可降解小口径人工血管的生物相容性和功效性研究

发布时间：2018-03-04 09:27

  本文选题：小口径人工血管　切入点：生物相容性　出处：《中国海洋大学》2014年博士论文　论文类型：学位论文

【摘要】：心血管疾病和外周动静脉疾病严重威胁人类健康，对较严重患者需进行血管置换。通常，血管置换的金标准是采用大隐静脉或乳内动脉对体内病损血管进行旁路搭桥手术或原位置换。但往往由于病人自身身体状况限制,自体血管无法应用，而顺应性与自体血管相近的同种异体或异体血管又涉及到免疫排斥等问题。因此，合成类人工血管吸引了科研工作者的广泛关注并在主动脉夹层等大血管病变的置换中取得了很好的效果。然而对于小血管病变（内径6mm），合成类人工血管、组织工程化血管均因易导致早期血管内膜增生或血栓形成而致使移植失败。因此，生物相容性良好并具备一定机械强度的小口径人工血管成为研究重点。本文利用生物相容性良好的壳聚糖纤维为骨架，辅以明胶和肝素，经过交联后制成可降解小口径人工血管；并对其理化性质、机械性能、生物安全性、主要成分－壳聚糖的代谢情况及其功效性进行了研究。 本实验取得了如下成果和进展： 1.对制备的小口径人工血管的理化性质、机械强度进行了较为全面的评价。人工血管的理化性质主要对灰分、干燥失重、重金属、细菌内毒素以及热原等指标进行了测定，结果表明：灰分为0.4%，干燥失重为13%，重金属小于10μg/g，细菌内毒素0.25EU/mg，热原低于1.3℃；机械强度指标主要测定了顺应性、孔隙率、纵向抗拉伸强度、爆破压和耐缝合强度等指标，结果显示：人工血管顺应性较天然血管低，纵向拉伸强度强于大鼠腹主动脉但低于犬股动脉，爆破压高于天然动脉血管，耐缝合强度强于大鼠腹主动脉，孔隙率为96.24%±3.99%。 2.对人工血管的生物安全性和生物相容性进行了全面的评价。人工血管浸提液细胞毒性和内腔细胞相容性均符合要求；体外血液相容性实验显示：人工血管无血栓形成，无溶血，无血小板吸附，凝血四项显示抗凝血良好；人工血管体内植入后炎症反应较轻，至人工血管降解完全，炎症反应消失，肝素随人工血管的降解、逐渐释放，能满足人工血管前期抗凝血要求；人工血管无急性全身毒性；综上，人工血管生物相容性和生物安全性良好。 3.对人工血管骨架材料－壳聚糖进行代谢研究。壳聚糖降解产物在肝脏、脾脏、肾脏、心脏和脑中均有分布，其中肝脏和肾脏中含量较多；脾脏，心脏和脑中含量较少；尿液是壳聚糖代谢的主要途径，尿中代谢的壳聚糖降解产物分子量低于65kDa。 4.对人工血管的功效性进行评价。选择比格犬为实验动物，对犬股动脉血管进行人工血管置换，，特异性染色显示，人工血管形成了胶原纤维和弹力纤维，且与正常血管无显著性差异。人工血管形成了天然血管所具备的三层细胞结构（由内至外分别为血管内皮细胞，血管平滑肌细胞和成纤维细胞）。 综上，该小口径人工血管具有良好的生物相容性及功效性，满足体内应用的要求。
[Abstract]:Cardiovascular diseases and peripheral arteriovenous diseases pose a serious threat to human health, requiring vascular replacement in more severe patients. The gold standard for vascular replacement is bypass grafting or in situ replacement of diseased blood vessels in the body using the great saphenous vein or the internal mammary artery. However, compliance with autogenous blood vessels, such as allograft or allograft, is related to immune rejection and so on. Synthetic artificial vasculature has attracted extensive attention of researchers and has achieved good results in the replacement of large vascular diseases such as aortic dissection. Tissue engineered blood vessels fail because they are prone to early intimal hyperplasia or thrombosis. Small diameter artificial blood vessels with good biocompatibility and certain mechanical strength have become the focus of research. In this paper, chitosan fibers with good biocompatibility were used as the skeleton, supplemented with gelatin and heparin. The biodegradable small diameter artificial blood vessels were prepared after crosslinking, and their physicochemical properties, mechanical properties, biological safety, metabolism and efficacy of chitosan were studied. The results and progress of this experiment are as follows:. 1. The physical and chemical properties and mechanical strength of the small diameter artificial blood vessels were comprehensively evaluated. The indexes of ash, dry weight loss, heavy metal, bacterial endotoxin and pyrogen were mainly determined by the physical and chemical properties of the artificial blood vessels, such as ash content, dry weight loss, heavy metal content, bacterial endotoxin and pyrogen. The results showed that the ash content was 0.4m, dry weight loss was 13g, heavy metal was less than 10 渭 g / g, bacterial endotoxin was 0.25 EU.mg, pyrogen was lower than 1.3 鈩

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