HA/PMMA复合活性骨水泥椎体成形的实验和临床研究
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摘要
引言
经皮穿刺椎体成形最早用来治疗转移瘤和血管瘤。现在作为微创手术广泛运用于椎体压缩性骨折。临床报告显示70—80％椎体成形患者疼痛缓解。在强化椎体时临床运用最多是甲基丙稀酸甲脂(PMMA)，其存在主要缺陷是骨相容性欠佳，不能和骨表面有较强的结合，以及聚合温度较高；试验证明在PMMA中添加具有活性成分的羟基磷灰HA石可以明显改善生物活性。在椎体成形的生物力学研究多集中在胸腰椎的单个椎体或单个脊柱单元的测试，试验证明成形后明显增强椎体的最大压缩力或强度、刚度。本试验测试添加了HA的PMMA骨水泥的力学性能变化，并在以下几个方面测试：从椎体局部终板受力角度，评估强化后对终板力学分布的影响；从胸腰椎骨折后椎体重建的角度，评估填塞式成形在胸腰椎骨折后重建椎体的生物力学改变；在颈椎行椎体成形用来治疗转移瘤和血管瘤已经有报道，本试验测试强化后对颈椎骨折抗压缩力和刚度影响，为临床提供参考数据。从脊柱单元整体角度，评估椎体成形对胸腰椎骨折三维稳定性的影响。
胸腰椎压缩性骨折手术治疗后椎体复位后会形成空心椎，增加内固定断裂的危险，远期椎体高度的丢失，后突畸形，引起顽固性腰背痛。由于伤椎内植骨的随访结果并不愈合，有学者尝试伤椎用骨水泥椎体成形，试图减少内固定应力，避免椎体塌陷。本研究在临床针对胸腰椎爆裂性骨折患者在椎弓根内固定的基础上，采用羟基磷灰石／聚甲基丙烯酸甲酯(HA／PMMA)骨水泥进行椎体内灌注，重建了椎体高度、强度、刚度、脊柱矢状位序列，并进行临床评估。
第一部分H刀pMMA活性骨水泥椎体成形的生物力学研究
目的:
1.评估添加不同含量的队后P珊认刚度和强度变化，以及凝固时间对
力学特性影响。
2.评估10%HA/P呱从椎体成形对老年椎体标本终板应力分布的影响。
3.评估10%HA/P呱从填塞式(Tamp)椎体成形，即在骨水泥粘度较大
时直接经椎弓根通道捣塞到椎体内，与常规注射式(Injection)椎体成
形比较，测试的压缩力和刚度变化。
4.评估颈椎在10%HA/P呱认骨水泥椎体成形后强度和刚度的变化。
5.评估10%HA/P呱认在胸腰椎骨折后椎体成形对恢复脊柱三维稳定
性的作用。
方法:
1.将纯PMMA组、10%HA/P MMA(WT)组、20%HA/P MMA(盯)组、CPC
组等四组材料，分别制成直径gllun，高10llnn的圆柱状，聚合后1小时、24
小时压缩试验，0.5。/min，压缩Zllnn，测量强度和刚度。
2.四具新鲜骨质疏松胸腰段脊柱标本(T12~L4)。X线排除腰椎骨折
或肿瘤，测量骨密度。分离后仅剩椎体和终板，随机分成对照组和椎体
成形组。在终板中心，按顺时钟座标方向，距离边缘皮质骨7咖，取9个
点，用直径2.3Inln的半球形压头以0.03nun/s的速度，下压3Inln。力与位
移曲线可计算出最大压缩力及刚度。比较终板不同位点的最大压缩力及
刚度分布差异。两组内椎体终板在相同点最大压缩力及刚度进行比较。
3.四具新鲜骨质疏松胸腰段脊柱标本(Tll~L4)。经正侧位X线排
除骨折或肿瘤，选16个椎体节段，测量骨密度。分离后仅剩下椎体和终
板，随机分成注射式成形组(Inje。t ion)和填塞式椎体成形组(Tamp)。
Slnln/min压缩6毫米或载荷一变形曲线出现了最高点，10Hz频率记录。10
%HA/PMMA行椎体成形。Injection组:经椎弓根11G的骨穿针，注射。
Tamp组:用6Inlll钻头通过椎弓根，插入5.Slnm导入棒，上下撬拨，骨水
泥为橡皮泥样，用导入棒将骨水泥塞入到椎体中。初始和处理后2小时
分别压缩。计算最大压缩力和刚度。可重复测量的方差分析处理数据。
4.三具新成年男性颈椎标本(C4一6C)，选择9个椎体节段，骨密度测
一3一
量正常。分离仅剩下椎体和终板，以Slnln/min压缩4毫米或椎体的负载
压力出现下降。10%HA/P呱认骨水泥自前椎体正中用11G的骨穿针，进
入约1一1.scm，注射2一3ml。固化2小时后再压缩。计算在位移3llnn时
的压缩力、最大压缩力、最大压缩力的位移和刚度。
5.七具新鲜胸腰段脊柱标本(T12~L5)，用聚甲基丙烯酸甲酷平行包
埋标本的两端，在三位运动试验机上测试标本的前屈、后伸、左侧弯、右
侧弯、左旋转、右旋转，加载0一SNM，用三维显微激光扫描仪采集图象。
测量正常、骨折后、伤椎椎体成形后、疲劳测试后的中性区和运动范围。
骨折模型制备:在Ll椎体前中间用3llun的钻头，深度Icm，在MTS试验
机上屈曲12度，在1秒内压缩力迅速提升到10KN，至椎体骨折。10%
队/P枷A骨水泥经双侧椎弓根每侧灌注4ml，共8~9毫升，固化2小时
后测试。疲劳测试:屈曲12度，屈曲加载SNm，扭转加载SNm，频率0.SHz，
疲劳3000次循环。采用重复测量方差分析，LSN方法两两比较。
结果:
1.在P枷A中添加10%HA组强度减少9.14%，刚度减少了10.17%，
20%HA组强度减少38.26%，刚度减少了48.82%，CPC骨水泥的强度只有纯
PMMA的6.92%，刚度只有10.84%。前三组1小时和24小时聚合后比较无差
别。
2.椎体终板的测试显示两组的骨密度近似，无显著性差异。最大压
缩力时的位移，正常组对照组1.33士0.44llnn，在椎体成形组 1.51士0.48llun，
组内各位点无明显差别，两组间无差
1. To determine whether the incorporation of HA in a PMMA matrix would enhance the effect of mechanical as compared to PMMA and CPC.
2.To determine the effect of endplate on the distribution structural properties with 10%HA/PMMA vertrbroplasty.
3.To compare the biomechanical properties of isolated, fractured osteoporotic vertebral bodies treated by tamp vertebroplasty or injection vertebroplasty.
4.To determine the strength and stiffness of cervical vertebral bodies subjected to compression fractures and subsequently stabilized via anterior injection of 10% HA/PMMA cement.
5.PMMA has long been in the stabilization and reconstruction of traumatic and pathological fracture of the spine. And now 10%HA/PMMA, an osteoconductive, biocompatible cement, has use as an alternative to PMMA. In this study is to determine the stabilizing effects of 10%HA/PM MA in an experimental compression fraction of Lumbar.
Methods.
1. PMMA circular cylinder, diameter 10mm and height 9mm,with 0, 10 and 20 % HA, were compressed in a materials test machine to dermine strength and stiffness in one or 24 hour.
2.The bony endplates of four intact human osteoporotic disintegrating vertebrae (T12-L5) were tested. Indentation tests were performed at
-9-
standardized test on the endplate of both contrast normal group and vertebriplasty with 10%HA/PMMA by using a 2.3-mm diameter, hemispherical indenter with a test rate of 0.2 mm/s to a depth of 3 mm. The failure load and stiffness at each site were determined from the load-displacement curves. Repeated measures analyses were used to analyze the resulting data for variation in the anterior-posterior and lateral directions, as well as to determine the effect of vertebroplasty.
3.Compression fractures were experimentally created in 4 osteoporotic VBs assigned to either the tamp or vertebroplasty group. The tamp treatment consisted of inserting 6mm drill into pedicle of vertebral body. A diameter 5mm stick raised the endplate, and filling the void with 10%HA/PMMA cement bone .The vertebroplasty treatment consisted of directly injecting 10%HA/PMMA cement into the vertebral body. The repaired vertebral bodies were recompressed to determine post treatment strength and stiffness values.
4.Three vertebral bodies (C4-C6) from three fresh spines harvested from adult male cadavers, were disarticulated, and compressed in a materials testing machine to determine initial strength and stiffness. The fractures then were repaired using an anterior injection of 10%HA/PMMA and recrushed to determine post treatment strength and stiffness values.
5.Seven T11-L5 cadaveric spinal specimens were mounted individually on test fram. The cubes were placed on the vertebra by a pin. Motion was tracked by 3D digital microscopic laser in response to applied loads of 0 to 8 Nm. The compressive impact technique was used to induce a reproducible compression fracture of L-l after partially coring out the vertebra. Load testing was performed on the intact spine. Postfracture, after bipedicular transpedicular vertebroplasty with 8 ml of 10%HA/PMMA and after flexion-extension fatiguing to 3000 cycles at 5 Nm. Ranges of motion and neutral zones were measured.
Results.
1. The addition of 10% wt and 20 % HA caused a signigcant decrease in
-1
0-
strength about 9.14% and 40%, in stiffness 10.17% and 48.82%. There is no difference between 1 hour and 24 hour. CPC cement strength is only 6.92% of PMMA alone.
2.For the contrast group endplates, both the failure load and stiffness varied significantly across the endplate surfaces, without the poster lateral regions being stronger and stiffer than other except the central regions. The central regions are lowest. On vertebroplatsty endplate, the mean failure load and stiffness increased significantly with the posterolateral regions being weaker and lower than others. The central regions are strongest.
3.Both treatments resulted in significantly stronger vertebral bodies relative to their initial state. The vertebroplasty treatment restored vertebral body stiffness to initial values
经皮穿刺椎体成形最早用来治疗转移瘤和血管瘤。现在作为微创手术广泛运用于椎体压缩性骨折。临床报告显示70—80％椎体成形患者疼痛缓解。在强化椎体时临床运用最多是甲基丙稀酸甲脂(PMMA)，其存在主要缺陷是骨相容性欠佳，不能和骨表面有较强的结合，以及聚合温度较高；试验证明在PMMA中添加具有活性成分的羟基磷灰HA石可以明显改善生物活性。在椎体成形的生物力学研究多集中在胸腰椎的单个椎体或单个脊柱单元的测试，试验证明成形后明显增强椎体的最大压缩力或强度、刚度。本试验测试添加了HA的PMMA骨水泥的力学性能变化，并在以下几个方面测试：从椎体局部终板受力角度，评估强化后对终板力学分布的影响；从胸腰椎骨折后椎体重建的角度，评估填塞式成形在胸腰椎骨折后重建椎体的生物力学改变；在颈椎行椎体成形用来治疗转移瘤和血管瘤已经有报道，本试验测试强化后对颈椎骨折抗压缩力和刚度影响，为临床提供参考数据。从脊柱单元整体角度，评估椎体成形对胸腰椎骨折三维稳定性的影响。
胸腰椎压缩性骨折手术治疗后椎体复位后会形成空心椎，增加内固定断裂的危险，远期椎体高度的丢失，后突畸形，引起顽固性腰背痛。由于伤椎内植骨的随访结果并不愈合，有学者尝试伤椎用骨水泥椎体成形，试图减少内固定应力，避免椎体塌陷。本研究在临床针对胸腰椎爆裂性骨折患者在椎弓根内固定的基础上，采用羟基磷灰石／聚甲基丙烯酸甲酯(HA／PMMA)骨水泥进行椎体内灌注，重建了椎体高度、强度、刚度、脊柱矢状位序列，并进行临床评估。
第一部分H刀pMMA活性骨水泥椎体成形的生物力学研究
目的:
1.评估添加不同含量的队后P珊认刚度和强度变化，以及凝固时间对
力学特性影响。
2.评估10%HA/P呱从椎体成形对老年椎体标本终板应力分布的影响。
3.评估10%HA/P呱从填塞式(Tamp)椎体成形，即在骨水泥粘度较大
时直接经椎弓根通道捣塞到椎体内，与常规注射式(Injection)椎体成
形比较，测试的压缩力和刚度变化。
4.评估颈椎在10%HA/P呱认骨水泥椎体成形后强度和刚度的变化。
5.评估10%HA/P呱认在胸腰椎骨折后椎体成形对恢复脊柱三维稳定
性的作用。
方法:
1.将纯PMMA组、10%HA/P MMA(WT)组、20%HA/P MMA(盯)组、CPC
组等四组材料，分别制成直径gllun，高10llnn的圆柱状，聚合后1小时、24
小时压缩试验，0.5。/min，压缩Zllnn，测量强度和刚度。
2.四具新鲜骨质疏松胸腰段脊柱标本(T12~L4)。X线排除腰椎骨折
或肿瘤，测量骨密度。分离后仅剩椎体和终板，随机分成对照组和椎体
成形组。在终板中心，按顺时钟座标方向，距离边缘皮质骨7咖，取9个
点，用直径2.3Inln的半球形压头以0.03nun/s的速度，下压3Inln。力与位
移曲线可计算出最大压缩力及刚度。比较终板不同位点的最大压缩力及
刚度分布差异。两组内椎体终板在相同点最大压缩力及刚度进行比较。
3.四具新鲜骨质疏松胸腰段脊柱标本(Tll~L4)。经正侧位X线排
除骨折或肿瘤，选16个椎体节段，测量骨密度。分离后仅剩下椎体和终
板，随机分成注射式成形组(Inje。t ion)和填塞式椎体成形组(Tamp)。
Slnln/min压缩6毫米或载荷一变形曲线出现了最高点，10Hz频率记录。10
%HA/PMMA行椎体成形。Injection组:经椎弓根11G的骨穿针，注射。
Tamp组:用6Inlll钻头通过椎弓根，插入5.Slnm导入棒，上下撬拨，骨水
泥为橡皮泥样，用导入棒将骨水泥塞入到椎体中。初始和处理后2小时
分别压缩。计算最大压缩力和刚度。可重复测量的方差分析处理数据。
4.三具新成年男性颈椎标本(C4一6C)，选择9个椎体节段，骨密度测
一3一
量正常。分离仅剩下椎体和终板，以Slnln/min压缩4毫米或椎体的负载
压力出现下降。10%HA/P呱认骨水泥自前椎体正中用11G的骨穿针，进
入约1一1.scm，注射2一3ml。固化2小时后再压缩。计算在位移3llnn时
的压缩力、最大压缩力、最大压缩力的位移和刚度。
5.七具新鲜胸腰段脊柱标本(T12~L5)，用聚甲基丙烯酸甲酷平行包
埋标本的两端，在三位运动试验机上测试标本的前屈、后伸、左侧弯、右
侧弯、左旋转、右旋转，加载0一SNM，用三维显微激光扫描仪采集图象。
测量正常、骨折后、伤椎椎体成形后、疲劳测试后的中性区和运动范围。
骨折模型制备:在Ll椎体前中间用3llun的钻头，深度Icm，在MTS试验
机上屈曲12度，在1秒内压缩力迅速提升到10KN，至椎体骨折。10%
队/P枷A骨水泥经双侧椎弓根每侧灌注4ml，共8~9毫升，固化2小时
后测试。疲劳测试:屈曲12度，屈曲加载SNm，扭转加载SNm，频率0.SHz，
疲劳3000次循环。采用重复测量方差分析，LSN方法两两比较。
结果:
1.在P枷A中添加10%HA组强度减少9.14%，刚度减少了10.17%，
20%HA组强度减少38.26%，刚度减少了48.82%，CPC骨水泥的强度只有纯
PMMA的6.92%，刚度只有10.84%。前三组1小时和24小时聚合后比较无差
别。
2.椎体终板的测试显示两组的骨密度近似，无显著性差异。最大压
缩力时的位移，正常组对照组1.33士0.44llnn，在椎体成形组 1.51士0.48llun，
组内各位点无明显差别，两组间无差
1. To determine whether the incorporation of HA in a PMMA matrix would enhance the effect of mechanical as compared to PMMA and CPC.
2.To determine the effect of endplate on the distribution structural properties with 10%HA/PMMA vertrbroplasty.
3.To compare the biomechanical properties of isolated, fractured osteoporotic vertebral bodies treated by tamp vertebroplasty or injection vertebroplasty.
4.To determine the strength and stiffness of cervical vertebral bodies subjected to compression fractures and subsequently stabilized via anterior injection of 10% HA/PMMA cement.
5.PMMA has long been in the stabilization and reconstruction of traumatic and pathological fracture of the spine. And now 10%HA/PMMA, an osteoconductive, biocompatible cement, has use as an alternative to PMMA. In this study is to determine the stabilizing effects of 10%HA/PM MA in an experimental compression fraction of Lumbar.
Methods.
1. PMMA circular cylinder, diameter 10mm and height 9mm,with 0, 10 and 20 % HA, were compressed in a materials test machine to dermine strength and stiffness in one or 24 hour.
2.The bony endplates of four intact human osteoporotic disintegrating vertebrae (T12-L5) were tested. Indentation tests were performed at
-9-
standardized test on the endplate of both contrast normal group and vertebriplasty with 10%HA/PMMA by using a 2.3-mm diameter, hemispherical indenter with a test rate of 0.2 mm/s to a depth of 3 mm. The failure load and stiffness at each site were determined from the load-displacement curves. Repeated measures analyses were used to analyze the resulting data for variation in the anterior-posterior and lateral directions, as well as to determine the effect of vertebroplasty.
3.Compression fractures were experimentally created in 4 osteoporotic VBs assigned to either the tamp or vertebroplasty group. The tamp treatment consisted of inserting 6mm drill into pedicle of vertebral body. A diameter 5mm stick raised the endplate, and filling the void with 10%HA/PMMA cement bone .The vertebroplasty treatment consisted of directly injecting 10%HA/PMMA cement into the vertebral body. The repaired vertebral bodies were recompressed to determine post treatment strength and stiffness values.
4.Three vertebral bodies (C4-C6) from three fresh spines harvested from adult male cadavers, were disarticulated, and compressed in a materials testing machine to determine initial strength and stiffness. The fractures then were repaired using an anterior injection of 10%HA/PMMA and recrushed to determine post treatment strength and stiffness values.
5.Seven T11-L5 cadaveric spinal specimens were mounted individually on test fram. The cubes were placed on the vertebra by a pin. Motion was tracked by 3D digital microscopic laser in response to applied loads of 0 to 8 Nm. The compressive impact technique was used to induce a reproducible compression fracture of L-l after partially coring out the vertebra. Load testing was performed on the intact spine. Postfracture, after bipedicular transpedicular vertebroplasty with 8 ml of 10%HA/PMMA and after flexion-extension fatiguing to 3000 cycles at 5 Nm. Ranges of motion and neutral zones were measured.
Results.
1. The addition of 10% wt and 20 % HA caused a signigcant decrease in
-1
0-
strength about 9.14% and 40%, in stiffness 10.17% and 48.82%. There is no difference between 1 hour and 24 hour. CPC cement strength is only 6.92% of PMMA alone.
2.For the contrast group endplates, both the failure load and stiffness varied significantly across the endplate surfaces, without the poster lateral regions being stronger and stiffer than other except the central regions. The central regions are lowest. On vertebroplatsty endplate, the mean failure load and stiffness increased significantly with the posterolateral regions being weaker and lower than others. The central regions are strongest.
3.Both treatments resulted in significantly stronger vertebral bodies relative to their initial state. The vertebroplasty treatment restored vertebral body stiffness to initial values
引文
1. Lautenschlager EP, Stupp SI, Keller JC.Structure and properties of acrylic bone cement.In: Ducheyne P, Hastings GW, editors.Functional behaviour of orthopaedic biomaterials.USA: Franklin Books, 1984.p.87-117.
2. Downes S, Kayser MV, Blunn G, Ali SY.An electron microscopal study of the interaction of bone with growth hormone loaded bone cement.Cells Mater 1991;1:171-6.
3. Amstutz HC, Gruen T.Clinical application of polymethylmethacrylate for total joint replacement.In: Ahstrom JP, editor.Current practice of orthopaedic surgery.St. Louis: CV Mosby Company, 1973.p. 158-82.
4. Vasquez B, Elvim C, Levenfeld B, et al.Applicatio n of tertiary amines with reduced toxicity to the curing process of acrylic bone cements.J Biomed Mater Res 1997;34:129-36.
5. Oonishi H.Mecha nical and chemical bonding of arti.cial joints.Clin Mater 1990;5:217-33.
6. Gomez-Barrena E, Chang JD, Rimnac CM, Salvati EA.The role of polyethylene properties in osteolysis after total HIP replacement.Insruet Course Lect 1996;45:187-97.
7. Dowries S.Methods of improving drug release from poly(methylmethaerylate)bone cement.Clin Mater 1991;7:227-31.
8. Working Party of the Institute of Materials.Materials Technology Foresight in Biomaterials.Institute of Materials, 1995.
9. Guan JL, Chen HC.Signal transduction in celt-matrix interactions.Int Rev Cytol 1996;168:82-121.
10. Dalby MJ, Di Silvio L, Harper EJ, Bonfield W Increasing hydroxyapatite incorporation into poly(methylmethacrylate) cement increases osteoblast adhesion and response. Biomaterials. 2002 Jan;23(2):569-76.
11. Moursi AM, Winnard AV, Winnard PL, Lannutti JJ, Seghi RR. Enhanced osteoblast response to a polymethylmethacrylate-hydroxyapatite composite. Biornaterials. 2002 Jan;23(1):133-44.
12. Heymann D,Pradal G, Benahmed M. Cellular mechanisms of calcium phosphate ceramic degradation. Histol Histopathol 1999; 14:871-7.
13. Radin S,Ducheyne P,Berthold P,Decker S. E.ect of serum proteins and osteoblasts on the surface transformation of a calcium phosphate coating: a physicochemical and Itrastructural study. J Biomed Mater Res 1998;39:234-43.
14. Jager M, Wilke A. Comprehensive biocompatibility testing of a new PMMA-hA bone cement versus conventional PMMA cement in vitro. J Biomater Sci Polym Ed. 2003;14(11):1283-98.
15. Zarnbonin G, Colucci S, Cantatore F, Grano M. Response of human osteoblasts to polymethylmetacrylate in vitro. Calcif Tissue Int 1998;62:362-5.
16. Bonfeld W, Grynpas MD,Tully AE,Bowman J,Abram J. Hydroxyapatite reinforced polyethylene a mechanically compatible implant material for bone replacement. Biomaterials 1981;2:185-6.
17. Lee R, Ogiso M,Watanab e A,Ishihara K. Examination of hydroxyapatite.lled 4-META/MMA-TBB adhesive bone cement in vitro and in vivo environment. J Biomed Mater Res 1997;38:11-6.
18. Kwon SW,Kim YS, Woo YK, Kim SS,Park JB. Hydroxyapatite impregnated bone cement: in vitro and in vivo studies. Bio-med Mater Eng 1997;7:129-40.
19. Shinzato S,Kobayashi M,Mousa WF,Kamimura M,Neo M,Kitamura Y, Kokubo T,Nakamura T. Bioaetive polymethyl methacrylate-based bone cement: comparison of glass beads,apatite-and wollastonite-contalning glass-ceramic,and hydroxyapatite.llers on mechanical and biological properties.J Biomed Mater Res 2000;51:258-72.
20. Harper EJ.Bioact ire bone cements. Proe Instn Meeh Engrs 1998;212:113 -20.
21. Perek J, Pilliar RM.Fracture toughness of composite acrylic bone cement.J Mater Sci: Mater Med 1992;3:334.
22. Vallo CI, Montemartini MA, Fanovich MA, Porto Lopez JM,Caudrado TR.Po lymethylmethacrylate based bone cement modified with hydroxyapatite.J Biomed Mater Res 1999;48:150-8.
23. Harper EJ, Cauich-Rodriguez J, Dingeldein E, Bon.eld W.Mechanical charactefisation of optimised PMMA based boneeement with HA reinforcement.European Report Bibochem, 1997.
24. Vallo CI, Montemartini PE, Fanovich MA, Porto Lopez JM, Cuadrado TR. Polymethylmethacrylate-based bone cement modified with hydroxyapatite. J Biomed Mater Res. 1999;48(2):150-8.
25. Castaldini A, Cavallini A. Setting properties of bone cement with added synthetic hydroxyapatite. Biomaterials 1985;6:55-60.
2. Downes S, Kayser MV, Blunn G, Ali SY.An electron microscopal study of the interaction of bone with growth hormone loaded bone cement.Cells Mater 1991;1:171-6.
3. Amstutz HC, Gruen T.Clinical application of polymethylmethacrylate for total joint replacement.In: Ahstrom JP, editor.Current practice of orthopaedic surgery.St. Louis: CV Mosby Company, 1973.p. 158-82.
4. Vasquez B, Elvim C, Levenfeld B, et al.Applicatio n of tertiary amines with reduced toxicity to the curing process of acrylic bone cements.J Biomed Mater Res 1997;34:129-36.
5. Oonishi H.Mecha nical and chemical bonding of arti.cial joints.Clin Mater 1990;5:217-33.
6. Gomez-Barrena E, Chang JD, Rimnac CM, Salvati EA.The role of polyethylene properties in osteolysis after total HIP replacement.Insruet Course Lect 1996;45:187-97.
7. Dowries S.Methods of improving drug release from poly(methylmethaerylate)bone cement.Clin Mater 1991;7:227-31.
8. Working Party of the Institute of Materials.Materials Technology Foresight in Biomaterials.Institute of Materials, 1995.
9. Guan JL, Chen HC.Signal transduction in celt-matrix interactions.Int Rev Cytol 1996;168:82-121.
10. Dalby MJ, Di Silvio L, Harper EJ, Bonfield W Increasing hydroxyapatite incorporation into poly(methylmethacrylate) cement increases osteoblast adhesion and response. Biomaterials. 2002 Jan;23(2):569-76.
11. Moursi AM, Winnard AV, Winnard PL, Lannutti JJ, Seghi RR. Enhanced osteoblast response to a polymethylmethacrylate-hydroxyapatite composite. Biornaterials. 2002 Jan;23(1):133-44.
12. Heymann D,Pradal G, Benahmed M. Cellular mechanisms of calcium phosphate ceramic degradation. Histol Histopathol 1999; 14:871-7.
13. Radin S,Ducheyne P,Berthold P,Decker S. E.ect of serum proteins and osteoblasts on the surface transformation of a calcium phosphate coating: a physicochemical and Itrastructural study. J Biomed Mater Res 1998;39:234-43.
14. Jager M, Wilke A. Comprehensive biocompatibility testing of a new PMMA-hA bone cement versus conventional PMMA cement in vitro. J Biomater Sci Polym Ed. 2003;14(11):1283-98.
15. Zarnbonin G, Colucci S, Cantatore F, Grano M. Response of human osteoblasts to polymethylmetacrylate in vitro. Calcif Tissue Int 1998;62:362-5.
16. Bonfeld W, Grynpas MD,Tully AE,Bowman J,Abram J. Hydroxyapatite reinforced polyethylene a mechanically compatible implant material for bone replacement. Biomaterials 1981;2:185-6.
17. Lee R, Ogiso M,Watanab e A,Ishihara K. Examination of hydroxyapatite.lled 4-META/MMA-TBB adhesive bone cement in vitro and in vivo environment. J Biomed Mater Res 1997;38:11-6.
18. Kwon SW,Kim YS, Woo YK, Kim SS,Park JB. Hydroxyapatite impregnated bone cement: in vitro and in vivo studies. Bio-med Mater Eng 1997;7:129-40.
19. Shinzato S,Kobayashi M,Mousa WF,Kamimura M,Neo M,Kitamura Y, Kokubo T,Nakamura T. Bioaetive polymethyl methacrylate-based bone cement: comparison of glass beads,apatite-and wollastonite-contalning glass-ceramic,and hydroxyapatite.llers on mechanical and biological properties.J Biomed Mater Res 2000;51:258-72.
20. Harper EJ.Bioact ire bone cements. Proe Instn Meeh Engrs 1998;212:113 -20.
21. Perek J, Pilliar RM.Fracture toughness of composite acrylic bone cement.J Mater Sci: Mater Med 1992;3:334.
22. Vallo CI, Montemartini MA, Fanovich MA, Porto Lopez JM,Caudrado TR.Po lymethylmethacrylate based bone cement modified with hydroxyapatite.J Biomed Mater Res 1999;48:150-8.
23. Harper EJ, Cauich-Rodriguez J, Dingeldein E, Bon.eld W.Mechanical charactefisation of optimised PMMA based boneeement with HA reinforcement.European Report Bibochem, 1997.
24. Vallo CI, Montemartini PE, Fanovich MA, Porto Lopez JM, Cuadrado TR. Polymethylmethacrylate-based bone cement modified with hydroxyapatite. J Biomed Mater Res. 1999;48(2):150-8.
25. Castaldini A, Cavallini A. Setting properties of bone cement with added synthetic hydroxyapatite. Biomaterials 1985;6:55-60.