【作者】 石磊；

【导师】 雷伟；

【作者基本信息】 第四军医大学 ， 外科学， 2011， 博士

【副题名】构建表面具有生物活性的低弹性模量的膨胀式椎弓根螺钉

【摘要】 在骨质疏松(Osteoporosis, OP)条件下,椎弓根螺钉与周围骨质结合强度明显下降,螺钉松动、移位、脱出等并发症时有发生。为了提高螺钉稳定性和减少并发症的发生,许多学者采用各种方法对螺钉行强化处理,均取得了一定的效果。近年来一些学者开始使用膨胀式椎弓根螺钉来提高螺钉的稳定性,通过螺钉的机械性膨胀,增加螺钉在椎体内与骨的接触面积,增大钉-骨界面的摩擦力,从而提高了螺钉的稳定性。本课题组在前期研究工作中,自行研制开发了一种新型的膨胀式椎弓根螺钉,在动物体内外实验及临床初步应用中均取得了良好的疗效。但是由于螺钉自身材质弹性模量远远高于骨组织的弹性模量,特别是在OP条件下,这种螺钉与骨组织的弹性模量的不匹配更加明显,可能会导致应力不能很好的传递到螺钉周围骨质中去,从而产生“应力遮挡”效应,造成螺钉周围骨质吸收,增加螺钉松动的可能。同时由于螺钉自身材质本身不具有生物活性,因而在螺钉-骨界面上,只能发生机械性的锚合而不可能发生生物化学性的嵌合,因此降低了螺钉-骨界面的结合强度,从而增加了螺钉潜在松动的可能。目的:1.研究低弹性模量椎弓根螺钉对改善螺钉固定强度的作用;2.研究微弧氧化表面改性的椎弓根螺钉对提高螺钉固定强度的作用。方法:1.将普通椎弓根钉(pedicle screw, PS),膨胀椎弓根螺钉(expandable pedicle screw, EPS)和低弹性模量(Ti24Nb4Zr7.9Sn, 42GPa)膨胀椎弓根螺钉(low elastic modulus expandable pedicle screw, L-EPS)以相同的方法制备钉道,植入OP生物力学模块后,行X线检查和轴向拔出实验;2.将EPS和L-EPS植入OP绵羊体内12周后,行轴向拔出实验,Micro-CT分析和组织学分析;3.检测经MAO处理后材料表面的特征,并将大鼠成骨细胞(osteoblasts, OB)接种于材料试件表面,观察OB在试件表面粘附、增值和分化能力;4.将MAO处理的L-EPS(MAO treated L-EPS,MAO-L-EPS)和L-EPS植入OP绵羊体内12周后,行轴向拔出实验、Micro-CT分析和组织学观察。结果:1.OP骨质疏松模块实验中,L-EPS组和EPS组之间的最大轴向拔出力(the maximum pullout strength, Fmax)和能量吸收值(energy absorbed to failure, E)均显著高于PS组(P < 0.05),但是两组之间无统计学差异(P > 0.05);2.在OP绵羊体内植入实验中,L-EPS组的Fmax和E均显著高于EPS组(P < 0.05),同时Micro-CT检测和组织学检测显示L-EPS组螺钉周围及膨胀缝隙内骨小梁结构、密度均显著优于EPS组(P < 0.05);3.经过MAO处理,在材料表面形成一层均一的、多孔的富含Ca、P元素的氧化膜,成骨细胞在其表面的增值、粘附和分化能力均显著优于未处理组(P < 0.05);4.OP绵羊体内植入实验中,MAO-L-EPS组的Fmax和E均显著高于L-EPS组(P < 0.05),Micro-CT检测和组织学检测显示大量骨小梁在MAO-L-EPS组周围形成,在骨小梁数量和质量上均优于L-EPS组(P < 0.05),扫描电镜(Scaning electron microscope,SEM)检测显示,MAO-L-EPS较L-EPS有更好的钉-骨界面,与骨组织结合更加紧密。结论:1.L-EPS和EPS一样都能较PS显著提高螺钉的稳定性;2.L-EPS通过降低螺钉的弹性模量,减少了因为螺钉与骨质弹性模量不匹配而导致的“应力遮挡”效应,使应力能够更好的传递到螺钉周围的骨质中去,促进了螺钉周围骨质的生长,减少了螺钉周围骨质的吸收,提高了螺钉在骨组织中的稳定性,从而有利于螺钉在生物体内的长期生存;3.经过MAO处理的材料,其表面形成的特异性的氧化膜,有利于成骨细胞的粘附、增值和分化。4.MAO-L-EPS通过MAO处理提高了螺钉表面的生物活性,使得螺钉与周围骨组织的结合从单一的机械性锚合模式变成了机械性锚合和生物化学性键合相结合的复合型结合模式,这种复合性钉-骨界面结合模式有利于进一步提高了螺钉的稳定性;5.从PS到EPS,再从EPS到L-EPS,最后从L-EPS到MAO-L-EPS,我们成功构建了新型椎弓根螺钉,其良好的机械性能以及优秀的表面生物活性,使其在临床应用成为可能。更多还原

【Abstract】 The bonding strength of pedicle screw is significantly decreased in the osteoporosis (OP), which results in screw loosening, migration or back-out. In order to enhance the stability of the screw and limit the complications, many methods have been used. Resent years, some researchers have used expandable pedicle screw to increase the stability of screw. Due to the mechanical expansion, the bone-screw contact and friction are increased, which improves the stability of the screw. In our previous studies we designed a novel expandable pedicle screw (EPS), and it was proved that the EPS can significantly improve the stability of the screw in both experiments and clinical practices.However, the elastic modulus of screw is much higher than that of bone tissue, and the modulus mismatch will be more obvious in the OP, which causes“stress shielding effect”, peri-screw bone resorption, and finally screw loosening. Moreover, the material of screw has no bioactivity, so that only mechanical intergration not including biochemical bonding can be formed at the screw-bone interface, which decreases the bonding strength of the screw-bone interface and increases the possibility of screw loosening.Objective: 1. to study the impact of low elastic modulus on the fixation of pedicle screw; 2. to study the impact of micro-arc oxidation on the fixation of pedicle screw.Methods: 1. After the pedicle screw (PS), expandable pedicle screw (EPS) and low elastic modulus (Ti24Nb4Zr7.9Sn, 42GPa) expandable pedicle screw (L-EPS) were implanted into the OP biomechanical tests block through the prepared pilot holes, the X-ray and axial pull-out tests were performed; 2. The EPS and L-EPS were inserted into the OP sheep spine, after 12 weeks implantation, the axial pull-out tests, Micro-CT analysis and histological observation were performed; 3. The features of micro-arc oxidation (MAO) treated surface were detected, the osteoblasts (OB) were seeded onto the MAO treated disks and the adhesion, prolification and differentiation abilities of the OB were observed, moreover, the bone formation genes were also detected; 4. The MAO treated L-EPS (MAO-L-EPS) and L-EPS were put into the OP sheep spine, after 12 weeks implantation, the axial pull-out tests, Micro-CT analysis and histological observation were performed.Results: 1.In OP biomechanical tests block, the maximum pull-out strength (Fmax) and energy absorbed to failure (E) in EPS and L-EPS groups were significantly higher than those in PS group (P < 0.05), but there was no significant difference in both Fmax and E between EPS and L-EPS groups (P > 0.05); 2. In OP sheep spine, the Fmax and E in L-EPS were significantly higher than those in EPS group (P < 0.05), Micro-CT analysis and histological observation showed that the density and structure of trabecular bone in L-EPS group were superior to those in EPS group (P < 0.05). 3. After the MAO treated, a homogeneous, polyporous oxided coating with Ca and P elements was formed onto the surface of materials. The adhesion, prolification and differentiation abilities of the OB were significantly improved after seeded onto the MAO treated group compared to untreated group (P < 0.05). 4. In OP sheep spine, the Fmax and E in MAO-L-EPS were significantly higher than those in L-EPS group (P < 0.05). A large of newly formed trabecular bone was detected in MAO-L-EPS group, which was better in both quantity and quality than those in L-EPS group (P < 0.05), moreover the better screw-bone interface was found in MAO-L-EPS group compared to L-EPS group.Conclusions:1.Compare with PS, the L-EPS and EPS can significantly improve the stability of the screw.2.With low elastic modulus, the L-EPS reduces the“stress shielding effect”caused by mismatch of the modulus between screw and bone tissue and makes the stress transferred into the peri-screw bone tissue. This encourages the bone formation, reduces the peri-screw bone resorption, enhances the stability of screw and longens the screw survival time.3.After MAO treated, a special oxide coating is formed which is benefit for OB to adhere, proliferate and differentiate.4.After MAO treated, the bioactivity of MAO-L-EPS is significantly improved, which makes the screw-bone bonding changed from single mechanical intergration to mechanical and biochemically combined intergration. This combined intergration will further improve the stability of the screw.5.From PS to EPS, EPS to L-EPS, and L-EPS to MAO-L-EPS, we have successfully established a novel pedicle screw which maybe use in the clinical practice owning to its superior mechanical properties and superficial bioactivity.更多还原