新型多孔生物活性骨水泥用于椎體成型術(shù)的動(dòng)物實(shí)驗(yàn)研究
發(fā)布時(shí)間：2018-08-08 11:00
【摘要】：研究背景: 骨質(zhì)疏松癥（Osteoporosis，OP）是我國老年人群的三大疾病之一。50歲以上人群中，OP總患病率女性為20.7%，男性為14.4%。隨著年齡增加，OP的發(fā)病率急劇增加，80歲以上女性O(shè)P發(fā)病率甚至高達(dá)66%。脊柱是OP受累最為嚴(yán)重的部位，50歲以上女性的脊柱OP發(fā)病率為28%，遠(yuǎn)遠(yuǎn)高于股骨的15%。因此，骨質(zhì)疏松性椎體壓縮骨折的發(fā)生率遠(yuǎn)遠(yuǎn)高于其他部位骨折，我國每年新發(fā)椎體壓縮骨折約l81萬例，預(yù)計(jì)至2020年椎體骨折患者將高達(dá)3675萬人。椎體壓縮骨折會(huì)導(dǎo)致患者劇烈疼痛、出現(xiàn)神經(jīng)功能障礙，同時(shí)，，由于脊柱后凸畸形改變軀干力線，導(dǎo)致臨近節(jié)段椎體骨折風(fēng)險(xiǎn)增加，形成骨折-畸形-再骨折的惡性循環(huán)。所以，如何重新恢復(fù)壓縮骨折椎體的強(qiáng)度和高度，降低骨質(zhì)疏松椎體壓縮骨折發(fā)生率，使骨質(zhì)疏松的患者不再出現(xiàn)駝背畸形具有重要的臨床價(jià)值和深遠(yuǎn)的社會(huì)意義。 椎體成型術(shù)和球囊成型術(shù)是治療骨質(zhì)疏松椎體壓縮性骨折的有效手段，目前使用的椎體填充材料絕大多數(shù)是聚甲基丙烯酸甲酯（Polymethyl Methacrylate，PMMA）。然而，該材料存在明顯的缺陷：單純的力學(xué)支撐，不具有骨傳導(dǎo)、骨誘導(dǎo)作用；無法被自身組織吸收替代；彈性模量過高。因此，迫切需要一種新型的椎體成型填充材料，在對疏松椎體提供力學(xué)支撐的同時(shí)，還可通過骨傳導(dǎo)和骨誘導(dǎo)作用促進(jìn)骨折的愈合。 課題組前期將生物玻璃、殼聚糖與聚甲基丙烯酸甲酯復(fù)合，研發(fā)了一種新型可注射型多孔生物活性骨水泥，發(fā)現(xiàn)該材料具有適宜的生物力學(xué)強(qiáng)度和良好的體外生物活性，在體內(nèi)部分可吸收。但能否將其作為椎體成型術(shù)的填充材料，以及其對骨質(zhì)疏松椎體的作用及尚不明確。 研究目的: 通過兔骨質(zhì)疏松模型評估新型可注射型多孔生物活性骨水泥作為椎體成型材料的有效性和可行性。 材料方法: 將生物玻璃、聚甲基丙烯酸甲酯和殼聚糖按照4:5:1的比例構(gòu)建多孔生物活性骨水泥。骨水泥固/液比為1.5:1。首先，通過掃描電子顯微鏡觀察材料表面形態(tài)，了解材料各組份分布情況。然后，將骨水泥樣本浸泡于PBS磷酸緩沖液中降解4周，通過生物力學(xué)實(shí)驗(yàn)，檢測骨水泥的體外最大抗壓縮強(qiáng)度。同時(shí)，將骨水泥浸泡于模擬體液中，通過X線衍射分析，評價(jià)材料的體外生物活性。采用隨機(jī)對照研究方案，將80只新西蘭大白兔隨機(jī)分為去勢組（OVX, n=72）和假手術(shù)組（Sham，n=8）。通過雙側(cè)卵巢去勢法，建立兔骨質(zhì)疏松模型。采用隨機(jī)對照研究方案，將去勢組隨機(jī)分為BBC組（BBC, n=24）、PMMA組（PMMA, n=24）和骨質(zhì)疏松對照組（CON,n=24）。通過模擬椎體成形術(shù)，分別在BBC組和PMMA組兔子L4、L5椎體注射骨水泥材料，每組均于術(shù)后1周、4周、12周處死8只。采用組織學(xué)、MicroCT及生物力學(xué)實(shí)驗(yàn)評估新型多孔生物活性骨水泥對脊柱骨質(zhì)疏松的治療作用。 結(jié)果: 骨水泥材料固化后掃描電鏡結(jié)果提示：生物玻璃顆粒和殼聚糖顆粒均勻的分布于PMMA基質(zhì)當(dāng)中。體外生物力學(xué)檢測結(jié)果提示：在各時(shí)間點(diǎn)，新型材料的最大抗壓縮強(qiáng)度均小于PMMA （P0.05）。X線衍射結(jié)果顯示：在模擬體液浸泡7天后，骨水泥表面有磷灰石層形成，并且隨浸泡時(shí)間延長，磷灰石層增厚。組織形態(tài)學(xué)觀察發(fā)現(xiàn)，椎體成形術(shù)后4周，BBC組可見骨連接形成；術(shù)后12周，可見新生骨小梁。顯微CT結(jié)果顯示：椎體成型術(shù)后4周至12周，BBC組的骨體積分?jǐn)?shù)（BV/TV）從28.27±1.69%增至38.43±1.34%，而PMMA組的骨體積分?jǐn)?shù)無明顯變化。生物力學(xué)實(shí)驗(yàn)結(jié)果表明，在椎體成型術(shù)后1周、4周、12周，BBC組和PMMA組椎體的最大抗壓縮強(qiáng)度均明顯高于骨質(zhì)疏松對照組（P0.05）。術(shù)后1周、4周，BBC組椎體的最大抗壓縮強(qiáng)度均低于PMMA組（P0.05）。術(shù)后12周，兩組椎體最大抗壓縮強(qiáng)度無明顯區(qū)別。 結(jié)論: 新型多孔生物活性骨水泥在體內(nèi)可部分吸收，有一定的成骨活性，可以迅速有效地改善骨質(zhì)疏松椎體骨小梁的三維構(gòu)筑，提高椎體的力學(xué)強(qiáng)度。隨著進(jìn)一步的改性研究，有望成為新型的椎體成型材料。
[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.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R318.08
本文編號：2171585
[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.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R318.08
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