【摘要】：心血管疾病是危害人類(lèi)健康的常見(jiàn)疾病之一，對(duì)于問(wèn)題比較嚴(yán)重的患者，最常用的治療手段及輔助治療手段就是血管移植手術(shù)[9]，因此移植血管的來(lái)源就成為一個(gè)很關(guān)鍵的問(wèn)題。解決這一問(wèn)題的一個(gè)重要手段就是構(gòu)建人工血管。合成高分子聚合物材料人工血管在代用大動(dòng)脈血管方面已經(jīng)取得了較滿意的效果，然而在中動(dòng)脈、小動(dòng)脈和靜脈(6mm)外科手術(shù)上，由于合成材料引起的小口徑人工血管血管栓塞、內(nèi)膜增生等問(wèn)題難以徹底解決，仍難以滿足臨床的要求[3]。因此，可保持血流長(zhǎng)期通暢的小口徑人工血管的構(gòu)建就成為國(guó)內(nèi)外對(duì)人工血管研究的一個(gè)熱點(diǎn)問(wèn)題。 殼聚糖是甲殼素經(jīng)脫乙�；笾频玫囊环N天然聚陽(yáng)離子功能性多糖，具有生物可降解性和無(wú)毒副作用等特性，在生物醫(yī)用材料和組織工程領(lǐng)域得到了廣泛的研究和應(yīng)用。本實(shí)驗(yàn)以殼聚糖纖維為主要材料，，制備了一種新型可降解的小口徑殼聚糖人工血管，以期解決目前臨床上小口徑人工血管短缺的問(wèn)題。 本實(shí)驗(yàn)取得了以下幾個(gè)方面的成果和進(jìn)展。 1.對(duì)制備的小口徑人工血管的理化性質(zhì)、機(jī)械強(qiáng)度進(jìn)行了較全面評(píng)價(jià)。人工血管理化性質(zhì)指標(biāo)包括干燥失重、灰分、重金屬含量；人工血管機(jī)械強(qiáng)度指標(biāo)包括壁厚、吸水率、水滲透壓、水滲透量、縱向最大拉伸力、加壓破裂強(qiáng)度、耐縫合強(qiáng)度。結(jié)果表明，人工血管干燥失重10.05%，灰分0.28%，重金屬含量10ug/g；小口徑人工血管壁厚為0.54±0.022mm,吸水率226.02±8.17%，水滲透壓39.25±3.35mmHg，水滲透量4.90±0.47ml，縱向最大拉伸力8.58±1.98N (干態(tài)下)，加壓破裂強(qiáng)度1986±247mmHg (濕態(tài)下)，耐縫合強(qiáng)度3.87±0.43N (濕態(tài)下)。本文全面的評(píng)價(jià)了這種可降解的殼聚糖基小口徑人工血管的機(jī)械強(qiáng)度，為殼聚糖基類(lèi)可降解的人工血管性質(zhì)測(cè)定提供一定的參考依據(jù)。 2.對(duì)制備的小口徑人工血管的生物相容性和生物安全性進(jìn)行了評(píng)價(jià)。結(jié)果表明，人工血管在體外可以穩(wěn)定持續(xù)的降解，人工血管的肝素可以在較長(zhǎng)時(shí)間內(nèi)穩(wěn)定、持續(xù)釋放，使人工血管保持較長(zhǎng)時(shí)間的抗凝活性；人臍靜脈血管內(nèi)皮細(xì)胞在人工血管膜片上體外貼附生長(zhǎng)良好，人工血管皮下和肌肉植入后組織炎癥反應(yīng)較輕，無(wú)溶血、無(wú)血小板吸附、無(wú)細(xì)胞毒性、無(wú)急性全身毒性及皮下刺激反應(yīng)等不良反應(yīng)。 3.對(duì)小口徑人工血管的動(dòng)物植入可行性進(jìn)行了初步試驗(yàn)。狗股動(dòng)脈體內(nèi)置換實(shí)驗(yàn)結(jié)果表明明，人工血管可在體內(nèi)逐步降解并原位誘導(dǎo)新生血管并保持血流長(zhǎng)期通暢，新生血管組織學(xué)觀察和免疫組化及掃描電鏡分析結(jié)果表明，新生血管已經(jīng)形成天然血管的組織結(jié)構(gòu)。
[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 鹵0.022 mm, the water absorption rate was 226.02 鹵8.17 mm, the water osmotic pressure was 39.25 鹵3.35 mm Hg, the water osmotic capacity was 4.90 鹵0.47 ml, the longitudinal maximum tensile force was 8.58 鹵1.98 N (under dry condition), the compressive rupture strength was 1986 鹵247mmHg (under wet condition), and the suture strength was 3.87 鹵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.
【學(xué)位授予單位】：中國(guó)海洋大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R318.11

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