【摘要】：目前,人工血管移植術(shù)是醫(yī)治心血管疾病的一種有效的手術(shù)方法。然而,由于人工血管表面缺乏活性內(nèi)皮層,人工血管特別是小口徑人工血管經(jīng)常會(huì)遇到通暢率低和再狹窄等問題,從而限制了其在臨床上的應(yīng)用。相關(guān)研究發(fā)現(xiàn),人工血管的快速內(nèi)皮化有助于改善上述問題。伴隨著基因治療的發(fā)展,使用基因轉(zhuǎn)染技術(shù)加速血管內(nèi)皮細(xì)胞增殖受到了越來越多的關(guān)注。本論文利用靜電紡絲以及靜電噴霧技術(shù),成功構(gòu)建了由靶向內(nèi)皮細(xì)胞增殖的基因復(fù)合物修飾的電紡血管纖維膜,在此基礎(chǔ)上,制備出了復(fù)合小口徑人工血管,其研究結(jié)果概括如下:1.通過靜電噴霧技術(shù),將具有靶向性的聚陽離子基因載體微粒(MPs)以及其與pZNF580基因形成的復(fù)合物(MPs-pZNF580),負(fù)載在聚己內(nèi)酯(PCL)和聚-3S-嗎啉-1-異丁基-2,5-二酮(PIBMD)嵌段共聚物所制備的電紡PCL-PIBMD纖維膜表面,隨著MPs以及MPs-pZNF580的加入,PCL-PIBMD纖維的直徑和機(jī)械性能沒有明顯變化,但是改性后的PCL-PIBMD/MPs以及PCL-PIBMD/MPspZNF580纖維膜的親水性能有所提高,通過血小板黏附實(shí)驗(yàn)證明,PCLPIBMD/MPs以及PCL-PIBMD/MPs-pZNF580纖維膜比空白PCL-PIBMD纖維膜具有更好的血液相容性。細(xì)胞活性測試以及熒光染色表明,經(jīng)過7天的培養(yǎng),PCLPIBMD/MPs-pZNF580纖維膜表面相對細(xì)胞數(shù)達(dá)到121.5%±1.2%,細(xì)胞密度達(dá)到749細(xì)胞/平方毫米,表明該纖維膜能夠明顯地促進(jìn)內(nèi)皮細(xì)胞(EA.hy926 cells)的增殖。2.采取大鼠背部皮下埋植模型評價(jià)纖維膜的組織相容性。相較于PCLPIBMD以及PCL-PIBMD/MPs對照組,由MPs-pZNF580修飾的PCL-PIBMD纖維膜表現(xiàn)出最少的急性炎癥反應(yīng)。3.利用多層靜電紡絲技術(shù),制備了以PCL-PIBMD/MPs-pZNF580為內(nèi)層,聚碳酸酯-聚氨酯(PCU)為外層的復(fù)合小口徑人工血管,兔頸動(dòng)脈移植實(shí)驗(yàn)結(jié)果顯示該復(fù)合小口徑血管具有良好的通暢率,表明其在血管組織工程中具有良好的應(yīng)用前景。
[Abstract]:At present, artificial vascular transplantation is an effective surgical method for the treatment of cardiovascular diseases. However, due to the lack of active endodermis on the surface of artificial vessels, especially small-diameter artificial vessels, often encounter problems such as low patency rate and restenosis, which limits its clinical application. Related studies have found that the rapid endothelium of artificial blood vessels can help to improve the above-mentioned problems. With the development of gene therapy, more and more attention has been paid to accelerating the proliferation of vascular endothelial cells by gene transfection. In this paper, the electrospun vascular fiber membrane was successfully constructed by electrospinning and electrostatic spray. On the basis of this, the composite small diameter artificial blood vessel was prepared, which was modified by the gene complex of endothelial cell proliferation. The results of the study are summarized as follows: 1. The targeting polycationic gene carrier particle (MPs) and its complex with pZNF580 gene (MPs-pZNF580) were prepared by electrostatic spray technique. Supported on the surface of electrospun PCL-PIBMD fiber membrane prepared by polycaprolactone (PCL) and poly-3S-morpholine-1-isobutyl-2,5-dione (PIBMD) block copolymer, with the addition of MPs and MPs-pZNF580, The diameter and mechanical properties of PCL-PIBMD fiber did not change obviously, but the hydrophilicity of modified PCL-PIBMD/MPs and PCL-PIBMD/MPspZNF580 fiber membrane was improved. PCLPIBMD/MPs and PCL-PIBMD/MPs-pZNF580 fiber membrane have better blood compatibility than blank PCL-PIBMD fiber membrane. Cell viability test and fluorescence staining showed that after 7 days of culture, the relative number of cells on the surface of PCLPIBMD/MPs-pZNF580 fiber membrane reached 121.5% 鹵1.2%, and the cell density reached 749 cells / square millimeter. The results show that the fiber membrane can significantly promote the proliferation of endothelial cells (EA.hy926 cells). 2. The histocompatibility of fibrous membrane was evaluated by subcutaneous implantation model in rats. Compared with the PCLPIBMD and PCL-PIBMD/MPs control groups, the PCL-PIBMD fibrous membrane modified by MPs-pZNF580 showed the least acute inflammatory reaction. 3. The composite small diameter artificial blood vessel with PCL-PIBMD/MPs-pZNF580 as inner layer and polycarbonate-polyurethane (PCU) as outer layer was prepared by multi-layer electrospinning technology. The experimental results of rabbit carotid artery transplantation show that the composite small diameter vessel has a good patency rate, indicating that it has a good application prospect in vascular tissue engineering.
【學(xué)位授予單位】：天津大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R318.08;TQ340.64

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