矿化骨胶原结合锶复合骨水泥生物活性及生物力学测定
发布时间：2019-01-16 06:00
【摘要】：背景：在关节置换术中,骨水泥通过与周围骨组织形成稳定的机械性结合,可以实现相对长期固定,但随着时间延长,骨-骨水泥界面会出现松动,因此研发具有生物活性的骨水泥具有显著临床意义。本课题组之前研究发现,在聚甲基丙烯酸甲酯中添加15%的矿化骨胶原(Mineralized collagen, MC),可以提高骨水泥的生物活性。目的：为了进一步提高生物活性,本文主要是通过混合磷酸氢锶(SrHPO4)、矿化骨胶原及聚甲基丙烯酸甲酯(Polymethylmethacrylate, PMMA)制备了一种新型生物活性骨水泥(SR-MC-PMMA),研究新型生物活性骨水泥的生物力学特性及骨组织相容性。方法：将SrHPO4按不同比例(1%、2%、5%、10%)添加到含有矿化骨胶原MC 15%的聚甲基丙烯酸甲酯PMMA复合骨水泥中,按照外科植入物丙烯酸类树脂骨水泥国家标准ISO 5833,检测生物力学性能,包括凝固时间、抗压强度及抗弯曲强度。在SrHPO4、MC与PMMA比例分别为5%、15%的条件下,制取SR-MC-PMMA生物活性骨水泥,试验选用的是GB/T 16886.5-2013/ISO 10993-5:1999推荐的L-929小鼠成纤维细胞对含5%的SrHPO4的SR-MC-PMMA骨水泥、MC-PMMA骨水泥、C-PMMA骨水泥的浸提液进行细胞毒性检查.按照国家标准GB/T 16886-2003/ISO 10993-5:1999规定的体外细胞毒性分级法标准,检测生物活性骨水泥的体外细胞毒性。将SR-MC-PMMA在无菌条件下,包埋于成熟的新西兰家兔股骨内侧髁,分别于术后4周、8周、12周取出家兔的股骨,经固定液固定后,行Micro-CT和硬组织切片,观察指定区域骨CT密度及骨组织相容性。通过Image-Pro18.0软件,测量分析新生骨组织在植入骨水泥材料中的面积比,进行分析。结果：在含有15%矿化骨胶原的聚甲基丙烯酸甲酯骨水泥中,添加5%的SrHPO4,抗压强度为(73.77±6.33MPa),压缩模量为(1.74±0.11GPa),符合骨水泥国家标准(ISO5833和ASTM F451标准)抗压强度不低于70MPa。凝固特性表明添加了5% SrHPO4的之后的,改性骨水泥操作性能变化不大,具有较好的操作性能。按照GB/T 16886／ISO10993检测SR-MC-PMMA骨水泥的生物安全性,包括体外细胞毒性,急性全身毒性反应,慢性肝肾毒性实验,试验中均无毒性反应。在兔股骨标本组织切片观察发现,在试验第4周、8周、12周,SR-MC-PMMA组均表现出较好的骨组织长入,在第12周,SR-MC-PMMA组为(15.99±0.41%)与MC-PMMA组(9.85±0.72%)相比具有差异。在PMMA组中,第4周、8周、12周,骨组织长入比例无明显差异。MC-PMMA、 SR-MC-PMMA组中,相比于第4周,第8周和第12周,均有新生骨组织长入,具有统计学差异。结论：在含有15%矿化骨胶原的聚甲基丙烯酸甲酯骨水泥基础上,添加5%的SrHPO4后抗压强度,抗弯曲强度及凝固性能,均符合ISO 5833生物材料标准。SR-MC-PMMA骨水泥在体外细胞实验和体内急性全身反应、慢性肝肾毒性试验中,表现较好的生物安全性。在兔骨组织包埋中,相比于C-PMMA、MC-PMMA骨水泥,SR-MC-PMMA骨水泥表现出有更多新生骨组织长入,具有较好的生物活性。
[Abstract]:Background: during joint replacement, bone cement can be fixed relatively for a long time by forming a stable mechanical combination with the surrounding bone tissue. However, as time goes on, the interface between bone and bone cement will be loosened. Therefore, it is of great clinical significance to develop bone cement with biological activity. Our previous study found that adding 15% mineralized collagen (Mineralized collagen, MC), to polymethyl methacrylate can improve the biological activity of bone cement. Objective: to further improve biological activity, a new bioactive bone cement (SR-MC-PMMA) was prepared by mixing strontium hydrogen phosphate (SrHPO4), mineralized bone collagen and polymethyl methacrylate (Polymethylmethacrylate, PMMA). The biomechanical properties and bone histocompatibility of new bioactive bone cement were studied. Methods: SrHPO4 was added to polymethyl methacrylate (PMMA) composite bone cement containing 15% MC of mineralized bone collagen according to the national standard of acrylic resin bone cement (ISO 5833). Test biomechanical properties, including solidification time, compressive strength and bending strength. Under the condition that the ratio of SrHPO4,MC to PMMA is 5% and 15% respectively, the bioactive SR-MC-PMMA bone cement was prepared. In the experiment, L-929 mouse fibroblasts recommended by GB/T 16886.5-2013/ISO 10993-5: 1999 were used to test the cytotoxicity of SR-MC-PMMA bone cement, MC-PMMA bone cement and C-PMMA bone cement extract containing 5% SrHPO4. The in vitro cytotoxicity of bioactive bone cement was detected according to the standard of in vitro cytotoxicity classification set by GB/T 16886-2003/ISO 10993-5: 1999. SR-MC-PMMA was embedded in the medial femoral condyle of mature New Zealand rabbits in aseptic condition. The femur was removed at 4 weeks, 8 weeks and 12 weeks after operation. After fixed with fixed solution, Micro-CT and hard tissue sections were performed. Bone CT density and bone histocompatibility were observed. The area ratio of new bone tissue in bone cement implant was measured and analyzed by Image-Pro18.0 software. Results: the compressive strength and compression modulus of SrHPO4, were (73.77 卤6.33MPa) and (1.74 卤0.11GPa), respectively. Meet the national standards of bone cement (ISO5833 and ASTM F451) compressive strength is not less than 70 MPA. The solidification characteristics showed that the modified bone cement with 5% SrHPO4 had little change in operating performance and had better performance. The biological safety of SR-MC-PMMA bone cement was detected according to GB/T 16886/ISO10993, including in vitro cytotoxicity, acute systemic toxicity, chronic hepatorenal toxicity test, and no toxic reaction in the test. At the 4th week, 8th week, 12th week, the SR-MC-PMMA group showed good bone tissue growth, and at the 12th week. There was significant difference between SR-MC-PMMA group (15.99 卤0.41%) and MC-PMMA group (9.85 卤0.72%). In the PMMA group, there was no significant difference in the proportion of bone tissue growth in the 4th, 8th, 12th week, but in the MC-PMMA, SR-MC-PMMA group, there was significant difference between the 4th, 8th and 12th week. Conclusion: on the basis of polymethyl methacrylate bone cement containing 15% mineralized bone collagen, the compressive strength, bending strength and solidification property of 5% SrHPO4 were added. SR-MC-PMMA bone cement showed good biological safety in vitro cell test, acute systemic reaction in vivo and chronic hepatorenal toxicity test. Compared with C-PMMA-MC-PMMA bone cement, SR-MC-PMMA bone cement showed more new bone tissue growth and better biological activity.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R687;R318.08
本文编号：2409535
[Abstract]:Background: during joint replacement, bone cement can be fixed relatively for a long time by forming a stable mechanical combination with the surrounding bone tissue. However, as time goes on, the interface between bone and bone cement will be loosened. Therefore, it is of great clinical significance to develop bone cement with biological activity. Our previous study found that adding 15% mineralized collagen (Mineralized collagen, MC), to polymethyl methacrylate can improve the biological activity of bone cement. Objective: to further improve biological activity, a new bioactive bone cement (SR-MC-PMMA) was prepared by mixing strontium hydrogen phosphate (SrHPO4), mineralized bone collagen and polymethyl methacrylate (Polymethylmethacrylate, PMMA). The biomechanical properties and bone histocompatibility of new bioactive bone cement were studied. Methods: SrHPO4 was added to polymethyl methacrylate (PMMA) composite bone cement containing 15% MC of mineralized bone collagen according to the national standard of acrylic resin bone cement (ISO 5833). Test biomechanical properties, including solidification time, compressive strength and bending strength. Under the condition that the ratio of SrHPO4,MC to PMMA is 5% and 15% respectively, the bioactive SR-MC-PMMA bone cement was prepared. In the experiment, L-929 mouse fibroblasts recommended by GB/T 16886.5-2013/ISO 10993-5: 1999 were used to test the cytotoxicity of SR-MC-PMMA bone cement, MC-PMMA bone cement and C-PMMA bone cement extract containing 5% SrHPO4. The in vitro cytotoxicity of bioactive bone cement was detected according to the standard of in vitro cytotoxicity classification set by GB/T 16886-2003/ISO 10993-5: 1999. SR-MC-PMMA was embedded in the medial femoral condyle of mature New Zealand rabbits in aseptic condition. The femur was removed at 4 weeks, 8 weeks and 12 weeks after operation. After fixed with fixed solution, Micro-CT and hard tissue sections were performed. Bone CT density and bone histocompatibility were observed. The area ratio of new bone tissue in bone cement implant was measured and analyzed by Image-Pro18.0 software. Results: the compressive strength and compression modulus of SrHPO4, were (73.77 卤6.33MPa) and (1.74 卤0.11GPa), respectively. Meet the national standards of bone cement (ISO5833 and ASTM F451) compressive strength is not less than 70 MPA. The solidification characteristics showed that the modified bone cement with 5% SrHPO4 had little change in operating performance and had better performance. The biological safety of SR-MC-PMMA bone cement was detected according to GB/T 16886/ISO10993, including in vitro cytotoxicity, acute systemic toxicity, chronic hepatorenal toxicity test, and no toxic reaction in the test. At the 4th week, 8th week, 12th week, the SR-MC-PMMA group showed good bone tissue growth, and at the 12th week. There was significant difference between SR-MC-PMMA group (15.99 卤0.41%) and MC-PMMA group (9.85 卤0.72%). In the PMMA group, there was no significant difference in the proportion of bone tissue growth in the 4th, 8th, 12th week, but in the MC-PMMA, SR-MC-PMMA group, there was significant difference between the 4th, 8th and 12th week. Conclusion: on the basis of polymethyl methacrylate bone cement containing 15% mineralized bone collagen, the compressive strength, bending strength and solidification property of 5% SrHPO4 were added. SR-MC-PMMA bone cement showed good biological safety in vitro cell test, acute systemic reaction in vivo and chronic hepatorenal toxicity test. Compared with C-PMMA-MC-PMMA bone cement, SR-MC-PMMA bone cement showed more new bone tissue growth and better biological activity.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R687;R318.08
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