本文選題：心血管支架功能涂層　切入點(diǎn)：原位內(nèi)皮化　出處：《浙江大學(xué)》2012年碩士論文

【摘要】：心血管植入材料在心血管疾病治療中發(fā)揮重要作用的同時(shí),依然面臨包括凝血,術(shù)后再狹窄等一系列挑戰(zhàn)。具有血管原位內(nèi)皮再生功能的材料是實(shí)現(xiàn)心血管組織再生的重要物質(zhì)基礎(chǔ)。由于生命體系的復(fù)雜性,構(gòu)建具有內(nèi)皮細(xì)胞選擇性誘導(dǎo)功能的涂層材料,實(shí)現(xiàn)復(fù)雜體系中血管內(nèi)皮細(xì)胞的選擇性誘導(dǎo)是實(shí)現(xiàn)血管原位內(nèi)皮再生功能的關(guān)鍵。含有兩性離子基團(tuán)的化合物,不僅可以明顯改善材料的血液相容性,而且可以實(shí)現(xiàn)對(duì)蛋白質(zhì),血小板和細(xì)胞的非特異性阻抗,已成為心血管植入材料界面修飾的有效手段之一。而基于羧酸甜菜堿的兩性離子聚合物近年來(lái)也成為生物材料表面修飾改性的研究熱點(diǎn),其結(jié)構(gòu)與磷酸膽堿基團(tuán)類似,具有優(yōu)良的生物抗污性能,且具有更簡(jiǎn)單的合成方法和穩(wěn)定性。此外,羧酸甜菜堿表面的羧基可與生物分子的氨基共價(jià)鍵合,為實(shí)現(xiàn)界面功能化設(shè)計(jì)提供了有效手段。 本研究以羧酸甜菜堿兩性電荷聚合物為基礎(chǔ),設(shè)計(jì)構(gòu)建具有良好生物抗污性能和血液相容性的涂層材料,并在涂層表面固定具有內(nèi)皮細(xì)胞選擇能力的活性短肽REDV (Arg-Glu-Asp-Val)。探索羧酸甜菜堿基團(tuán)的非特異性阻抗和REDV短肽的特異性誘導(dǎo)協(xié)同作用制備具有內(nèi)皮細(xì)胞選擇性功能的涂層設(shè)計(jì)。 研究采用自由基共聚的方法得到了不同親疏水比例的甲基丙烯酸羧酸甜菜堿酯(CBMA)和甲基丙烯酸正丁酯(BMA)的無(wú)規(guī)共聚物,通過調(diào)節(jié)聚合單體組成功制備能穩(wěn)定存在于基材表面的可功能化涂層,進(jìn)一步通過NHS/EDC活化涂層表面的羧基,與短肽REDV的氨基反應(yīng),將短肽固定在涂層表面。并完成對(duì)REDV功能化羧酸甜菜堿共聚物涂層基礎(chǔ)理化性質(zhì)的表征。此外,蛋白質(zhì)吸附和體外血液相容性實(shí)驗(yàn)結(jié)果表明,固定短肽后,涂層仍具有明顯的抗蛋白質(zhì)吸附能力,并具有優(yōu)良的抗凝血、抗血小板吸附能力。 本研究著重對(duì)人臍靜脈內(nèi)皮細(xì)胞(HUVEC)和人臍動(dòng)脈平滑肌細(xì)胞(HUASMC)在REDV功能化羧酸甜菜堿共聚物涂層表面的生長(zhǎng)行為進(jìn)行了表征。細(xì)胞粘附和增殖實(shí)驗(yàn)結(jié)果表明,功能化羧酸甜菜堿共聚物涂層表面的內(nèi)皮細(xì)胞選擇性是通過羧酸甜菜堿組分對(duì)平滑肌細(xì)胞的非特異性阻抗及REDV短肽對(duì)內(nèi)皮細(xì)胞的特異性誘導(dǎo)作用共同實(shí)現(xiàn)的,羧酸甜菜堿組分的引入,提高了涂層對(duì)內(nèi)皮細(xì)胞的選擇能力,抑制了平滑肌細(xì)胞的生長(zhǎng)和遷移。且在較復(fù)雜的共培養(yǎng)體系中,這種對(duì)內(nèi)皮細(xì)胞的高選擇性依然存在。 本工作成功構(gòu)建了具有良好的生物抗污能力、血液相容性及內(nèi)皮細(xì)胞選擇性的REDV功能化羧酸甜菜堿共聚物涂層,為進(jìn)一步將兩性甜菜堿聚合物應(yīng)用于心血管支架表面改性提供了基礎(chǔ)。
[Abstract]:While cardiovascular implants play an important role in the treatment of cardiovascular disease, they still face the challenge of including coagulation. A series of challenges such as restenosis after operation. Materials with vascular in situ endothelial regeneration function are the important material basis for cardiovascular tissue regeneration. Due to the complexity of life system, the coating material with selective induction function of endothelial cells is constructed. Selective induction of vascular endothelial cells in complex systems is the key to the function of vascular in situ endothelial regeneration. Compounds containing amphoteric groups can not only significantly improve the blood compatibility of the materials, but also achieve proteins. Non-specific impedance of platelets and cells has become one of the effective methods for interfacial modification of cardiovascular implants. Amphoteric polymers based on carboxylate betaine have become the research focus of surface modification of biomaterials in recent years. Its structure is similar to that of choline phosphate group, it has excellent biological antifouling property, and it has simpler synthesis method and stability. In addition, the carboxyl group on the surface of carboxylate betaine can be covalently bonded with the amino group of biomolecules. It provides an effective means to realize interface function design. Based on the amphoteric charge polymer of carboxylate betaine, a coating material with good biodegradability and blood compatibility was designed and constructed. The active short peptide REDV (Arg-Glu-Asp-Valan) with endothelial cell selection was immobilized on the surface of the coating. The nonspecific impedance of carboxylate betaine group and the specific induction of REDV short peptide were investigated to prepare the coating with selective endothelial cell function. The random copolymers of betaine methacrylate (CBMA) and butyl methacrylate (BMA) with different hydrophilic ratios were prepared by free radical copolymerization. The functional coatings, which can stably exist on the substrate surface, were successfully prepared by adjusting the polymerization monomer group. The carboxyl group on the surface of the coating was further activated by NHS/EDC and reacted with the amino group of the short peptide REDV. The basic physical and chemical properties of REDV functionalized carboxylate betaine copolymer coating were characterized. The coating still has obvious anti-protein adsorption ability, and excellent anticoagulant and anti-platelet adsorption ability. The growth behavior of human umbilical vein endothelial cells (HUVECs) and human umbilical artery smooth muscle cells (HUASMCs) on the surface of REDV functionalized carboxylate betaine copolymer coating was studied. The selectivity of endothelial cells on the surface of functionalized carboxylate betaine copolymers was achieved through the nonspecific impedance of carboxylate betaine components to smooth muscle cells and the specific induction of REDV short peptides to endothelial cells. The introduction of carboxylate betaine enhanced the ability of coating to select endothelial cells and inhibited the growth and migration of smooth muscle cells. In this work, a REDV functionalized carboxylate betaine copolymer coating with good bioantifouling ability, blood compatibility and endothelial cell selectivity was successfully constructed. It provides a basis for the further application of amphoteric betaine polymer in the surface modification of cardiovascular stent.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.08

【參考文獻(xiàn)】

相關(guān)期刊論文 前8條

1 楊君;一氧化氮與PTCA術(shù)后再狹窄的防治[J];國(guó)外醫(yī)學(xué)(內(nèi)科學(xué)分冊(cè));2002年08期

2 張琳;張瑞巖;;藥物洗脫支架術(shù)后再內(nèi)皮化延遲與晚期血栓形成[J];國(guó)際心血管病雜志;2009年02期

3 潘 勇,艾玉峰,熊 猛,張琳西,夏文森,彭 湃,黃 蔚,趙玉峰;體外組織工程血管支架內(nèi)皮化的實(shí)驗(yàn)研究[J];中國(guó)美容醫(yī)學(xué);2002年04期

4 張露;劉必成;;構(gòu)建抗體微陣列過程中抗體固定的策略[J];生物醫(yī)學(xué)工程學(xué)雜志;2006年04期

5 王鶴;馬莉;;血管內(nèi)皮細(xì)胞功能損傷與保護(hù)的研究進(jìn)展[J];實(shí)用醫(yī)學(xué)雜志;2008年10期

6 白旭芳;冠脈內(nèi)支架內(nèi)皮化研究進(jìn)展[J];中國(guó)心血管雜志;1998年03期

7 劉錄山;王貴學(xué);;心血管移植物體外內(nèi)皮化研究進(jìn)展[J];中國(guó)醫(yī)療器械信息;2006年07期

8 薛冠華,張紀(jì)蔚,張柏根;人工血管內(nèi)皮化的研究進(jìn)展[J];中國(guó)實(shí)用外科雜志;2002年03期

相關(guān)碩士學(xué)位論文 前1條

1 王曉麗;介入治療材料表面的血液相容性修飾[D];浙江大學(xué);2006年

，

本文編號(hào)：1663567