新型低弹β钛合金植入物—骨界面成骨效应研究
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摘要
背景:
临床上作为外科植入用的金属生物材料中,钛及钛合金由于具有优良的生物相容性和优异的机械性能以及在体液环境中的耐腐蚀性而获得了广泛应用。但植入物与骨之间弹性模量的不匹配问题仍未彻底解决,目前已有的生物医用钛合金由于弹性模量与人骨相比过高,会导致载荷不能由植入物很好地传递到相邻骨组织,出现“应力屏蔽”现象,从而使植入物周围出现骨吸收,引起内植物松动或断裂,最终造成植入物的失败。因此尽可能的将载荷均匀地传到周围骨组织,减少“应力屏蔽”效应,是植入物成功与否的重要条件。因而研究具有较低弹性模量的新型生物医用钛合金就成为当前研究的热点。目前临床广泛使用的Ti-6Al-4V弹性模量为110GPa,虽然已经低于不锈钢的(200Gpa),可相比于人骨骼等硬组织的10-30GPa,仍然较高,近期中国科学院金属研究所研制的Ti-24Nb-4Zr-7.9Sn系低弹性模量医用钛合金,弹性模量低至30GPa,更接近皮质骨的弹性模量,而屈服强度达到800-900MPa,明显优于临床现有的钛合金材料,有望成为为临床上替代原有钛金属材料的一种新型材料。
目的:
本研究目的是了解两种不同弹性模量(Ti–24Nb–4Zr–7.9Sn,弹性模量30GPa和Ti-6Al-4V,弹性模量110GPa)钛合金内植物对界面骨形成和界面应力分布的影响。
方法:
选用成年新西兰大白兔30只,采用Slaets E方法于双侧胫骨内侧近端植入两种弹性模量钛合金植入物,其中左侧为低弹组(Ti-24Nb-4Zr-7.9Sn,弹性模量30GPa),右侧为高弹组(Ti-6Al-4V,弹性模量110GPa),分别于术后4、8、12周分别处死9只动物,采用X线、组织学、生物力学及Micro-CT对标本进行评价。Micro-CT检测指标包括BMD,BVF,SMI,兴趣区选择以植入物为中心的一个半径1mm的管状区域。组织学监测指标包括:骨接触率(BCR)、骨形成率(BFR),兴趣区选择以植入物选择植入物横断面上,以植入物为中心的周围半径为0.5mm的环状区域。
结果:
X线:4、8、12周X线显示无明显差异。组织学:4、8、12周组织学切片显示4、8、12周时低弹组BCR均明显高于高弹组(P<0.05)。4周时两组的BFR无显著性差异(P>0.05),8、12周时低弹组BFR高于高弹组(P<0.05)。
Micro-CT:4周时,两组的BMD,BVF,SMI,AS无显著性差异(P>0.05),8、12周时低弹组BMD,BVF,SMI,AS均明显优于高弹组(P<0.05)。生物力学检测:4周时低弹组的Fmax高于高弹组但无显著性差异(P>0.05),8、12周时低弹组Fmax明显高于高弹组(P<0.05)。
结论:
本研究中,新型低弹β钛合金Ti-24Nb-4Zr-7.9Sn内植物,相比于临床常用的Ti-6Al-4V内植物,能将更多的应力均匀的传递到周围骨组织中去,降低了应力集中效应,减少了骨组织的吸收,有利于植入物-骨界面的新骨形成,提高了骨界面的接触率,有利于骨整合,从而提高植入物的生物稳定性。我们相信,新型低弹β钛合金将在骨科领域有更广阔的应用。
Background:
Because of their outstanding biocompatibility and mechanical function, excellent corrosion resistance to biological environments, Titanium (Ti) and its alloys have been widely utilized in medical practice, Nevertheless, there is still a problem that the difference of elastic modulus between implants and bone tissue exists. At present the Ti and its alloys used in clinic have higher elastic modulus than bones, and it will affect transferring the stress to the bone. The significant difference in elastic modulus between implants and bone tissue can lead to stress shielding effect, and thereby may cause bone absorption or poor osseointegration. To achieve the success it is very important to control the stress shielding effect and try the best to transfer the stress to the bone. Therefore, the study of Ti and its alloys with a low elastic modulus become more and more hotter. The implants with a low elastic modulus shares loads with the bone to facilitate bone growth. Now the clinically used Ti–6Al–4V has an elastic modulus of 110GPa, which is lower than 200GPa of stainless steel, but still higher than 10-30 GPa of natural bone. Ti–24Nb–4Zr–7.9Sn is a newβ-type titanium alloy developed recently for biomedical application. It shows higher strength(800-900MPa) than that of Ti-6Al-4V(600MPa),and relatively lower elastic modulus(33GPa).It may be a new substitute material used for biomedical application in the future.
Objective:
To investigate the influence of implants on new bone formation and the effects of stress distribution on the interface with two different elastic modulus. (Ti–24Nb–4Zr–7.9Sn with modulus of elasticity about 30GPa and Ti-6Al-4V with modulus of elasticity about 110GPa).
Methods:
Thirty adult New Zealand white rabbits were selected in this study. Two different kinds of modulus of elasticity titanium alloy implants were inserted into proximal tibia by Slaets’method. The left lateral tibia was low elastic modulus group (Ti–24Nb–4Zr–7.9Sn,modulus of elasticity about 30GPa ). The right one was high elastic modulus group (Ti-6Al-4V,modulus of elasticity about 110GPa)., After surgery, 9 animals were sacrificed respectively at 4 weeks, 8 weeks, 12 weeks , X-ray, histology, biomechanics and micro-CT were used to observe the results. The tubiform region were defined as the region of the interest 1 (ROI1) of which the center is the implant and the radius is 1mm. The Anisotropy (AS), bone mineral density (BMD), bone volume fraction (BVF) and structure model index (SMI) had been analyzed in ROI1 by Micro-CT. In the histology the orbicular region on the middle cross section of the implants were defined as the ROI2, of which the center is the implants and the radius is 0.5mm. The bone formation ratio (BFR) and bone contact ratio (BCR) had been analyzed in ROI2.
Results:
X-ray examination: X-ray films of 4, 8, 12 weeks after operation show no significant difference between the low elastic modulus group and the high elastic modulus group.
Histological examination: In the ROI2, at the 4, 8, 12 weeks after the operation, the BCR of the low elastic modulus group have better performance than high elastic modulus group (P<0.05). At the 4 weeks after the operation, the BFR of the two groups shows no difference, and at the 8 and 12 weeks after the operation, BFR of the low elastic modulus group have better performance than high elastic group (P<0.05).
Micro-CT: in the ROI1, at the 4 weeks after the operation, the BMD, BVF, SMI and AS show no obviously differences between the two groups. At 8 weeks and 12 weeks after the operation, the BMD,BVF, SMI and AS show the significant differences between the two groups and the low elastic modulus group is obviously better than the high elastic modulus group(P<0.05).
Biomechanics test: At 4 weeks after the operation the maximum force (Fmax) of the low elastic modulus group is higher than the high elastic modulus group but there are no significant differences between two groups. At 8 weeks and 12 weeks after the operation, the Fmax of the low elastic modulus group is significant higher than the high elastic modulus group.
Conclusion:
In our study, the new low elastic modulusβTi alloy implants of Ti-24Nb-4Zr-7.9Sn, compared with Ti-6Al-4V used in clinic, permits more stress to be transmitted into bones ,results in less stress concentrated and less bone resorption. It is better for new bone formation in the interface and improving the bone contact radio, so it will be easy to achieve osseointegration, and help to enhance the biological stability. We believe that the new low elastic modulusβTi alloy will have a bright prospect of orthopedic applications.
临床上作为外科植入用的金属生物材料中,钛及钛合金由于具有优良的生物相容性和优异的机械性能以及在体液环境中的耐腐蚀性而获得了广泛应用。但植入物与骨之间弹性模量的不匹配问题仍未彻底解决,目前已有的生物医用钛合金由于弹性模量与人骨相比过高,会导致载荷不能由植入物很好地传递到相邻骨组织,出现“应力屏蔽”现象,从而使植入物周围出现骨吸收,引起内植物松动或断裂,最终造成植入物的失败。因此尽可能的将载荷均匀地传到周围骨组织,减少“应力屏蔽”效应,是植入物成功与否的重要条件。因而研究具有较低弹性模量的新型生物医用钛合金就成为当前研究的热点。目前临床广泛使用的Ti-6Al-4V弹性模量为110GPa,虽然已经低于不锈钢的(200Gpa),可相比于人骨骼等硬组织的10-30GPa,仍然较高,近期中国科学院金属研究所研制的Ti-24Nb-4Zr-7.9Sn系低弹性模量医用钛合金,弹性模量低至30GPa,更接近皮质骨的弹性模量,而屈服强度达到800-900MPa,明显优于临床现有的钛合金材料,有望成为为临床上替代原有钛金属材料的一种新型材料。
目的:
本研究目的是了解两种不同弹性模量(Ti–24Nb–4Zr–7.9Sn,弹性模量30GPa和Ti-6Al-4V,弹性模量110GPa)钛合金内植物对界面骨形成和界面应力分布的影响。
方法:
选用成年新西兰大白兔30只,采用Slaets E方法于双侧胫骨内侧近端植入两种弹性模量钛合金植入物,其中左侧为低弹组(Ti-24Nb-4Zr-7.9Sn,弹性模量30GPa),右侧为高弹组(Ti-6Al-4V,弹性模量110GPa),分别于术后4、8、12周分别处死9只动物,采用X线、组织学、生物力学及Micro-CT对标本进行评价。Micro-CT检测指标包括BMD,BVF,SMI,兴趣区选择以植入物为中心的一个半径1mm的管状区域。组织学监测指标包括:骨接触率(BCR)、骨形成率(BFR),兴趣区选择以植入物选择植入物横断面上,以植入物为中心的周围半径为0.5mm的环状区域。
结果:
X线:4、8、12周X线显示无明显差异。组织学:4、8、12周组织学切片显示4、8、12周时低弹组BCR均明显高于高弹组(P<0.05)。4周时两组的BFR无显著性差异(P>0.05),8、12周时低弹组BFR高于高弹组(P<0.05)。
Micro-CT:4周时,两组的BMD,BVF,SMI,AS无显著性差异(P>0.05),8、12周时低弹组BMD,BVF,SMI,AS均明显优于高弹组(P<0.05)。生物力学检测:4周时低弹组的Fmax高于高弹组但无显著性差异(P>0.05),8、12周时低弹组Fmax明显高于高弹组(P<0.05)。
结论:
本研究中,新型低弹β钛合金Ti-24Nb-4Zr-7.9Sn内植物,相比于临床常用的Ti-6Al-4V内植物,能将更多的应力均匀的传递到周围骨组织中去,降低了应力集中效应,减少了骨组织的吸收,有利于植入物-骨界面的新骨形成,提高了骨界面的接触率,有利于骨整合,从而提高植入物的生物稳定性。我们相信,新型低弹β钛合金将在骨科领域有更广阔的应用。
Background:
Because of their outstanding biocompatibility and mechanical function, excellent corrosion resistance to biological environments, Titanium (Ti) and its alloys have been widely utilized in medical practice, Nevertheless, there is still a problem that the difference of elastic modulus between implants and bone tissue exists. At present the Ti and its alloys used in clinic have higher elastic modulus than bones, and it will affect transferring the stress to the bone. The significant difference in elastic modulus between implants and bone tissue can lead to stress shielding effect, and thereby may cause bone absorption or poor osseointegration. To achieve the success it is very important to control the stress shielding effect and try the best to transfer the stress to the bone. Therefore, the study of Ti and its alloys with a low elastic modulus become more and more hotter. The implants with a low elastic modulus shares loads with the bone to facilitate bone growth. Now the clinically used Ti–6Al–4V has an elastic modulus of 110GPa, which is lower than 200GPa of stainless steel, but still higher than 10-30 GPa of natural bone. Ti–24Nb–4Zr–7.9Sn is a newβ-type titanium alloy developed recently for biomedical application. It shows higher strength(800-900MPa) than that of Ti-6Al-4V(600MPa),and relatively lower elastic modulus(33GPa).It may be a new substitute material used for biomedical application in the future.
Objective:
To investigate the influence of implants on new bone formation and the effects of stress distribution on the interface with two different elastic modulus. (Ti–24Nb–4Zr–7.9Sn with modulus of elasticity about 30GPa and Ti-6Al-4V with modulus of elasticity about 110GPa).
Methods:
Thirty adult New Zealand white rabbits were selected in this study. Two different kinds of modulus of elasticity titanium alloy implants were inserted into proximal tibia by Slaets’method. The left lateral tibia was low elastic modulus group (Ti–24Nb–4Zr–7.9Sn,modulus of elasticity about 30GPa ). The right one was high elastic modulus group (Ti-6Al-4V,modulus of elasticity about 110GPa)., After surgery, 9 animals were sacrificed respectively at 4 weeks, 8 weeks, 12 weeks , X-ray, histology, biomechanics and micro-CT were used to observe the results. The tubiform region were defined as the region of the interest 1 (ROI1) of which the center is the implant and the radius is 1mm. The Anisotropy (AS), bone mineral density (BMD), bone volume fraction (BVF) and structure model index (SMI) had been analyzed in ROI1 by Micro-CT. In the histology the orbicular region on the middle cross section of the implants were defined as the ROI2, of which the center is the implants and the radius is 0.5mm. The bone formation ratio (BFR) and bone contact ratio (BCR) had been analyzed in ROI2.
Results:
X-ray examination: X-ray films of 4, 8, 12 weeks after operation show no significant difference between the low elastic modulus group and the high elastic modulus group.
Histological examination: In the ROI2, at the 4, 8, 12 weeks after the operation, the BCR of the low elastic modulus group have better performance than high elastic modulus group (P<0.05). At the 4 weeks after the operation, the BFR of the two groups shows no difference, and at the 8 and 12 weeks after the operation, BFR of the low elastic modulus group have better performance than high elastic group (P<0.05).
Micro-CT: in the ROI1, at the 4 weeks after the operation, the BMD, BVF, SMI and AS show no obviously differences between the two groups. At 8 weeks and 12 weeks after the operation, the BMD,BVF, SMI and AS show the significant differences between the two groups and the low elastic modulus group is obviously better than the high elastic modulus group(P<0.05).
Biomechanics test: At 4 weeks after the operation the maximum force (Fmax) of the low elastic modulus group is higher than the high elastic modulus group but there are no significant differences between two groups. At 8 weeks and 12 weeks after the operation, the Fmax of the low elastic modulus group is significant higher than the high elastic modulus group.
Conclusion:
In our study, the new low elastic modulusβTi alloy implants of Ti-24Nb-4Zr-7.9Sn, compared with Ti-6Al-4V used in clinic, permits more stress to be transmitted into bones ,results in less stress concentrated and less bone resorption. It is better for new bone formation in the interface and improving the bone contact radio, so it will be easy to achieve osseointegration, and help to enhance the biological stability. We believe that the new low elastic modulusβTi alloy will have a bright prospect of orthopedic applications.
引文
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60. Shtansky,-D-V, Gloushankova,-N-A et al. Design, characterization and testing of Ti-based multicomponent coatings for load-bearing medical applications. Biomaterials. 2005 Jun; 26(16): 2909-24.
61. Uhthoff HK, Bardos DI, Liskova-Kiar M. The advantages of titanium alloy over stainless steel plates for the internal fixation of fractures. An experimental study in dogs. J Bone Joint Surg Br 1981;63B:427–84.
62. Sumner DR, Turner TM, Igloria R, Urban RM, Galante JO. Functional adaptation and ingrowth of bone vary as a function of hip implant stiffness. J Biomech 1998;31:909-917.
63. Gasser B. Design and engineering criteria for titanium devices. In: Brunette DM, Tengvall P, Textor M, Thomsen P, editors. Titanium in medicine. Berlin: Springer; 2001. p. 674.
64. Huiskes R,Weinans H , Van Rietbergen B.The relationship between stress shielding and bone resorption around total hip stems and the effects of flexible materials.Clin Orthop,1992; 274:124.
65. Davies JE.In ViLr0 Modeling of the Bone/Implant Interface.The Anatomical Record. 1996, 245: 426-445. -42-
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67. Matsuno H, Yokoyama A, Watari F, et al. Biocompatibility and osteogenesis of refractory metal implants, titanium, hafnium, niobium, tantalum and rhenium. Biomaterials 2001; 22: 1253-62.
68. M. Franchi, M. Fini, D. Martini,et al. Biological fixation of endosseous implants, Micron. 2005; 36(7-8):665-71.