兰州大学机构库 >第二临床医学院
4D打印形状记忆分支血管支架的制备 及性能研究
Alternative TitlePreparation and evaluation of 4D printing shape memory branched vascular stent
顾浩
Subtype硕士
Thesis Advisor周栋
2023-05-25
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name医学硕士
Degree Discipline外科学
Keyword4D打印 4D printing 形状记忆聚合物 shape memory polymer 分支血管支架 branch vascular stent 生物相容性 biocompatibility 急性主动脉综合征 acute aortic syndromes
Abstract

血管支架是由金属材料或高分子聚合物制成的一种管状支架。在临床中,通过在狭窄闭塞段血管或血管损伤处植入血管支架,以达到恢复病变血管处正常血液流动的目的。目前血管支架被广泛应用于颅内动脉、颈动脉、冠状动脉、主动脉、肾动脉等血管疾病的腔内治疗中,并且取得了令人满意的疗效。然而,在主动脉弓部等部位,由于这些部位复杂的解剖关系及多分支结构,当这些部位发生病变(如主动脉夹层、胸主动脉瘤等)时,传统的直筒式血管支架往往难以达到满意的临床效果,因为在支架植入过程中传统的直筒式支架容易覆盖分支血管从而导致各种严重的并发症。因此,理想的血管支架应该是定制化的分支型血管支架,能够实现个性化定制并且符合复杂解剖部位的多分支生理结构。

3D打印,又被称为增材制造,是以数字模型结构为基础,通过计算机软件和数字控制系统,应用聚合物、陶瓷、金属粉末及医用生物材料等打印墨水,以自下至上、逐层打印的方式打印出以三维虚拟模型为基础所构造出的实物模型。4D打印在3D打印的基础上加入时间作为第四维度,打印出的结构可以在受到刺激时创建或改变形状。随时间变化的参数包括温度、水、光、湿度、pH等。因此,4D打印引起了越来越多研究人员的关注,被广泛用于制造功能响应型材料。 

形状记忆聚合物(shape memory polymer,SMP)又被称为刺激响应性聚合物,这一类功能材料可以感知和响应来自光学、电学、磁场、热学和化学信号等的环境条件或刺激。SMP能够在外部刺激(例如光、热、磁、电等)下从变形形状恢复到原始形状,因此这一类材料也被誉为“智能材料”。由于形状记忆聚合物出色的生物相容性、力学性能以及可变形能力,因此在血管支架,药物载体,手术器械等方面具有巨大的潜在应用价值。

在这项研究中,我们通过化学合成得到了一种聚氨酯(polyurethane, PU),之后将PU、甲基丙烯酸二甲氨基乙酯(2-Dimethylamino ethyl methacrylate,DMAEMA)和甲基丙烯酸 2-羟乙酯(2-Hydroxyethyl methacrylate, HEMA)以不同比例混合,制备出一种可应用于数字光处理(digital light processing, DLP)打印的热响应型形状记忆聚合物墨水。通过测试不同比例聚合物的转变温度、机械强度以及形状记忆性能,得出结论:以3:5:2的质量比将PU、HEMA、DMAEMA混合,所得到的聚合物其拉伸强度可达18.1MPa,形状固定率为97.3%,形状恢复率为98.7%,能够用于临床治疗。为了验证聚合物的生物相容性,我们在聚合物上接种培养了人脐静脉内皮细胞,同时在Bal/c小鼠背部进行了为期12周的皮下埋植实验,结果表明聚合物具有低细胞毒性和优异的生物相容性,而且由于DMAEMA的存在,聚合物的抗菌性得到了改善。为了验证聚合物的血液相容性,我们采用健康志愿者的新鲜血液进行了血液相容性实验,结果显示聚合物可避免血小板聚集和溶血发生。最后,通过 Blender三维建模软件设计了分支血管支架结构,通过DLP打印机打印出了一款分支血管支架。因此,基于 4D 打印的形状记忆分支血管支架有望实现主动脉夹层、腹主动脉瘤等疾病的个性化且完全血管腔内治疗。

Other Abstract

Vascular stent is a kind of tubular stent made of metal material or polymer. In clinical practice, stent implantation is used to restore the normal blood flow in the damaged vascular area through the narrow occlusive segment of blood vessels or vascular injury. At present, vascular stents have been widely used in the endovascular treatment of intracranial artery, coronary artery, carotid artery, aorta, renal artery and other vascular diseases, and achieved satisfactory results. However, in the aortic arch and other parts, due to the complex anatomical relationship and multi-branch structure of these parts, when lesions occur in these parts (such as aortic dissection, thoracic aortic aneurysm, etc.), traditional straight-tube vascular stents are often difficult to achieve satisfactory clinical effects, because branch vessels are easy to be covered in the process of stent implantation, resulting in various serious complications. Therefore, the ideal vascular stent should be customized branch vascular stent, which can realize personalized customization and conform to the multi-branch physiological structure of complex anatomical sites.

3D printing, also known as additive manufacturing, is based on digital modeling files, through computer software and numerical control system, the application of polymer, ceramic, metal powder and medical biological materials and other printing ink, from the bottom up, layer by layer to print out a three-dimensional virtual model to construct a physical model. 4D printing adds time as a fourth dimension to 3D printing, and printed structures can be created or changed shape when stimulated. Parameters that vary with time include temperature, water, light, humidity, pH, etc. Therefore, 4D printing has attracted more and more attention from researchers and is widely used to manufacture functional responsive materials.

Shape memory polymers (SMPs) are also known as stimulation-responsive polymers. This class of functional materials can sense and respond to environmental conditions or stimuli from optical, electrical, magnetomechanical, thermal and chemical signals. These materials are also known as "smart materials" because they can be restored from deformed shape to original shape under external stimuli such as light, heat, magnetism and electricity. Because of its excellent biocompatibility, mechanical properties and deformability, shape memory polymers have great potential applications in vascular stents, drug carriers, surgical instruments, etc.

In this study, a polyurethane (PU) was synthesized chemically. PU, DMAEMA and HEMA were mixed in different proportions to produce a thermoresponsive shape memory polymer ink suitable for digital light processing (DLP) printing. By testing the transition temperature, mechanical strength and shape memory properties of polymers at different ratios, it is concluded that the polymer obtained by mixing PU, DMAEMA and HEMA at a mass ratio of 3:5:2 has tensile strength up to 18.1MPa, shape fixation rate of 97.3% and shape recovery rate of 98.7%, which can be used for clinical treatment. To verify the biocompatibility of the polymer, we inoculated and cultured human umbilical vein endothelial cells on the polymer, and performed subcutaneous implantation on the back of Bal/c mice for 12 weeks. The results showed low cytotoxicity and excellent biocompatibility of the polymer, and the antibacterial activity of the polymer was improved due to the presence of DMAEMA. To verify the blood compatibility of the polymer, we performed blood compatibility experiments with fresh blood from healthy volunteers, and the results showed that the polymer prevented platelet aggregation and hemolysis. Finally, the structure of the branch stent was designed by Blender 3D modeling software and a branch stent was printed by DLP printer. Therefore, shape memory branch vascular stents based on 4D printing may be promising for personalized and complete endovascular treatment of aortic dissection, abdominal aortic aneurysm and other diseases.

MOST Discipline Catalogue医学 - 临床医学 - 外科学
URL查看原文
Language中文
Other Code262010_220200903951
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/535952
Collection第二临床医学院
Affiliation
兰州大学第二临床医学院
Recommended Citation
GB/T 7714
顾浩. 4D打印形状记忆分支血管支架的制备 及性能研究[D]. 兰州. 兰州大学,2023.
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