新型多孔生物活性骨水泥用于椎体成型术的动物实验研究

发布时间：2018-08-08 11:00

【摘要】：研究背景: 骨质疏松症（Osteoporosis，OP）是我国老年人群的三大疾病之一。50岁以上人群中，OP总患病率女性为20.7%，男性为14.4%。随着年龄增加，OP的发病率急剧增加，80岁以上女性OP发病率甚至高达66%。脊柱是OP受累最为严重的部位，50岁以上女性的脊柱OP发病率为28%，远远高于股骨的15%。因此，骨质疏松性椎体压缩骨折的发生率远远高于其他部位骨折，我国每年新发椎体压缩骨折约l81万例，预计至2020年椎体骨折患者将高达3675万人。椎体压缩骨折会导致患者剧烈疼痛、出现神经功能障碍，同时，，由于脊柱后凸畸形改变躯干力线，导致临近节段椎体骨折风险增加，形成骨折-畸形-再骨折的恶性循环。所以，如何重新恢复压缩骨折椎体的强度和高度，降低骨质疏松椎体压缩骨折发生率，使骨质疏松的患者不再出现驼背畸形具有重要的临床价值和深远的社会意义。椎体成型术和球囊成型术是治疗骨质疏松椎体压缩性骨折的有效手段，目前使用的椎体填充材料绝大多数是聚甲基丙烯酸甲酯（Polymethyl Methacrylate，PMMA）。然而，该材料存在明显的缺陷：单纯的力学支撑，不具有骨传导、骨诱导作用；无法被自身组织吸收替代；弹性模量过高。因此，迫切需要一种新型的椎体成型填充材料，在对疏松椎体提供力学支撑的同时，还可通过骨传导和骨诱导作用促进骨折的愈合。课题组前期将生物玻璃、壳聚糖与聚甲基丙烯酸甲酯复合，研发了一种新型可注射型多孔生物活性骨水泥，发现该材料具有适宜的生物力学强度和良好的体外生物活性，在体内部分可吸收。但能否将其作为椎体成型术的填充材料，以及其对骨质疏松椎体的作用及尚不明确。研究目的: 通过兔骨质疏松模型评估新型可注射型多孔生物活性骨水泥作为椎体成型材料的有效性和可行性。材料方法: 将生物玻璃、聚甲基丙烯酸甲酯和壳聚糖按照4:5:1的比例构建多孔生物活性骨水泥。骨水泥固/液比为1.5:1。首先，通过扫描电子显微镜观察材料表面形态，了解材料各组份分布情况。然后，将骨水泥样本浸泡于PBS磷酸缓冲液中降解4周，通过生物力学实验，检测骨水泥的体外最大抗压缩强度。同时，将骨水泥浸泡于模拟体液中，通过X线衍射分析，评价材料的体外生物活性。采用随机对照研究方案，将80只新西兰大白兔随机分为去势组（OVX, n=72）和假手术组（Sham，n=8）。通过双侧卵巢去势法，建立兔骨质疏松模型。采用随机对照研究方案，将去势组随机分为BBC组（BBC, n=24）、PMMA组（PMMA, n=24）和骨质疏松对照组（CON,n=24）。通过模拟椎体成形术，分别在BBC组和PMMA组兔子L4、L5椎体注射骨水泥材料，每组均于术后1周、4周、12周处死8只。采用组织学、MicroCT及生物力学实验评估新型多孔生物活性骨水泥对脊柱骨质疏松的治疗作用。结果: 骨水泥材料固化后扫描电镜结果提示：生物玻璃颗粒和壳聚糖颗粒均匀的分布于PMMA基质当中。体外生物力学检测结果提示：在各时间点，新型材料的最大抗压缩强度均小于PMMA （P0.05）。X线衍射结果显示：在模拟体液浸泡7天后，骨水泥表面有磷灰石层形成，并且随浸泡时间延长，磷灰石层增厚。组织形态学观察发现，椎体成形术后4周，BBC组可见骨连接形成；术后12周，可见新生骨小梁。显微CT结果显示：椎体成型术后4周至12周，BBC组的骨体积分数（BV/TV）从28.27±1.69%增至38.43±1.34%，而PMMA组的骨体积分数无明显变化。生物力学实验结果表明，在椎体成型术后1周、4周、12周，BBC组和PMMA组椎体的最大抗压缩强度均明显高于骨质疏松对照组（P0.05）。术后1周、4周，BBC组椎体的最大抗压缩强度均低于PMMA组（P0.05）。术后12周，两组椎体最大抗压缩强度无明显区别。结论: 新型多孔生物活性骨水泥在体内可部分吸收，有一定的成骨活性，可以迅速有效地改善骨质疏松椎体骨小梁的三维构筑，提高椎体的力学强度。随着进一步的改性研究，有望成为新型的椎体成型材料。
[Abstract]:Research background:
Osteoporosis (OP) is one of the three major diseases in the elderly population of our country. Among the people over.50 years old, the total prevalence rate of OP is 20.7%. As the male is 14.4%., the incidence of OP increases sharply with the age of 14.4%.. The incidence of OP in women over 80 years old is even higher than that of 66%. spine, the most serious part of OP involvement, the OP of the spinal OP for women over 50 years old. The incidence of the disease is 28%, far higher than the 15%. of the femur, so the incidence of osteoporotic vertebral compression fracture is far higher than that of other parts. In China, there are about l81 ten thousand new vertebral compression fractures in China each year. It is expected that the vertebral fracture patients will be up to 36 million 750 thousand in 2020. At the same time, the spinal kyphosis changes the trunk line, resulting in an increase in the risk of fracture of the adjacent vertebral body and the formation of a vicious cycle of fracture malformation and refracture. So, how to restore the strength and height of the compressed vertebral body, reduce the incidence of osteoporotic vertebral compression fractures, and make the patients with osteoporosis no longer a humpback deformity It has important clinical value and profound social significance.
Vertebroplasty and balloon angioplasty are effective methods for the treatment of osteoporotic vertebral compression fractures. Most of the materials used now are Polymethyl Methacrylate (PMMA). However, there are obvious defects in this material: simple mechanical support, no bone conduction, bone induction; A new type of vertebroplasty filling material is urgently needed, which can promote the healing of fracture by bone conduction and bone induction, as well as a new type of vertebroplasty filling material.
A new type of injectable porous bioactive bone cement was developed by combining bioactive bioactive bone cement with chitosan and polymethyl methacrylate. It was found that the material has a suitable biomechanical strength and good bioactivity in vitro, which can be absorbed in the body, but it can be used as a filling material for vertebroplasty. Its effect on osteoporotic vertebral body is not clear.
The purpose of the study is:
The validity and feasibility of a new injectable porous bioactive bone cement as a vertebral molding material were evaluated by rabbit osteoporosis model.
Material methods:
Bioglass, polymethyl methacrylate and chitosan were used to construct porous bioactive bone cement in proportion to 4:5:1. The solid / liquid ratio of bone cement was 1.5:1. first. The surface morphology of the material was observed by scanning electron microscope, and the distribution of all components of the material was understood. Then, the bone cement samples were soaked in PBS phosphate buffer for 4 weeks and passed. Biomechanical experiments were conducted to detect the maximum compressive strength of bone cement in vitro. At the same time, bone cement was soaked in simulated body fluid to evaluate the biological activity of the material by X-ray diffraction analysis. 80 New Zealand white rabbits were randomly divided into OVX (n=72) and sham operation group (Sham, n=8). The castration method was used to establish a rabbit model of osteoporosis. The randomized controlled study was used to randomly divide the castration group into BBC group (BBC, n=24), group PMMA (PMMA, n=24) and osteoporosis control group (CON, n=24). By simulated vertebroplasty, the bone cement was injected into the BBC group and PMMA group, and the L5 vertebral body was injected into the L5 vertebral body respectively. Each group died at 1 weeks, 4 weeks, and 12 weeks. Only. Histological, microCT and biomechanical experiments were used to evaluate the therapeutic effect of new porous bioactive bone cement on spinal osteoporosis.
Result:
The results of scanning electron microscope after the curing of bone cement showed that the Bioglass and chitosan particles were evenly distributed in the PMMA matrix. The results of biomechanical detection in vitro showed that the maximum compressive strength of the new material was less than PMMA (P0.05) at all time points. The X-ray diffraction results showed that the bone cement was soaked in the simulated body fluid for 7 days. The surface was formed in the phosphorous limestone layer and thickened with the soaking time. Histomorphological observation showed that 4 weeks after vertebroplasty, the bone connections were formed in group BBC, and the new bone trabecula was seen at 12 weeks after the operation. The microscopic CT results showed that the bone volume fraction (BV/TV) in group BBC increased from 28.27 + 1.69% to 38. after vertebroplasty. The bone volume fraction of the PMMA group was 43 + 1.34%, and the biomechanical results showed that the maximum compressive strength of the vertebral body in group BBC and group PMMA was significantly higher than that of the control group (P0.05) at 1 weeks, 4 weeks and 12 weeks after vertebroplasty. The maximum compressive strength of the vertebral body in group BBC was lower than that of the PMMA group (P0.05) after the operation (P0.05). 12 weeks after the operation. There was no significant difference in the maximum compressive strength of the two groups.
Conclusion:
The new porous bioactive bone cement can be partially absorbed in the body and has a certain osteogenic activity. It can effectively improve the three-dimensional structure of the bone trabecular bone of the osteoporotic vertebral body and improve the mechanical strength of the vertebral body. With the further modification, it is expected to be a new type of vertebroplasty material.
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R318.08

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