本文選題：小口徑人工血管　切入點：生物相容性　出處：《中國海洋大學》2014年博士論文　論文類型：學位論文

【摘要】：心血管疾病和外周動靜脈疾病嚴重威脅人類健康，對較嚴重患者需進行血管置換。通常，血管置換的金標準是采用大隱靜脈或乳內動脈對體內病損血管進行旁路搭橋手術或原位置換。但往往由于病人自身身體狀況限制,自體血管無法應用，而順應性與自體血管相近的同種異體或異體血管又涉及到免疫排斥等問題。因此，合成類人工血管吸引了科研工作者的廣泛關注并在主動脈夾層等大血管病變的置換中取得了很好的效果。然而對于小血管病變（內徑6mm），合成類人工血管、組織工程化血管均因易導致早期血管內膜增生或血栓形成而致使移植失敗。因此，生物相容性良好并具備一定機械強度的小口徑人工血管成為研究重點。本文利用生物相容性良好的殼聚糖纖維為骨架，輔以明膠和肝素，經過交聯(lián)后制成可降解小口徑人工血管；并對其理化性質、機械性能、生物安全性、主要成分－殼聚糖的代謝情況及其功效性進行了研究。 本實驗取得了如下成果和進展： 1.對制備的小口徑人工血管的理化性質、機械強度進行了較為全面的評價。人工血管的理化性質主要對灰分、干燥失重、重金屬、細菌內毒素以及熱原等指標進行了測定，結果表明：灰分為0.4%，干燥失重為13%，重金屬小于10μg/g，細菌內毒素0.25EU/mg，熱原低于1.3℃；機械強度指標主要測定了順應性、孔隙率、縱向抗拉伸強度、爆破壓和耐縫合強度等指標，結果顯示：人工血管順應性較天然血管低，縱向拉伸強度強于大鼠腹主動脈但低于犬股動脈，爆破壓高于天然動脈血管，耐縫合強度強于大鼠腹主動脈，孔隙率為96.24%±3.99%。 2.對人工血管的生物安全性和生物相容性進行了全面的評價。人工血管浸提液細胞毒性和內腔細胞相容性均符合要求；體外血液相容性實驗顯示：人工血管無血栓形成，無溶血，無血小板吸附，凝血四項顯示抗凝血良好；人工血管體內植入后炎癥反應較輕，至人工血管降解完全，炎癥反應消失，肝素隨人工血管的降解、逐漸釋放，能滿足人工血管前期抗凝血要求；人工血管無急性全身毒性；綜上，人工血管生物相容性和生物安全性良好。 3.對人工血管骨架材料－殼聚糖進行代謝研究。殼聚糖降解產物在肝臟、脾臟、腎臟、心臟和腦中均有分布，其中肝臟和腎臟中含量較多；脾臟，心臟和腦中含量較少；尿液是殼聚糖代謝的主要途徑，尿中代謝的殼聚糖降解產物分子量低于65kDa。 4.對人工血管的功效性進行評價。選擇比格犬為實驗動物，對犬股動脈血管進行人工血管置換，，特異性染色顯示，人工血管形成了膠原纖維和彈力纖維，且與正常血管無顯著性差異。人工血管形成了天然血管所具備的三層細胞結構（由內至外分別為血管內皮細胞，血管平滑肌細胞和成纖維細胞）。 綜上，該小口徑人工血管具有良好的生物相容性及功效性，滿足體內應用的要求。
[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

本文編號：1565101