壳聚糖小口径可降解人工血管生物学性质与应用研究

发布时间：2018-07-30 06:16

【摘要】：心血管疾病是危害人类健康的常见疾病之一，对于问题比较严重的患者，最常用的治疗手段及辅助治疗手段就是血管移植手术[9]，因此移植血管的来源就成为一个很关键的问题。解决这一问题的一个重要手段就是构建人工血管。合成高分子聚合物材料人工血管在代用大动脉血管方面已经取得了较满意的效果，然而在中动脉、小动脉和静脉(6mm)外科手术上，由于合成材料引起的小口径人工血管血管栓塞、内膜增生等问题难以彻底解决，仍难以满足临床的要求[3]。因此，可保持血流长期通畅的小口径人工血管的构建就成为国内外对人工血管研究的一个热点问题。壳聚糖是甲壳素经脱乙酰基后制得的一种天然聚阳离子功能性多糖，具有生物可降解性和无毒副作用等特性，在生物医用材料和组织工程领域得到了广泛的研究和应用。本实验以壳聚糖纤维为主要材料，，制备了一种新型可降解的小口径壳聚糖人工血管，以期解决目前临床上小口径人工血管短缺的问题。本实验取得了以下几个方面的成果和进展。 1.对制备的小口径人工血管的理化性质、机械强度进行了较全面评价。人工血管理化性质指标包括干燥失重、灰分、重金属含量；人工血管机械强度指标包括壁厚、吸水率、水渗透压、水渗透量、纵向最大拉伸力、加压破裂强度、耐缝合强度。结果表明，人工血管干燥失重10.05%，灰分0.28%，重金属含量10ug/g；小口径人工血管壁厚为0.54±0.022mm,吸水率226.02±8.17%，水渗透压39.25±3.35mmHg，水渗透量4.90±0.47ml，纵向最大拉伸力8.58±1.98N (干态下)，加压破裂强度1986±247mmHg (湿态下)，耐缝合强度3.87±0.43N (湿态下)。本文全面的评价了这种可降解的壳聚糖基小口径人工血管的机械强度，为壳聚糖基类可降解的人工血管性质测定提供一定的参考依据。 2.对制备的小口径人工血管的生物相容性和生物安全性进行了评价。结果表明，人工血管在体外可以稳定持续的降解，人工血管的肝素可以在较长时间内稳定、持续释放，使人工血管保持较长时间的抗凝活性；人脐静脉血管内皮细胞在人工血管膜片上体外贴附生长良好，人工血管皮下和肌肉植入后组织炎症反应较轻，无溶血、无血小板吸附、无细胞毒性、无急性全身毒性及皮下刺激反应等不良反应。 3.对小口径人工血管的动物植入可行性进行了初步试验。狗股动脉体内置换实验结果表明明，人工血管可在体内逐步降解并原位诱导新生血管并保持血流长期通畅，新生血管组织学观察和免疫组化及扫描电镜分析结果表明，新生血管已经形成天然血管的组织结构。
[Abstract]:Cardiovascular disease is one of the common diseases harmful to human health. For patients with serious problems, vascular transplantation is the most commonly used treatment and auxiliary treatment, so the source of vascular graft has become a key issue. An important way to solve this problem is to construct artificial blood vessels. The synthetic polymer materials have achieved satisfactory results in the replacement of great arteries. However, in the middle artery, arterioles and veins (6mm) surgery, the small diameter artificial vascular embolism caused by synthetic materials has been achieved. Endometrial hyperplasia and other problems are difficult to solve, but still difficult to meet the clinical requirements [3]. Therefore, the construction of small diameter artificial blood vessels which can keep blood flow unobstructed for a long time has become a hot issue in the research of artificial blood vessels at home and abroad. Chitosan is a kind of natural polycationic functional polysaccharide prepared by deacetylation of chitin. It has been widely studied and applied in biomedical materials and tissue engineering because of its biodegradability and non-toxic side effects. In this experiment, a new biodegradable small diameter chitosan artificial blood vessel was prepared with chitosan fiber as the main material, in order to solve the problem of shortage of small diameter artificial blood vessel in clinic. This experiment has made the following achievements and progress. 1. The physical and chemical properties and mechanical strength of the small diameter artificial blood vessels were comprehensively evaluated. The physical and chemical properties of artificial blood vessel include dry weight loss, ash content, heavy metal content, and mechanical strength indexes include wall thickness, water absorption, water osmotic pressure, water osmotic capacity, longitudinal maximum tensile force, compressive rupture strength and suture strength. The results showed that the weight loss of artificial blood vessel was 10.05%, the ash content was 0.28% and the heavy metal content was 10 ugr / g; The wall thickness of small diameter artificial vessels was 0.54 卤0.022 mm, the water absorption rate was 226.02 卤8.17 mm, the water osmotic pressure was 39.25 卤3.35 mm Hg, the water osmotic capacity was 4.90 卤0.47 ml, the longitudinal maximum tensile force was 8.58 卤1.98 N (under dry condition), the compressive rupture strength was 1986 卤247mmHg (under wet condition), and the suture strength was 3.87 卤0.43 N (wet state). In this paper, the mechanical strength of the biodegradable chitosan based small diameter artificial blood vessel is comprehensively evaluated, which provides a certain reference for the determination of the properties of the biodegradable chitosan artificial blood vessel. 2. The biocompatibility and safety of small diameter artificial blood vessels were evaluated. The results showed that the artificial blood vessel could degrade steadily in vitro, heparin of the artificial blood vessel could be stable and released for a long time, and the anticoagulant activity of the artificial blood vessel could be maintained for a long time. The endothelial cells of human umbilical vein were attached to the artificial vascular membrane in vitro and grew well. The inflammatory reaction of the tissue was mild, no hemolysis, no platelet adsorption, no cytotoxicity, no hemolysis, no platelet adsorption, no cytotoxicity, no inflammation, no hemolysis, no platelet adsorption and no cytotoxicity. No adverse reactions such as acute systemic toxicity and subcutaneous irritation. The feasibility of small diameter artificial blood vessel implantation in animals was preliminarily tested. The results of in vivo replacement of femoral artery in dogs showed that the artificial vessels could be degraded in vivo and induced in situ to keep the blood flow unobstructed for a long time. The results of histological observation, immunohistochemistry and scanning electron microscopy showed that, Neovascularization has formed the tissue structure of natural blood vessels.
【学位授予单位】：中国海洋大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R318.11

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