静电纺聚氨酯基小口径人造血管的构建与性能研究

发布时间：2018-07-06 19:10

本文选题：静电纺丝 + 聚氨酯　；参考：《天津大学》2012年博士论文

【摘要】：随着组织工程发展，通过静电纺丝技术构建既具有生物相容性又有合适机械性能的小口径血管成为研究热点。本论文通过共混和复合静电纺丝技术构建了聚氨酯(PU)基的具有良好生物相容性的小口径血管支架。其研究成果概括如下： 1.通过共混的方式将亲水性的聚乙二醇(PEG)引入PU纤维支架内部，，混合PU/PEG纤维支架的纤维直径随着PEG的加入降低，孔隙率增大；支架表面的亲水性随着PEG含量的增加而显著增加。PEG结晶导致混合纤维支架的力学强度提高；通过血小板黏附实验和溶血率结果证明，混合PU/PEG纤维支架比空白PU支架具有更好的血液相容性。脐静脉内皮细胞(HUVECs)黏附实验表明，当PEG含量为20%和30%时，最利于细胞的黏附和增殖。 2.通过乳液电纺技术将抗凝血的肝素钠引入电纺PU/PEG纤维支架中，结果表明肝素钠在体内最初24小时呈现突释的现象，紧接着是一个稳定的释放期，随着药物含量的增加，药物释放量减少，其释放符合Fickian扩散释放机理。血小板黏附实验和溶血率实验结果表明，肝素钠的加入可以明显提高支架表面长时间血液接触的抗凝血性能。肝素钠能够支持HUVECs在纤维支架上更好的黏附与生长，同时抑制小鼠的平滑肌细胞(VCMCs)生长及增殖。 3.通过原位光聚合静电纺丝技术将聚乙二醇单丙烯酸酯(PEGMA)交联固定在PU纤维支架上，当PU/PEGMA的质量比为90/10和80/20时，纤维的平均直径分别为622±110nm和547±77nm，较少的PEGMA的加入就能显著提高混合支架的力学强度，同时纤维的形貌能够得到较好保持。混合纤维支架的亲水性可以通过改变PU/PEGMA的比率进行调节，合适的亲水性表面（接触角在55-75o）能够支持HUVECs更好的生长及增殖。 4.采用分层复合静电纺丝技术构建了PU/明胶-肝素钠复合小口径血管，复合管状支架内层为负载肝素钠的明胶纳米纤维组成，内层纤维支架的孔隙率可以达到70%,明胶内层通过戊二醛蒸汽交联，可以使支架的质量损失率大大降低，保证支架在应用时的性能的稳定。PU外层由平均直径784±312nm的纤维组成，平均孔径为1.6μm。力学性能测试证明弹性PU外层能够提高支架的柔韧性同时降低明胶基内层的刚性。明胶基的纳米纤维支架能够支持HUVECs的黏附与增殖，血小板黏附实验和溶血实验证明支架具有很好的血液相容性。
[Abstract]:With the development of tissue engineering, it has become a research focus to construct small diameter vessels with biocompatibility and suitable mechanical properties by electrostatic spinning technology. In this paper, polyurethane (pu) based small diameter vascular stent with good biocompatibility was constructed by blending and composite electrospinning technology. The research results are summarized as follows: 1. The hydrophilic polyethylene glycol (PEG) was introduced into the pu fiber scaffold by blending. The fiber diameter of the mixed pu / PEG fiber scaffold decreased with the addition of PEG and the porosity increased. The hydrophilicity of the scaffold surface increased significantly with the increase of PEG content. The mechanical strength of the scaffold increased with the increase of PEG content, and the results of platelet adhesion test and hemolysis rate showed that the hydrophilicity of the scaffold increased with the increase of PEG content. The mixed pu / PEG fiber scaffold has better blood compatibility than the blank pu scaffold. Umbilical vein endothelial cells (HUVECs) adhesion assay showed that when PEG content was 20% and 30%, the adhesion and proliferation of HUVECs were the best. 2. The anticoagulant sodium heparin was introduced into the electrospun PUP / PEG fiber scaffold by emulsion electrospinning technology. The results showed that heparin sodium showed sudden release in the first 24 hours of the body, followed by a stable release period, with the increase of drug content. The drug release was reduced, and the release was consistent with the Fickian diffusion release mechanism. The results of platelet adhesion test and hemolysis rate test showed that heparin sodium could significantly improve the anticoagulant performance of long-term blood contact on the stent surface. Heparin sodium can support better adhesion and growth of HUVECs on fiber scaffolds and inhibit the growth and proliferation of mouse smooth muscle cells (VCMCs). Polyethylene glycol monoacrylate (PEGMA) was crosslinked and fixed on pu fiber scaffold by in situ photopolymerization electrospinning. When the mass ratio of pu / PEGMA was 90 / 10 and 80 / 20, The average diameters of the fibers were 622 卤110nm and 547 卤77nmrespectively. The mechanical strength of the mixed scaffolds could be significantly improved by adding less PEGMA, and the morphology of the fibers could be maintained. The hydrophilicity of mixed fiber scaffold can be adjusted by changing the ratio of PU- / PEGMA. The suitable hydrophilic surface (contact angle is 55-75o) can support the better growth and proliferation of HUVECs. The small diameter blood vessels of PU- / gelatin-heparin sodium composite were constructed by stratified composite electrostatic spinning technique. The inner layer of the composite stent was composed of gelatin nanofibers loaded with heparin sodium. The porosity of the inner fiber scaffold can reach 70%, the gelatin inner layer can be crosslinked by glutaraldehyde steam, the mass loss rate of the scaffold can be greatly reduced, and the stability of the performance of the scaffold can be ensured. The outer layer of pu is composed of fibers with an average diameter of 784 卤312nm. The average pore size is 1.6 渭 m. The mechanical properties test showed that the elastic pu outer layer could improve the flexibility of the scaffold and reduce the rigidity of the inner layer of gelatin base. Gelatin based nanofiber scaffolds can support the adhesion and proliferation of HUVECs. Platelet adhesion and hemolysis experiments show that the scaffolds have good blood compatibility.
【学位授予单位】：天津大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R318.08

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