可降解镁合金内固定材料的生物相容性研究

发布时间：2018-01-02 17:27

本文关键词：可降解镁合金内固定材料的生物相容性研究　出处：《吉林大学》2013年硕士论文　论文类型：学位论文

【摘要】：研究背景：生物医用材料是医学与材料科学结合的产物，在临床工作尤其外科工作中，拥有相当重要的地位。首先，金属材料因高强度、韧性好及抗腐蚀性能好，更适用于修复和置换人体骨组织。医用金属材料应用最为广泛，主要包括钛合金、不锈钢、钴铬合金。但它们在应用中面临着一些问题，由于生理环境的腐蚀而产生的重金属离子向组织内扩散，从而对人体健康造成损害；同时由于弹性模量明显高于骨组织，造成应力遮挡，导致内固定失败或造成应力性骨折等。而且金属内固定多需要在骨折愈合后，取出内固定。对于患者来说，再次增加了经济负担。所以研发新型金属基生物植入材料是基于医学发展和人文关怀应运而生的。尤其是与人类骨骼生物性能相近，并能发挥完美的固定功能，甚至能够促进骨组织修复，加速骨组织愈合的全新材料。同时其在体内具备可降解性。镁及镁合金成为生物医学材料研究的关注焦点。与现有医用金属材料相比，镁及其合金具有明显优势。首先镁作为人体必须的营养元素，生物安全性高。镁在人体内金属离子含量位列第四位。镁的重要性显而易见。镁离子的生理功能体现在其为酶的组成部分，参与新陈代谢。其次镁能够通过泌尿系统排泄，人体摄入大量镁后，血清镁含量仍不会明显升高。再次镁与骨组织的密度及弹性模量相似，避免应力遮挡。同时镁资源丰富，是最容易获得的金属元素之一。鉴于上述优点，镁及其合金的研究成为生物材料领域重要的研究方向。但镁合金缺点同样明显，如局部腐蚀，降解行为不可控，可塑性差，力学特性差等。近年，镁与锌及钙的合金，在强度、可塑性上表面优异。但生物相容性、可控性降解仍有问题。本文中Mg-Zn-Ca-Y合金采用Ca元素，Zn元素，耐腐蚀性的稀土元素Y作为合金化元素，使用传统熔炼锻造技术，合成Mg-Zn-Ca-Y合金。本人通过溶血实验及组织相容性试验对镁合金进行生物相容性评价。为镁合金的改良提供依据。目的：本研究对新型Mg-Zn-Ca-Y合金的溶血率与浸提液浓度之间的关系及组织相容性系统评价，同时观察测量新型合金植入动物体内后，动物局部组织与全身状态的改变，分析其对机体的影响。为新型材料应用于临床做必要的试验与准备，为制成临床安全、满意的可降解合金材料提供科学依据。方法：第一部分，将镁合金浸提液制备为不同浓度：100%、75%、50%、25%、10%、5%、2.5%、1%，按照GBT16886.4-2003《医疗器械生物学评价》第4部分《与血液相互作用试验选择》的要求，进行溶血试验。第二部分，于白兔骶嵴肌内植入Mg合金短棒，观察、测量白兔植入后的情况：体重、饮食、离子、肝功、肾功水平，植入点组织局部反应，肝、肾情况。分别于术前、术后1、7、14、28、54天抽取白兔耳缘静脉血液，观察分析白兔在植入合金材料后肝功、离子、肾功是否存在变化及变化情况；利用HE染色，分别对不同时间点取出的植入物周边纤维膜厚度及炎性改变情况进行观察，分别于植入后3、6个月，利用扫描电镜，观察纤维膜厚度，以及电镜观察1周、2周、1月、3月、6月镁合金分解、腐蚀情况，对镁合金在动物体内的降解情况及对白兔的影响进行分析。结果： Mg-Zn-Ca-Y合金的浸提液在100%、75%、50%、25%、10%、5%、2.5%及1%稀释度下的溶血率分别为64.7%、62.4%、58.0%、34.2%、10.6%，4.7%，0.7%和0.2%。随着浓度的减少，Mg+浓度逐渐下降，而钠离子处于基本稳定的状态,考虑Mg+浓度是影响其体外试验溶血的主要因素之一。植入日本大耳白兔骶棘肌肌肉内，一般情况良好，，切口无红肿及分泌物。HE染色观察的结果显示，2周后纤维膜逐渐形成。12周后纤维膜变薄。镁合金样品在植入后1、2周，肉眼观察表面无明显变化，但电镜观察，其表面已出现少量裂隙。随着时间推移，4、8、12周的样品中，肉眼观察，其表面已出现腐蚀情况，电镜观察其表面腐蚀情况较前严重，部分出现较为严重的点腐蚀。电镜观察局部反应膜结果：实验组纤维膜切面厚度15.1μm，对照组11.4μm。4周后标本出现表面氧化，粗糙，肉眼未观察到产气。结论：Mg-Zn-Ca-Y合金的体外溶血性能有待提高，考虑其受分解的Mg+离子的影响。Mg-Zn-Ca-Y合金的组织相容性通过国家标准。植入后，动物离子、肝功及肝肾脏均未见明显异常。
[Abstract]:Background: biomedical materials is the combination of medicine and material science, especially in clinical surgical work, has a very important position. First of all, metal materials have high strength, good toughness and good corrosion resistance, more suitable for the repair and replacement of human bone tissue. The application of Biomedical Metal materials most widely, mainly including titanium alloy, stainless steel, cobalt chromium alloy. But they are facing some problems in the application of heavy metal ions, due to corrosion of the physiological environment of diffusion into the tissue, thereby causing damage to human health; at the same time due to the elastic modulus was significantly higher than that of bone tissue, cause stress shielding, leading to the failure of internal fixation should be or cause stress fracture. And the metal internal fixation in fracture healing, removing internal fixation. For the patients, to increase the economic burden. So the research and development of new metal basal implant materials Is the development of medicine and humanistic care. Especially came into being based on biological properties are similar to human bones, and can play a perfect fixed function, can promote bone tissue repair, accelerate newbone tissue healing. At the same time in vivo with biodegradability. Magnesium and magnesium alloy has become the focus of biomedical materials. Compared with the existing medical metal materials, magnesium alloy has obvious advantages. Firstly, magnesium as nutrient elements necessary to human body, high biological safety. The magnesium ion content in the body of magnesium was ranked fourth. The importance is obvious. The physiological function of magnesium ion in part reflected in the The new supersedes the old., as enzymes. Secondly through the urinary excretion of magnesium, magnesium intake body, serum magnesium content is still not significantly elevated again. Density and elastic modulus of magnesium and bone tissue similar to avoid stress At the same time occlusion. Magnesium is rich in resources, is one of the most readily available metal elements. In view of the above advantages, magnesium and its alloys have become an important research direction in the field of biological material. But the disadvantage is equally obvious, such as magnesium alloy, corrosion, degradation behavior is not controllable, plasticity, mechanical properties are poor. In recent years, alloy. Magnesium and zinc and calcium in strength, plasticity on the surface. But excellent biocompatibility and controllable degradation still has a problem. This paper adopts Ca Mg-Zn-Ca-Y alloy elements, Zn elements, rare earth elements Y corrosion resistance as alloying elements, the use of traditional melting forging technology of Mg-Zn-Ca-Y Alloy Synthesized by hemolysis test. I and tissue compatibility test of magnesium alloy for biocompatibility evaluation. Provide the basis for the improvement of magnesium alloy.
Objective: To study the hemolysis rate of the Mg-Zn-Ca-Y alloy and the model of relationship between leaching solution concentration and tissue compatibility evaluation system, at the same time to observe and measure the new alloy implanted in animal, animal tissue and body condition change, analyze the effects on the body. As the application of new materials to do clinical test and prepare the necessary that made the clinical safety, provide scientific basis for the satisfaction of the degradable alloy material.
Methods: in the first part, the magnesium alloy extract preparation for different concentrations: 100%, 75%, 50%, 25%, 10%, 5%, 2.5%, 1%, fourth part evaluation > < interactions with blood test requirements in accordance with the Select > GBT16886.4-2003< medical biology, hemolytic test. In the second part, the white rabbit sacral crest intramuscular implantation of Mg alloy rods, observation, measurement of white rabbits after implantation: body weight, diet, ion, liver function, renal function level, local reaction, implantation of liver, kidney. At preoperative, postoperative 1,7,14,28,54 days from rabbit ear vein blood in rabbits, to observe and analyze the alloy material after implantation liver function, renal function and ion, whether there are changes and changes; using HE staining, the thickness of fibrous membrane around the implant and inflammation at different time points out changes were observed respectively in 3,6 months after implantation, using scanning electron microscope, to observe the thickness of fibrous membrane, And the electron microscope observation of 1 weeks, 2 weeks, January, March, June, magnesium alloy decomposition, corrosion, analysis of magnesium alloy in the degradation of animal body and influence on rabbits. Results: the extracts in 100%, 75%, 50%, 25%, 10%, 5%, 2.5% and 1% of Mg-Zn-Ca-Y alloy, hemolytic dilution the degree of the rate were 64.7%, 62.4%, 58%, 34.2%, 10.6%, 4.7%, 0.7% and 0.2%. with the concentration decreased, the concentration of Mg+ decreased gradually, while the sodium ion in stable state, consider the concentration of Mg+ is one of the main factors affecting the haemolysis test in vitro. Implantation of Japanese white rabbits in the sacral spine muscle generally, in good condition, no incision swelling and secretion of.HE staining showed that the fibrous membrane gradually formed after 2 weeks.12 weeks after the fiber membrane thinning. Magnesium alloy samples at 1,2 weeks after implantation, observed no obvious change on the surface, but the electron microscope, the surface has small cracks. With time Time, visual observation to 4,8,12 weeks in the sample, the surface has been corrosion, electron microscope observation of the surface corrosion was serious, some of the more severe corrosion. Local reaction membrane electron microscope results: the experimental group fiber membrane slice thickness of 15.1 m, the control group 11.4 m.4 weeks after the specimen surface oxidation, rough, naked eye was not observed in the gas production.
Conclusion: the in vitro hemolytic properties of Mg-Zn-Ca-Y alloy should be improved, considering the Mg+ ion decomposition effect of.Mg-Zn-Ca-Y alloy biocompatibility by national standards. After implantation, animal ion, liver function and liver and kidney showed no obvious abnormalities.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R318.08

【参考文献】