine have not healing and need stability,therefore to enhance their initiate mechanical force and to sloe down the degradation rat of PDLLA become the key role
Objectives
In order to tackle the problem of the PDLLA(poly-DL-lactic Acid) cage lack of enough strength to support the spinal axial compression.This study is try to develop CNTs/HA/PDLLA degradation cage,and put it into experiment to observe its property,such as biomechanical,and its influence on the fusion process and its transformation during degrading period in vivo.
Methods
1.Consulting relative domestic and overseas literatures in recent yeas,then to design the strengthen degradable cage which mad from carbon nano-tube(CNTs)、Hydroxyapatite(HA)、PDLLA(poly-DL-lactic Acid),this three kinds of material formed composite have good interface so that CNTs/HA/PDLLA cage mechanical have been enforced;
2.According to the standard of ISO10993-1,the biocompatibility of CNTs/HA/PDLLA was evaluated both in vitro and in vivo including cytetoxicity test, NCTC L929 cells were selected to incubated with PDLA、CNTs/HA/PDLLA、and DMEM.To explore the biocompatibility of CNTs/HA/PDLLA composite,implant test were performed in SD rat
3.Cages was put on computer-contrlled material machine to measure the initial maxium compression strength of PDLLA and CNTs/HA/PDLLA cage,each groups consist of 10 cage.
4.To evaluate effect of the CNTs/HA/PDLA cage in the unstable lumbar spinal function unit(SFU),eight goat SFU of L3-4 were applied,after discectomy,iliac crest,carbon fiber cage,CNTs/HA/PDLLA cage were inserted respectively,to comprise multidirectional flexibility among normal group unstable group,iliac crest group,carbon fiber cage group and CNTs/HA/PDLLA cage group,after that maxium pull-force of each cage and iliac crest were test.Data of experiment were recorded.
5.To observe thee effect of CNTs/HA/PDLLA cage in vivo,lumbar fusion was underwent on 18 female goat,six of them were implanted with iliac crest,six of them applied with PDLLA cage,and the others were treated with CNTs/HA/PDLLA cage. Disc height vary were recorded at after operation,4,12,24week post-operation by radiological assessment and vertebra fusion were evaluated
results
1.CNTs/HA/PDLLA cage was mad with CNTs HA and PDLLA,the molecular weight of 80 million,by injected model,it can provide 1.3cm~3 space for autograft, the interface of autograft and endplate is 1.18cm~2,all of them larger than carbon fiber cage's.
2.The L929 cells incubated with CNTs/HA/PDLA and PDLA group both grew well. With relative growth rate over 95%.The cytotoxicity of CNTs/HA/PDLLA and PDLA were under gradeⅠaccording to the ISO10993-1 standard.For biocompatibility in vivo with SD rats,ICI of gradeⅣoccurred in the muscular tissues around the CNTs/HA/PDLLA and PDLLA implant 1 week after operation without formation of complete capsule,and at 4 week,ICI was lowered to grade 1 with grade 4 capsular reaction.Till week 12,the ICI and capsular reaction were both first grade.
3.The maxium initial compressure force of CNTs/HA/PDLA cage was 7.453±0.555KN,compare with PDLLA cage which maxium initial compressure force was 6.004±0.368KN,there was statistical difference.It was obviously that CNTs/HA/PDLL A cage owned stronger initial mechanical than PDLLA cage.
4.Wathever CNTs/HA/PDLA cage and carbon fibber cage could significantly decrease the ROM of unstable spine at flexion,extension and lateral bending,when their were inserted into goat lumbar L3-4,which discectomy were underwent,there were no significant difference between CNTs/HA/PDLLA cage and carbon fibber cage(P＞0.05);when compare with iliac crest group,the two kinds of cage could enhance the stability of discectomy spine.The maximum pull-out force of iliac crest group,CNTs/HA/PDLLA cage group and carbon fiber cage group were 152.750±22,253KN,295.575±30.125KN,304.038±32.244KN,there were significant difference when iliac group compare with carbon fiber cage and CNTs/HA/PDLLA cage respectively(P＜0.05),There were no significant difference between CNTs/HA/PDLLA cage and carbon cage(P＞0.05),but showed difference when they compared with iliac groups(P＜0.001).
5.CNTs/HA/PDLLA cage own good mechanical property whatever in vitro or in vivo, it's mechanical decent slowly than PDLLA when it were implanted in body,so CNTs/HA/PDLLA cage could maintain disc height after operation,but PDLLA cage degrade rapidly after their implanted in goat,so it loss their mechanical force quickly, therefore disc height loss more obviously than CNTs/HA/PDLLA group,at 4,12, 24 week the loss disc height of the PDLLA group were -0.556±0.296mm,-0.817±0.471 mm,-0.074±0.030 mm respectively,and CNTs/HA/PDLLA group's loss disc height were -0.441±0.233mm,-0.285±0.151 mm,-0.078±0.067mm at 4,12, 24 week pot-operation.When CNTs/HA/PDLLA group'loss disc height compared with PDLLA group's,there was statistical difference(P＜0.005).But two kinds of cage could facilitate veterbrate fusion.
Conclusions
1.CNTs/HA/PDLLA cage could provid more large space and more large surface for graft than carbon fiber cage under the condition of same volume,benefit for verterbra fusion.
2.CNTs/HA/PDLLA owne good biocompatibility and without cytotoxicity,meet the demand of ISO10993-1,therefore CNTs/HA/PDLLA cage could be implanted in body of people.
3.CNTs/HA/PDLA cage owned more strong initial mechanical than PDLA cage, meet the demand of spinal loading.
4.CNTs/HA/PDLA cage could recovered of stable spinal which become unstable after discectomy.
5.CNTs/HA/PDLA cage had good mechanical in the body of goat until the verterbral fusion,and could prenvent from loss disc height.
To sum up,CNTs/HA/PDLLA cage own good biocompatibility and enough mechanical strength to guarantee operation segment stable until fusion,in the same time it can facilitate veterbrate fusion enhance fusion rate,so CNTs/HA/PDLLA cage is promising.
引文
[1]Wuisman PI,Smit TH.Bioresorbable polymer:heading for a new generation of spinal cages[J].Eur spine,2006,15:133-48.
[2]Jean Y,Abdallah Madi,Marc A,et al.Evaluation of the 96/4PLDLA polymer resorbable lumbar interbody cage in long term animal model[J].Eur Spine,2006,15:1545-33.
[3]Martijin VD,Smit TH,Maurice F,et al.the use of poly-L-lactic acid in the lumbar interbody cages:design and biomechanical evalution in vitro[J].Eur spine J 2003,12:43-50.
[4]Brantigan JW,Steffee AD A carbon fiber implant to aid interbody lumbar fusion.Two-year clinical results in the first 26 patients[J].Spine,1993,18:2106-07.
[5]J M Brady.Resorption rate,route of elimination and ultrastructure of the implant site of polylactic acid in the abdominal wall of the rat[J].Biomed Mater Res.1973,7:155.
[6]Agrawal CM,McKinney JS,Lanctot D,et al.Effects of fluid flow on the in vitro degradation kinetics of biodegradable scaffolds for tissue engineering.Biomaterials,2000,21:2443-52.
[7] Wang Yulin, Wan Yizao, Li Qunying, et al. Study on in vitro degradation behavior of C/PLA composite [J]. Functional Materials, 2001, 32: 553-5.
[8] Saikku A, Ckstrom B A, Tulamo R M. Material properties of absorbable self-reinforced fibrillated poly-96L/4 D-lactid(SR-PLA96) rods; A study in vitro and in vivo [J]. Journal of Materials Science: Materials in Medicine, 1999, 10(1): 1-8.
[9] Qi Jingang, Cao Liyun, Wang Jianzhong, et al. In vitro degradation characteristic of carbon fiber reinforced Polylactide (C/PLA) composite [J]. Acta Materiae Compositae Sinica, 2005, 22(2): 34-7.
[10] Wan Yizao, Wang Yulin, Li Laifeng, et al. Influence of interfacial condition on vitro degradation behavior of C/PLA composites [J]. Chinese Journal of Materials Research, 2002, 16(3): 268-72.
[11] Oksman K, Skrifvars M, Selin J F, et al. Natural fibers as reinforcement in polylactic acid ( PLA) composites [ J]. Composites Science and Technology, 2003,63(9): 1317-24.
[12]Bezer M, Yildirim Y, Erol B, Guven Absorbable self-reinforced Polylactide (SR-PLLA) rods vs rigid rods (K-wire) in spinal fusion: an experimental study in rabbits[J]. Eur Spine J. 2005,14: 227-33.
[13] Wan Yizao, Wang Yulin, Han Keyu, et al. Development of carbon fiber reinforced polymer composite bone plate for fracture fixation polymer [J]. Materials Science and Engineering, 2001,17(1): 35-8.
[14]Suchanek W, Yoshimura M. Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants [J]. Journal of Materials Research, 1998, 13(1): 94-7.
[15]Heise U, Osborn J F, Duwe F. Hydroxyapatite ceramic as a bone substitute [J]. Int Orthop, 1990,14(3): 329-38.
[16]Claes L, Ignatius A Development of new, biodegradable implants[J]. Chirurg ,2002, 73:990-6.
[17]Gautier SE, Oudega M, Fragoso M, et al. Poly(alpha-hydroxyacids) for application in the spinal cord: resorbability and biocompatibility with adult rat Schwann cells and spinal cord[J]. Biomed Mater Res ,1998, 42:642-54.
[18]Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lac-tide (PLA) I : Basic characteristics [J]. Biomaterials, 1999,20(9): 859-77.
[19]Kin-Tak Lau, David Hui. Effectiveness of using carbon nanotubes as nano-reinforcements for compositestructures[J]. Letters to the editor Carbon,: 1597-617.
[20]Brantigan JW, McAfee PC, Cunningham BW, Wang H, Orbegoso CM (1994) Interbody lumbar fusion using a carbon fiber cage implant versus allograft bone. An investigational study in the Spanish goat[J]. Spine 19:1436-44 .
[21] Webster TJ, Waid MC, McKenzie JL,et al. Nanobiotechnology: carbon nanofibres as improved neural an orthopaedic implants. Nano Tech, 2004; 15: 48.
[22]Kettler A, Wilke HJ. Effects of neck movements on stability and subsidence in cervical interbody fusion: an in vitro study. [J] Neurosurg, 2001,94(supply): 197-207.
[23]Kanayama M, Cunningham BW, Haggerty CJ, et al. In vitro biomechanical investigation of the stability and stxess-shielding effect of lumbar interbody fusion devices[J]. J Neurosurgery 2000; 93 (Suppl 2): 259-65.
[24]Ilke HJ, Kettler A, Goetz C, et al, Subsidence resulting from simulated postoperative neck movements: an in vitro investigation with a new cervical fusion Cage[J]. Spine, 2000,25(21): 276-280.
[1]Bhattacharyya AR,Sreekumar TV,Liu T,et al.Crystallization and orientation studies in polypropylene/single wall carbon nano-tube composite[J].Polymer,2003.44:2373-7.
[2]GB/T16886.6-1997·医疗器械生物学评价[S].第六部分:植入后局部反应试验:5-6.
[3]Kawaguchi M,Fukushima T,Hayakawa T,et,al.Preparation of carbon nanotube-alginate nanocomposite gel for tissue engineering.[J].Dent Mater J.2006 Dec;25(4):719-25.
[4]Zhang LW,Zeng L,Barron AR,et,al.Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes..[J].Int J Toxicol.2007 Mar-Apr;26(2):103.
[5]Montereio-Riviere NA,Inman AO,Wang YY,et,al.surfactant effect on carbon nanotube interactions with human keratinocytes[J].Nanomedieine,2005 Dec;1(4):293-9
[6]Monteiro-Riviere NA,NA,Inman AO,Wang YY.et al..Surfactant effects on carbon nanotube interactions with human keratinocytes[J],Nanomedicine.2005Dec;1(4):293-9.
[7]Wick P,Manser P,Limbach L K,et al.The degree and kind of agglomeration affect carbon nanotube cytotoxicity[J],Toxicol Lett.2007 Jan 30;168(2):121-31.
[8]Sato Y,Yokoyama A,Shibata k,et al.Influence of length on cytotoxicity of multi-walled carbon nanotubes against human acute monocytic leukemia cell line THP-1 in vitro and subcutaneous tissue of rats in vivo.[J].Mol Biosyst.2005Jul;1(2):176-82.
[9]Magrez A,Kassas S,Salicio V,et al.Cellular toxicity of carbon-based nanomaterials[J].Nano Lett.2006 Jun;6(6):1121-5.
[10]Wester TJ,Waid MC,Mckenize JI,et al.Nano-biotechnology:carbon nanofibers as improved neural and orthopaedic implants.Nano Tech,2004;15:48.
[11]Hu H,Ni YC,Montana V,et al.Chemically functionalized carbon nanotubes as substrates for neuronal growth.Nano Lett.2004;(3):507.]
[12]刘金标,陈建庭.珍珠层/聚乳酸重组人工骨的研制及其相关性能检测.[J].第一军医大学学报,2002,22(3):236-8.
[13]吴一民,陈建庭,孙伟,等.珍珠层聚乳酸人工骨的细胞毒性实验.[J].中国临床康复,2002,12(6):1737-9.
[14]动物细胞培养技术[M].广州:华南理工大学出版社,200:131-2.
[15]国家技术监督局.中华人民共和国国家标准:医用有机硅材料生物学评价试验方法(GB/T16175-1996)[S].北京:中国标准出版社,1996:6,17-8。
[16]赵冬梅,刘中浩,武士清,等.碳纳米管/羟基磷灰石复合材料兔胫骨生物相容性研究[J].中国生物医学工程学报.2006;25(3):342-5.
[1]M.Krammer,R.Dietl,C.B.Lumenta,et al.Resistance of the Lumbar Spine Against Axial Compression Forces after Implantation of Three Different Posterior Lumbar Interbody Cages[J].Acta Neurochir2001,143:1217-22.
[2]Stephen J.Ferguson,Judith M.A.Visser,Anne Polikeit.The long-term mechanical integrityof non-reinforced PEEK-OPTIMA polymer for demanding spinal applications:experimental and finite-element analysis[J].Eur Spine J(2006) 15:149-56。
[3]Rokkanen P,Bostman O,Vainionpaa S,et al.Absorbable devices in the fixation of fracture[J].J Trauma,1996,40(3 suppl):S123-7.
[4]Tomala p,Vasenius J,Vainionpaa S,et al.Ultra-high-strength asorbable self-reinforled polyglycolide(SR-PGA) composite rods for internal fixation of bone fractures[J].J BiomedMater Res,1991,25(1)1-22.
[5]Pohjonen T,Helevirta P,et al.Strength retention of self-reinforced poly-L-lactide screws[J].Mater Med,1997,8:311-20.
[6]Matsusue Y,Nakamura T,Iizuka H,Shimizu K.A longterm clinical study on drawn poly-L-lactide implants in orthopaedic surgery[J].JLong-Term Effects Medical Implants,1997,7:119-37.
[7]Bergsma JE,Bruijin de WC,Rozema FR,Bos RRM,Boering G.Late degradation tissue response to poly(L-lactide) bone plates and screws[J].Biomaterials,1995,16:25-31.
[8]薄颖慧.聚乳酸/羟基磷灰石复合材料的研究[J].中山大学学报(自然科学版),1999,3(38)43.
[9]Clase LE.Mechanical characterrization of biodegradable implants.Clinical materials,1991:10:41-6.
[10].Athansiou KA.Agrawal CM,Barber FA,et al.Orthopaedic applications for PLA-PGA biodegradable polymers.Arthroscopy,1998,14(7):726-37.
[11] Mainil-varlet P. Rahn B, Gogolewski. Long-term in vivo degradation and bone reaction to various polylactides[J]. Biomaterials 1997,(18):257-66.
[12] Tormala P. biodegradable self-rein-forced. Compositematerials , manufactturing structure and mechanical properties[J]. Clinical Materials, 1992,10:29-33.
[13] Rokkanen P, Bostman 0, Vainionpaa S. biodegradable implants in fracture fixation:earl results of treatment of fracture of the ankle. Lancet, 1985,1:1422-30.
[14] Bostman 0. biodegradable internal fixation for malleolar fractures:a prospective randomized trial. JBJS(Br), 1987, 6:1015.
[15].Hollingger JO. Preliminary report on the osteogenic potentional of biodegradable copolymer of Polylactide and polyglycolide., J Biomed Mater Res, 1983, 17:71.
[16] Bostmam P. Foreign-body reactions to polyglycolic screws. Acta orthop scand, 1992.63(2): 173-6.
[17] Heng BC, Cao T, Stanton LW.et al. Strategies for directing the differentiation of stem cells into the osteogentic lingeage in vitro[J].J Bone Miner Res,2004, 19(9)1379-94.
[18] Frank K.Robert P. Matti S. Bioabsorbable interbody cages in a sheep cervical spine fusion model [J]. Spine, 2004, 29(17): 1845-55.
[19] Mike T. Masaka K. Lmai Y. et al. Experience with freeze-dried PGLA/HA2/rhBMP-2 as a bone graft substitute Craniomaxillofac Surg, 2000, 28( 5):294-8.
[20] Frank K,Robert P,Matti S. Bioabsorbable interbody cages in a sheep cervical spine fusion model[J].Spine,2004,29(17):1845-55.
[21] Tormala p, Vasenius J, Vainionpaa S; et al. Utra-high-strength absorbabls self-reinforced polyglycolide (SR-PGA) composite rods for interal fixation of bone fracture in vitro and in vivo study[J]. Biomed Mater Res, 2005, 25(1): 1-22.
[22] ZHAO Ping. Carbon fiber/carbon nano-tubes strengthened calcium phosphate cement composite and its biocompatibility (in Chinese, dis-sertation). Jinan: Shandong University, 2005.
[23] The use of poly-L-lactic acid in lumbar interbody cages; design and biomechanical evaluation in vitro[J].Eur spine,2003,12(10):34-40.
[1]朱青安,胡庆茂,李慧友,等.脊柱三维运动分析系统及其在腰椎稳定性分析中的应用[J].中国脊柱脊髓杂志,1995,5(4):153-6.
[2]McAfee PC.Interbody fusion cages in reconstructive operations on the spine[J].Bone Joint Surg(Am),1999,81(6):859-80.
[3]Van Dijk M,Smit TH,Sugihara S,et al.The effect of Cage stiffness on the rate of lumbar interbody fusion:an in vivo model using poly(1-lactic Acid) and、titanium Cages[J].Spine.2002;27:682-8.
[4]Ray CD.Threaded titanium cages for lumbar interbody fusions [J].Spine,1997,22(6):667-79.
[5]Steffen T,Tsantrizos A,Fruth I,et al.Cages:designs and concepts[J].Eur Spine J,2000,9(Suppl 1):89-94.
[6]Kandziora F,P flugmacher R,Schafer J,et al.Biomechanical comparisons of cervical spine interbody fusion Cages[J].Spine.2001 Sep 1;26(17):1850-7.
[7]Wilke HJ,Kettler A.Primary stabilizing effect of interbody fusion devices for the cervical spine:an in vitro comparison between three different Cage types and bone cement[J].Eur Spine,2000,9(5):410-6.
[8]Kohn J,Langer R.Bioresorbable Material[M].New York:Academic Press,1999.64-73.
[9]Thomas KA.Biomechanics and Biomaterials.[M].Phicadel-phia:WB Saunders,2001.43-51.
[10]Bell GH.Variation in stregth of vertebrae with age and their relation to osteoporosis[J].J Calcif Tissue Res,1967,1(1):75-8.
[11]Yu BS.Biomechanical comparison of the posterolateral fusion and posterior lumbar interbody fusion using pedicle screw fixation system for unstable lumbar spine[J].J Hokkaido Med Sci,2003,78(3):211-8.
[12]黄东生,刘尚礼.椎间盘的生物力学[J].医用生物力学杂志,1997,12(3):175-8.
[13]White AA.Clinical Biomechanics of the Spine[M].Philadelphia:Lippincott,1978.180-4.
[14].Farfan HF.Mechanical disorders of the low back.[M].Philadel-phia:Lea &Febiger,1973.33-5.
[1]Wing KJ,Fisher CG,O'Connell JX,Wing PC.Stopping nicotine exposure before surgery.The effect on spinal fusion in a rabbit model[J].Spine,2000 Jan,25(1):30-4.17.
[2]McLain RF,Yerby SA,Moseley TA.Comparative morphometry of L4 vertebrae:comparison of large animal models for the human lumbar spine 1[J].Spine,2002Apr 15,27(8):E200-6.
[3]Steffen T,Marchesi D,Aebi M.Posterolateral and anterior interbody spinal fusion models in the sheep 1[J].Clin Orthop,2000 Feb,(371):28-37.
[4]Smit TH.The quadruped as an in vivo model for the study of the spine biome -chanical considerations 1[J].Eur Spine J 2002,11:137-144.
[5]Oxland TR,Hoffer Z,Dipling TN,et al.A comparative bio -mechanical investi-gation of anterior lumbar interbody cages:central and bilateral approaches 1[J]Bone Joint Surg Am.2000,82:383-393.
[6]Smit TH,Krijnen MR,Dijk MV,et al.Application of polylactides in spinal cages:Studies in a goat model 1[J].Mater sci:Mater Med 2006 Nov 17(11):1237-1244.
[7]Martijn van,Dijk T H.Smit M,et al.The use of poly-L-lactic acid in lumbar inter-body cages:design and biomechanical evalua-tion l[J].Eur Spin J 2003 12:34-40.
[8]Steffen T,Tsantrizos A,Aebi M Effect of implant design and endplate preparation on the compressive strength of interbody fusion constructs 1[J].Spine 2000,25:1077-1084.
[9]金大地,赵亮,瞿东滨,等.腰椎间盘人工髓核置换术后中期疗效分析.[J].中华骨科杂志,2007,27(5):326-330.
[10]金大地,王吉兴,陈建庭,等.腰椎间盘突出症和椎管狭窄症手术并发症的回顾性分析.[J].中华骨科杂志,2003,24(1):653-656.
[11]Smit TH,Krijnen MR,Dijk van,et al.Application of polylactides in spinal cages;Studies in a goad model 1[J].Mater Sci:Mater Med.2006,17:1237-1244.
[1]Thomas Steffen,Anthony Tsantrizos,Irmgard Fruth,et al.Cages:designs and concepts.[J].Eur spine 2000.9(Suppl 1):89-94.
[2]金大地,赵亮,瞿东滨,等.腰椎间盘人工髓核置换术后中期疗效分析.[J].中华骨科杂志,2007,27(5):326-30.
[3]Kuslich SD,Danielson G,Dowdle JD,et al.Four years follow-up results of lumbar spine arthrodesis using the Bagby and Kus-lick lumbar fusion cage.[J].Spine,2000,25;2656-62.
[4]Bagby GW.Arthrodesis by the distraction-compression method using a stainless steel implant[J].Orthopedics,1988,11:931-34.
[5]Shikinami Y,Okuno M(1999) Bioresorbable devices made of forged composites of hydroxyapatite(HA) particles and poly-1-lactide(PLLA):Part Ⅰ:basic characteristics.Biomaterials 20(9):859-77
[6]Shikinami Y,Okuno M(2001) Bioresorbable devices made of forged composites of hydroxyapatite(HA) particles and poly-1-lactide(PLLA):Part Ⅱ:practica properties of miniscrews and miniplates85-97.
[7]Kulkarni RK,Pani KC,Neuman C,et al:Polylactic acid for surgical implants[J].Arch Surg,1966,93:839-43.
[8]Bostman O.Absorbable implants for the fixation of fracture.J Bone,Joint, Surg,1991,73A:148.
[9]Gogolowski S,Resorbable polymers for intermal fixation,Clinical Material 1992,10-13.
[10]Satavirta S.Immune response to polyglycolic acid implant.JBJS,1990,11:10-13.
[11]Christell.Biodegradable.composites for internal fixation[J].biomaterial,1982,7:271-80.
[12]Gogolowski S,Resorbable polymers for intermal fixation,Clinical Material,1992,8:10-13.
[13]Christel.Biodegradable.composites for internal-fixation.biomaterial,1982,11:271-80.
[14]Tormala P,Pohjonen T.Rokkanen P.Bioresorbable polymers:materials technology and surgi-cal application.Proc Inst Mesh Eng H,1998,212(2):101-2.
[15]Bostman OM,Pihlajamkai HK.Adverse tissue reactions bioabsorbable fixation devices[J].Clin Orthop,2000,371:216-27.
[16]Gerlanch[11.Gerlanch.In-vivo and clinical evalua-tions of poly (L-Lactide)plates and crews for use in maxillofacial traumatology.Clinical material,1993,1:21-4..
[17]吴一民,陈建庭,孙伟,等.珍珠层聚乳酸人工骨的细胞毒性实验.[J].中国临床康复,2002,12(6):1737-1739.
[18]Rozema FR,et al.Influence of re-sorbable poly-(L-Lactide) bone plates and screws on the dose distributions of radiotherapy beams.Int J oral,2006,10(3):135-40.
[19]Hollinger JO.Preliminaryreportonthe osteogenic potential of biodegradable copolymer of polylactide(PLA)and polyglycolide(PGA)[J].BiomedMaster Res,1983,17 : 71-82.
[20]Hollinger JO,Brekke J,Cruskin E,et al.Role of bone substitute [J].Clin Orthop, 1996,(324) : 55-6.
[21] Smith R,TorresA,LiSm,et al. Screening of microorganisms for biodegradation of poly (lactic-acid) and lactic acid containing polymers [J].BiomedMater Res, 1987,21(7) : 991-6.
[22]Martjin VD,Theo HS,Elisabeth HB, et al.Bioabsorbable polyL-lactic acid cages for lumbar interbody fusion:three-year follow-up radiographic,histologic,and histomorphometric analysis in goats[J].Spine,2002,27(23):2706-14.
[23] Caleb RL,Michael H,Bret A,et al. Cervical spine fusion with bioabsorble cages [J]. Neurosurg Focus,2004,16(3) :45 -52.
[24]Smit TH, Burger EH,et al. Bioabsorbable poly-L-lactic acid cages for lumbar interbody fusion: three-year follow-up radiographic, histologic, and histomorphometric analysis in goats [J]. Spine, 2002 ,27 (23):2715-20.
[25] Wuisman P I J, Van Dijk M, Tunc D C, et al. In Vitro and in vivo degradation of bioabsorbable PLLA spinal fusion cages [J]. Biome Mater Res,2002(Appl Biomater),63:752-759.
[26]Smit TH, Krijnen MR, Dijk MV, et al. Application of polylactides in spinal cages: studies in a goat model.[J] Mater Sci: Mater Med 2006 17:1237-44.
[27] Jean Y, Lazennec, Abdallah Madi, Mare A, et al. Evaluation of the 96/4PDLLA polyer resorbable lumbar interbody cage in a long term animal model[J].Eur Spine J 2006 ,15:1545-53.
[28]Eind T, Pflugmacher R, Koch C, et al. Spinal fusion with bioresorbable cages -severe degradation effects. Eur Spine[J]. 2005,14(11):20-3.
[29] Kandziora F, Pflugmacher R, Scholz M, et al Bioabsorbable interrbody cages in a sheep cervical spine fusion model.[J]. Spine 2004,29(3): 1845-55.
[30]Vaccaro AR. Robbins, Madigan L.Early findings in a pilot study of anterior cervical fusion in which bioabsorbable interbody space were used [J]. Neurosurg Focus,2004,16(3): E6.
[31]Lanaman TH. Hopkins TJ.Early findings In a pilot study of anterior cervical interbody fusion in which recombinant human bone morphogeneticprotein- 2 was used with poly(L lactide- co-D. L-lactide) bioabsorbable implants [J]. Neurosurg Focus,2004,16(3):E6.
[32]Subach BR. Haid RR.Roldts CE, et al. Posterior lumbar interbody fusion(PLIF) using an impacted,bioabsorbable device. American Association of Neurological Surgeons, Congress of Neurological Surge-ons:joint section on spinal disorders and peripheral nerves[C]. Orlando. FL. 1999, 12: 113-20..
[33]Couture DE, Branch CL. Posterior lumbar interbody fusion with bioabsorbable spacers and local autograft in a series of 27 patients[J]. Neurosurg Focus,2004, 16(3):E8.
[34]Lanman TH. Hopkins TJ.Lumbar interbody fusion after treat- ment with recombinant human bone morphogenetic protein- 2 added to poly ( L- lactide- co- D, L- lactide) bioresorbable im-plants[J] .Neurosurg Focus, 2004, 16(3):E9.
[35]Coe JD. Vaccaro AR.Instrumented transforaminal lumbar interbody fusion with bioresorbable polymer implants and iliac crest autograft[J]. Spine, 2005, 30(Suppl 17):76-83.
[36]Heng BC, Cao T, Stanton LR.et al. Strategies for directing the differentiation of stem cells into the osteogenic lineage in vitro [J]. Bone Miner Res,2004,19(9): 1379-94.
[37] Mike T. Maeaka K. l,mai Y. et al. Experience with freeze-dried PGLA/HA2/rhBMP-2 as a bone graft substitute[J]. Craniomaxillofac Surg,2000,28(5):294-8.
[38]Caleb RL.Michael H.Rret A.et al.Cervical spine fusion with bioabsorble cages[J].Neurosurg Focus,2004,16(3):E4..
[2]Jean Y,Abdallah Madi,Marc A,et al.Evaluation of the 96/4PLDLA polymer resorbable lumbar interbody cage in long term animal model[J].Eur Spine,2006,15:1545-33.
[3]Martijin VD,Smit TH,Maurice F,et al.the use of poly-L-lactic acid in the lumbar interbody cages:design and biomechanical evalution in vitro[J].Eur spine J 2003,12:43-50.
[4]Brantigan JW,Steffee AD A carbon fiber implant to aid interbody lumbar fusion.Two-year clinical results in the first 26 patients[J].Spine,1993,18:2106-07.
[5]J M Brady.Resorption rate,route of elimination and ultrastructure of the implant site of polylactic acid in the abdominal wall of the rat[J].Biomed Mater Res.1973,7:155.
[6]Agrawal CM,McKinney JS,Lanctot D,et al.Effects of fluid flow on the in vitro degradation kinetics of biodegradable scaffolds for tissue engineering.Biomaterials,2000,21:2443-52.
[7] Wang Yulin, Wan Yizao, Li Qunying, et al. Study on in vitro degradation behavior of C/PLA composite [J]. Functional Materials, 2001, 32: 553-5.
[8] Saikku A, Ckstrom B A, Tulamo R M. Material properties of absorbable self-reinforced fibrillated poly-96L/4 D-lactid(SR-PLA96) rods; A study in vitro and in vivo [J]. Journal of Materials Science: Materials in Medicine, 1999, 10(1): 1-8.
[9] Qi Jingang, Cao Liyun, Wang Jianzhong, et al. In vitro degradation characteristic of carbon fiber reinforced Polylactide (C/PLA) composite [J]. Acta Materiae Compositae Sinica, 2005, 22(2): 34-7.
[10] Wan Yizao, Wang Yulin, Li Laifeng, et al. Influence of interfacial condition on vitro degradation behavior of C/PLA composites [J]. Chinese Journal of Materials Research, 2002, 16(3): 268-72.
[11] Oksman K, Skrifvars M, Selin J F, et al. Natural fibers as reinforcement in polylactic acid ( PLA) composites [ J]. Composites Science and Technology, 2003,63(9): 1317-24.
[12]Bezer M, Yildirim Y, Erol B, Guven Absorbable self-reinforced Polylactide (SR-PLLA) rods vs rigid rods (K-wire) in spinal fusion: an experimental study in rabbits[J]. Eur Spine J. 2005,14: 227-33.
[13] Wan Yizao, Wang Yulin, Han Keyu, et al. Development of carbon fiber reinforced polymer composite bone plate for fracture fixation polymer [J]. Materials Science and Engineering, 2001,17(1): 35-8.
[14]Suchanek W, Yoshimura M. Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants [J]. Journal of Materials Research, 1998, 13(1): 94-7.
[15]Heise U, Osborn J F, Duwe F. Hydroxyapatite ceramic as a bone substitute [J]. Int Orthop, 1990,14(3): 329-38.
[16]Claes L, Ignatius A Development of new, biodegradable implants[J]. Chirurg ,2002, 73:990-6.
[17]Gautier SE, Oudega M, Fragoso M, et al. Poly(alpha-hydroxyacids) for application in the spinal cord: resorbability and biocompatibility with adult rat Schwann cells and spinal cord[J]. Biomed Mater Res ,1998, 42:642-54.
[18]Shikinami Y, Okuno M. Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lac-tide (PLA) I : Basic characteristics [J]. Biomaterials, 1999,20(9): 859-77.
[19]Kin-Tak Lau, David Hui. Effectiveness of using carbon nanotubes as nano-reinforcements for compositestructures[J]. Letters to the editor Carbon,: 1597-617.
[20]Brantigan JW, McAfee PC, Cunningham BW, Wang H, Orbegoso CM (1994) Interbody lumbar fusion using a carbon fiber cage implant versus allograft bone. An investigational study in the Spanish goat[J]. Spine 19:1436-44 .
[21] Webster TJ, Waid MC, McKenzie JL,et al. Nanobiotechnology: carbon nanofibres as improved neural an orthopaedic implants. Nano Tech, 2004; 15: 48.
[22]Kettler A, Wilke HJ. Effects of neck movements on stability and subsidence in cervical interbody fusion: an in vitro study. [J] Neurosurg, 2001,94(supply): 197-207.
[23]Kanayama M, Cunningham BW, Haggerty CJ, et al. In vitro biomechanical investigation of the stability and stxess-shielding effect of lumbar interbody fusion devices[J]. J Neurosurgery 2000; 93 (Suppl 2): 259-65.
[24]Ilke HJ, Kettler A, Goetz C, et al, Subsidence resulting from simulated postoperative neck movements: an in vitro investigation with a new cervical fusion Cage[J]. Spine, 2000,25(21): 276-280.
[1]Bhattacharyya AR,Sreekumar TV,Liu T,et al.Crystallization and orientation studies in polypropylene/single wall carbon nano-tube composite[J].Polymer,2003.44:2373-7.
[2]GB/T16886.6-1997·医疗器械生物学评价[S].第六部分:植入后局部反应试验:5-6.
[3]Kawaguchi M,Fukushima T,Hayakawa T,et,al.Preparation of carbon nanotube-alginate nanocomposite gel for tissue engineering.[J].Dent Mater J.2006 Dec;25(4):719-25.
[4]Zhang LW,Zeng L,Barron AR,et,al.Biological interactions of functionalized single-wall carbon nanotubes in human epidermal keratinocytes..[J].Int J Toxicol.2007 Mar-Apr;26(2):103.
[5]Montereio-Riviere NA,Inman AO,Wang YY,et,al.surfactant effect on carbon nanotube interactions with human keratinocytes[J].Nanomedieine,2005 Dec;1(4):293-9
[6]Monteiro-Riviere NA,NA,Inman AO,Wang YY.et al..Surfactant effects on carbon nanotube interactions with human keratinocytes[J],Nanomedicine.2005Dec;1(4):293-9.
[7]Wick P,Manser P,Limbach L K,et al.The degree and kind of agglomeration affect carbon nanotube cytotoxicity[J],Toxicol Lett.2007 Jan 30;168(2):121-31.
[8]Sato Y,Yokoyama A,Shibata k,et al.Influence of length on cytotoxicity of multi-walled carbon nanotubes against human acute monocytic leukemia cell line THP-1 in vitro and subcutaneous tissue of rats in vivo.[J].Mol Biosyst.2005Jul;1(2):176-82.
[9]Magrez A,Kassas S,Salicio V,et al.Cellular toxicity of carbon-based nanomaterials[J].Nano Lett.2006 Jun;6(6):1121-5.
[10]Wester TJ,Waid MC,Mckenize JI,et al.Nano-biotechnology:carbon nanofibers as improved neural and orthopaedic implants.Nano Tech,2004;15:48.
[11]Hu H,Ni YC,Montana V,et al.Chemically functionalized carbon nanotubes as substrates for neuronal growth.Nano Lett.2004;(3):507.]
[12]刘金标,陈建庭.珍珠层/聚乳酸重组人工骨的研制及其相关性能检测.[J].第一军医大学学报,2002,22(3):236-8.
[13]吴一民,陈建庭,孙伟,等.珍珠层聚乳酸人工骨的细胞毒性实验.[J].中国临床康复,2002,12(6):1737-9.
[14]动物细胞培养技术[M].广州:华南理工大学出版社,200:131-2.
[15]国家技术监督局.中华人民共和国国家标准:医用有机硅材料生物学评价试验方法(GB/T16175-1996)[S].北京:中国标准出版社,1996:6,17-8。
[16]赵冬梅,刘中浩,武士清,等.碳纳米管/羟基磷灰石复合材料兔胫骨生物相容性研究[J].中国生物医学工程学报.2006;25(3):342-5.
[1]M.Krammer,R.Dietl,C.B.Lumenta,et al.Resistance of the Lumbar Spine Against Axial Compression Forces after Implantation of Three Different Posterior Lumbar Interbody Cages[J].Acta Neurochir2001,143:1217-22.
[2]Stephen J.Ferguson,Judith M.A.Visser,Anne Polikeit.The long-term mechanical integrityof non-reinforced PEEK-OPTIMA polymer for demanding spinal applications:experimental and finite-element analysis[J].Eur Spine J(2006) 15:149-56。
[3]Rokkanen P,Bostman O,Vainionpaa S,et al.Absorbable devices in the fixation of fracture[J].J Trauma,1996,40(3 suppl):S123-7.
[4]Tomala p,Vasenius J,Vainionpaa S,et al.Ultra-high-strength asorbable self-reinforled polyglycolide(SR-PGA) composite rods for internal fixation of bone fractures[J].J BiomedMater Res,1991,25(1)1-22.
[5]Pohjonen T,Helevirta P,et al.Strength retention of self-reinforced poly-L-lactide screws[J].Mater Med,1997,8:311-20.
[6]Matsusue Y,Nakamura T,Iizuka H,Shimizu K.A longterm clinical study on drawn poly-L-lactide implants in orthopaedic surgery[J].JLong-Term Effects Medical Implants,1997,7:119-37.
[7]Bergsma JE,Bruijin de WC,Rozema FR,Bos RRM,Boering G.Late degradation tissue response to poly(L-lactide) bone plates and screws[J].Biomaterials,1995,16:25-31.
[8]薄颖慧.聚乳酸/羟基磷灰石复合材料的研究[J].中山大学学报(自然科学版),1999,3(38)43.
[9]Clase LE.Mechanical characterrization of biodegradable implants.Clinical materials,1991:10:41-6.
[10].Athansiou KA.Agrawal CM,Barber FA,et al.Orthopaedic applications for PLA-PGA biodegradable polymers.Arthroscopy,1998,14(7):726-37.
[11] Mainil-varlet P. Rahn B, Gogolewski. Long-term in vivo degradation and bone reaction to various polylactides[J]. Biomaterials 1997,(18):257-66.
[12] Tormala P. biodegradable self-rein-forced. Compositematerials , manufactturing structure and mechanical properties[J]. Clinical Materials, 1992,10:29-33.
[13] Rokkanen P, Bostman 0, Vainionpaa S. biodegradable implants in fracture fixation:earl results of treatment of fracture of the ankle. Lancet, 1985,1:1422-30.
[14] Bostman 0. biodegradable internal fixation for malleolar fractures:a prospective randomized trial. JBJS(Br), 1987, 6:1015.
[15].Hollingger JO. Preliminary report on the osteogenic potentional of biodegradable copolymer of Polylactide and polyglycolide., J Biomed Mater Res, 1983, 17:71.
[16] Bostmam P. Foreign-body reactions to polyglycolic screws. Acta orthop scand, 1992.63(2): 173-6.
[17] Heng BC, Cao T, Stanton LW.et al. Strategies for directing the differentiation of stem cells into the osteogentic lingeage in vitro[J].J Bone Miner Res,2004, 19(9)1379-94.
[18] Frank K.Robert P. Matti S. Bioabsorbable interbody cages in a sheep cervical spine fusion model [J]. Spine, 2004, 29(17): 1845-55.
[19] Mike T. Masaka K. Lmai Y. et al. Experience with freeze-dried PGLA/HA2/rhBMP-2 as a bone graft substitute Craniomaxillofac Surg, 2000, 28( 5):294-8.
[20] Frank K,Robert P,Matti S. Bioabsorbable interbody cages in a sheep cervical spine fusion model[J].Spine,2004,29(17):1845-55.
[21] Tormala p, Vasenius J, Vainionpaa S; et al. Utra-high-strength absorbabls self-reinforced polyglycolide (SR-PGA) composite rods for interal fixation of bone fracture in vitro and in vivo study[J]. Biomed Mater Res, 2005, 25(1): 1-22.
[22] ZHAO Ping. Carbon fiber/carbon nano-tubes strengthened calcium phosphate cement composite and its biocompatibility (in Chinese, dis-sertation). Jinan: Shandong University, 2005.
[23] The use of poly-L-lactic acid in lumbar interbody cages; design and biomechanical evaluation in vitro[J].Eur spine,2003,12(10):34-40.
[1]朱青安,胡庆茂,李慧友,等.脊柱三维运动分析系统及其在腰椎稳定性分析中的应用[J].中国脊柱脊髓杂志,1995,5(4):153-6.
[2]McAfee PC.Interbody fusion cages in reconstructive operations on the spine[J].Bone Joint Surg(Am),1999,81(6):859-80.
[3]Van Dijk M,Smit TH,Sugihara S,et al.The effect of Cage stiffness on the rate of lumbar interbody fusion:an in vivo model using poly(1-lactic Acid) and、titanium Cages[J].Spine.2002;27:682-8.
[4]Ray CD.Threaded titanium cages for lumbar interbody fusions [J].Spine,1997,22(6):667-79.
[5]Steffen T,Tsantrizos A,Fruth I,et al.Cages:designs and concepts[J].Eur Spine J,2000,9(Suppl 1):89-94.
[6]Kandziora F,P flugmacher R,Schafer J,et al.Biomechanical comparisons of cervical spine interbody fusion Cages[J].Spine.2001 Sep 1;26(17):1850-7.
[7]Wilke HJ,Kettler A.Primary stabilizing effect of interbody fusion devices for the cervical spine:an in vitro comparison between three different Cage types and bone cement[J].Eur Spine,2000,9(5):410-6.
[8]Kohn J,Langer R.Bioresorbable Material[M].New York:Academic Press,1999.64-73.
[9]Thomas KA.Biomechanics and Biomaterials.[M].Phicadel-phia:WB Saunders,2001.43-51.
[10]Bell GH.Variation in stregth of vertebrae with age and their relation to osteoporosis[J].J Calcif Tissue Res,1967,1(1):75-8.
[11]Yu BS.Biomechanical comparison of the posterolateral fusion and posterior lumbar interbody fusion using pedicle screw fixation system for unstable lumbar spine[J].J Hokkaido Med Sci,2003,78(3):211-8.
[12]黄东生,刘尚礼.椎间盘的生物力学[J].医用生物力学杂志,1997,12(3):175-8.
[13]White AA.Clinical Biomechanics of the Spine[M].Philadelphia:Lippincott,1978.180-4.
[14].Farfan HF.Mechanical disorders of the low back.[M].Philadel-phia:Lea &Febiger,1973.33-5.
[1]Wing KJ,Fisher CG,O'Connell JX,Wing PC.Stopping nicotine exposure before surgery.The effect on spinal fusion in a rabbit model[J].Spine,2000 Jan,25(1):30-4.17.
[2]McLain RF,Yerby SA,Moseley TA.Comparative morphometry of L4 vertebrae:comparison of large animal models for the human lumbar spine 1[J].Spine,2002Apr 15,27(8):E200-6.
[3]Steffen T,Marchesi D,Aebi M.Posterolateral and anterior interbody spinal fusion models in the sheep 1[J].Clin Orthop,2000 Feb,(371):28-37.
[4]Smit TH.The quadruped as an in vivo model for the study of the spine biome -chanical considerations 1[J].Eur Spine J 2002,11:137-144.
[5]Oxland TR,Hoffer Z,Dipling TN,et al.A comparative bio -mechanical investi-gation of anterior lumbar interbody cages:central and bilateral approaches 1[J]Bone Joint Surg Am.2000,82:383-393.
[6]Smit TH,Krijnen MR,Dijk MV,et al.Application of polylactides in spinal cages:Studies in a goat model 1[J].Mater sci:Mater Med 2006 Nov 17(11):1237-1244.
[7]Martijn van,Dijk T H.Smit M,et al.The use of poly-L-lactic acid in lumbar inter-body cages:design and biomechanical evalua-tion l[J].Eur Spin J 2003 12:34-40.
[8]Steffen T,Tsantrizos A,Aebi M Effect of implant design and endplate preparation on the compressive strength of interbody fusion constructs 1[J].Spine 2000,25:1077-1084.
[9]金大地,赵亮,瞿东滨,等.腰椎间盘人工髓核置换术后中期疗效分析.[J].中华骨科杂志,2007,27(5):326-330.
[10]金大地,王吉兴,陈建庭,等.腰椎间盘突出症和椎管狭窄症手术并发症的回顾性分析.[J].中华骨科杂志,2003,24(1):653-656.
[11]Smit TH,Krijnen MR,Dijk van,et al.Application of polylactides in spinal cages;Studies in a goad model 1[J].Mater Sci:Mater Med.2006,17:1237-1244.
[1]Thomas Steffen,Anthony Tsantrizos,Irmgard Fruth,et al.Cages:designs and concepts.[J].Eur spine 2000.9(Suppl 1):89-94.
[2]金大地,赵亮,瞿东滨,等.腰椎间盘人工髓核置换术后中期疗效分析.[J].中华骨科杂志,2007,27(5):326-30.
[3]Kuslich SD,Danielson G,Dowdle JD,et al.Four years follow-up results of lumbar spine arthrodesis using the Bagby and Kus-lick lumbar fusion cage.[J].Spine,2000,25;2656-62.
[4]Bagby GW.Arthrodesis by the distraction-compression method using a stainless steel implant[J].Orthopedics,1988,11:931-34.
[5]Shikinami Y,Okuno M(1999) Bioresorbable devices made of forged composites of hydroxyapatite(HA) particles and poly-1-lactide(PLLA):Part Ⅰ:basic characteristics.Biomaterials 20(9):859-77
[6]Shikinami Y,Okuno M(2001) Bioresorbable devices made of forged composites of hydroxyapatite(HA) particles and poly-1-lactide(PLLA):Part Ⅱ:practica properties of miniscrews and miniplates85-97.
[7]Kulkarni RK,Pani KC,Neuman C,et al:Polylactic acid for surgical implants[J].Arch Surg,1966,93:839-43.
[8]Bostman O.Absorbable implants for the fixation of fracture.J Bone,Joint, Surg,1991,73A:148.
[9]Gogolowski S,Resorbable polymers for intermal fixation,Clinical Material 1992,10-13.
[10]Satavirta S.Immune response to polyglycolic acid implant.JBJS,1990,11:10-13.
[11]Christell.Biodegradable.composites for internal fixation[J].biomaterial,1982,7:271-80.
[12]Gogolowski S,Resorbable polymers for intermal fixation,Clinical Material,1992,8:10-13.
[13]Christel.Biodegradable.composites for internal-fixation.biomaterial,1982,11:271-80.
[14]Tormala P,Pohjonen T.Rokkanen P.Bioresorbable polymers:materials technology and surgi-cal application.Proc Inst Mesh Eng H,1998,212(2):101-2.
[15]Bostman OM,Pihlajamkai HK.Adverse tissue reactions bioabsorbable fixation devices[J].Clin Orthop,2000,371:216-27.
[16]Gerlanch[11.Gerlanch.In-vivo and clinical evalua-tions of poly (L-Lactide)plates and crews for use in maxillofacial traumatology.Clinical material,1993,1:21-4..
[17]吴一民,陈建庭,孙伟,等.珍珠层聚乳酸人工骨的细胞毒性实验.[J].中国临床康复,2002,12(6):1737-1739.
[18]Rozema FR,et al.Influence of re-sorbable poly-(L-Lactide) bone plates and screws on the dose distributions of radiotherapy beams.Int J oral,2006,10(3):135-40.
[19]Hollinger JO.Preliminaryreportonthe osteogenic potential of biodegradable copolymer of polylactide(PLA)and polyglycolide(PGA)[J].BiomedMaster Res,1983,17 : 71-82.
[20]Hollinger JO,Brekke J,Cruskin E,et al.Role of bone substitute [J].Clin Orthop, 1996,(324) : 55-6.
[21] Smith R,TorresA,LiSm,et al. Screening of microorganisms for biodegradation of poly (lactic-acid) and lactic acid containing polymers [J].BiomedMater Res, 1987,21(7) : 991-6.
[22]Martjin VD,Theo HS,Elisabeth HB, et al.Bioabsorbable polyL-lactic acid cages for lumbar interbody fusion:three-year follow-up radiographic,histologic,and histomorphometric analysis in goats[J].Spine,2002,27(23):2706-14.
[23] Caleb RL,Michael H,Bret A,et al. Cervical spine fusion with bioabsorble cages [J]. Neurosurg Focus,2004,16(3) :45 -52.
[24]Smit TH, Burger EH,et al. Bioabsorbable poly-L-lactic acid cages for lumbar interbody fusion: three-year follow-up radiographic, histologic, and histomorphometric analysis in goats [J]. Spine, 2002 ,27 (23):2715-20.
[25] Wuisman P I J, Van Dijk M, Tunc D C, et al. In Vitro and in vivo degradation of bioabsorbable PLLA spinal fusion cages [J]. Biome Mater Res,2002(Appl Biomater),63:752-759.
[26]Smit TH, Krijnen MR, Dijk MV, et al. Application of polylactides in spinal cages: studies in a goat model.[J] Mater Sci: Mater Med 2006 17:1237-44.
[27] Jean Y, Lazennec, Abdallah Madi, Mare A, et al. Evaluation of the 96/4PDLLA polyer resorbable lumbar interbody cage in a long term animal model[J].Eur Spine J 2006 ,15:1545-53.
[28]Eind T, Pflugmacher R, Koch C, et al. Spinal fusion with bioresorbable cages -severe degradation effects. Eur Spine[J]. 2005,14(11):20-3.
[29] Kandziora F, Pflugmacher R, Scholz M, et al Bioabsorbable interrbody cages in a sheep cervical spine fusion model.[J]. Spine 2004,29(3): 1845-55.
[30]Vaccaro AR. Robbins, Madigan L.Early findings in a pilot study of anterior cervical fusion in which bioabsorbable interbody space were used [J]. Neurosurg Focus,2004,16(3): E6.
[31]Lanaman TH. Hopkins TJ.Early findings In a pilot study of anterior cervical interbody fusion in which recombinant human bone morphogeneticprotein- 2 was used with poly(L lactide- co-D. L-lactide) bioabsorbable implants [J]. Neurosurg Focus,2004,16(3):E6.
[32]Subach BR. Haid RR.Roldts CE, et al. Posterior lumbar interbody fusion(PLIF) using an impacted,bioabsorbable device. American Association of Neurological Surgeons, Congress of Neurological Surge-ons:joint section on spinal disorders and peripheral nerves[C]. Orlando. FL. 1999, 12: 113-20..
[33]Couture DE, Branch CL. Posterior lumbar interbody fusion with bioabsorbable spacers and local autograft in a series of 27 patients[J]. Neurosurg Focus,2004, 16(3):E8.
[34]Lanman TH. Hopkins TJ.Lumbar interbody fusion after treat- ment with recombinant human bone morphogenetic protein- 2 added to poly ( L- lactide- co- D, L- lactide) bioresorbable im-plants[J] .Neurosurg Focus, 2004, 16(3):E9.
[35]Coe JD. Vaccaro AR.Instrumented transforaminal lumbar interbody fusion with bioresorbable polymer implants and iliac crest autograft[J]. Spine, 2005, 30(Suppl 17):76-83.
[36]Heng BC, Cao T, Stanton LR.et al. Strategies for directing the differentiation of stem cells into the osteogenic lineage in vitro [J]. Bone Miner Res,2004,19(9): 1379-94.
[37] Mike T. Maeaka K. l,mai Y. et al. Experience with freeze-dried PGLA/HA2/rhBMP-2 as a bone graft substitute[J]. Craniomaxillofac Surg,2000,28(5):294-8.
[38]Caleb RL.Michael H.Rret A.et al.Cervical spine fusion with bioabsorble cages[J].Neurosurg Focus,2004,16(3):E4..