本文選題：內(nèi)皮祖細(xì)胞捕獲支架 + PEG-PLA-PGL/RGD涂層��； 參考：《吉林大學(xué)》2014年碩士論文

【摘要】：研究背景 冠狀動(dòng)脈支架置入術(shù)后支架內(nèi)再狹窄和血栓形成是限制冠心病介入治療發(fā)展的瓶頸，支架置入后表面早期內(nèi)皮化從而完成內(nèi)膜修復(fù)是解決再狹窄和血栓形成的關(guān)鍵。內(nèi)皮祖細(xì)胞（endothelial progenitorcell,EPC）捕獲支架通過捕獲EPC加速內(nèi)皮化，是目前研究的熱點(diǎn)。前期本研究組針對(duì)第一代藥物涂層支架延遲內(nèi)皮化的問題，將具有捕獲EPC功能的精氨酸-甘氨酸-天門冬氨酸三肽(Arg-Gly-Asp,RGD)接枝于可降解聚合物聚乙二醇-聚乳酸-聚谷氨酸共聚物[poly(ethyleneglycol)-poly (L-lactic acid)-poly (L-glutamate acid), PEG-PLA-PGL]涂層上，成功研制了新型EPC捕獲支架即PEG-PLA-PGL/RGD涂層支架，并證明了其有良好的細(xì)胞相容性。本課題在前期研究基礎(chǔ)上，進(jìn)一步對(duì)PEG-PLA-PGL/RGD涂層支架其他生物學(xué)性能進(jìn)行研究。 研究目的 評(píng)價(jià)PEG-PLA-PGL/RGD涂層支架的體外血液相容性；在證明了有良好生物相容性基礎(chǔ)上探討對(duì)內(nèi)皮細(xì)胞粘附穩(wěn)定性的影響，從而為合格新型EPC捕獲支架研制提供更多的實(shí)驗(yàn)基礎(chǔ)。 研究方法 以裸鋼片、PEG-PLA-PGL聚合物涂層鋼片為對(duì)照組，通過體外溶血實(shí)驗(yàn)、血小板吸附數(shù)量測定、抗凝血時(shí)間測定及蛋白吸附評(píng)價(jià)RGD修飾PEG-PLA-PGL共聚物（PEG-PLA-PGL/RGD）涂層鋼片的體外血液相容性。以PEG-PLA-PGL膜片為對(duì)照組,PEG-PLA-PGL/RGD膜片為實(shí)驗(yàn)組，體外在2組材料表面種植人臍靜脈內(nèi)皮細(xì)胞,流體條件下觀察在T型管及直型管不同位置、不同流速下RGD對(duì)材料表面細(xì)胞黏附穩(wěn)定性的影響。 研究結(jié)果 體外血液相容性結(jié)果：裸鋼片、 PEG-PLA-PGL組、PEG-PLA-PGL/RGD組三組鋼片溶血率均＜5%，無溶血作用；與標(biāo)本血比較，三組鋼片APTT均表現(xiàn)出明顯差異（P＜0.05），均能改善標(biāo)本血抗凝血性能；PEG-PLA-PGL涂層與裸鋼片相比，在各項(xiàng)所測指標(biāo)中無統(tǒng)計(jì)學(xué)差異；接枝RGD后PEG-PLA-PGL/RGD涂層在血小板吸附及白蛋白吸附方面優(yōu)于裸鋼片，有統(tǒng)計(jì)學(xué)差異（P＜0.05），一定程度上提高了裸鋼片的血液相容性。細(xì)胞粘附穩(wěn)定性結(jié)果：T型管及直型管各對(duì)應(yīng)位置，，PEG-PLA-PGL共聚物表面結(jié)合RGD后,細(xì)胞殘余率明顯增加（P＜0.05）；無論在對(duì)照組還是在實(shí)驗(yàn)組，T型分叉前A位置細(xì)胞殘余率都要高于分叉處及分叉后的細(xì)胞殘余率（P0.05）。 研究結(jié)論 體外實(shí)驗(yàn)證實(shí)PEG-PLA-PGL/RGD涂層支架材料具有良好的血液相容性。體外實(shí)驗(yàn)表明RGD可以提高PEG-PLA-PGL支架涂層材料的細(xì)胞粘附穩(wěn)定性，包括在T型管分叉處；但細(xì)胞粘附穩(wěn)定性受T型管分叉的影響。
[Abstract]:Background Intra-stent restenosis and thrombosis after coronary stent implantation are the bottleneck to restrict the development of coronary intervention. Early endothelialization of the surface after stent implantation is the key to resolve restenosis and thrombosis. Endothelial progenitor cells (EPC) capture scaffolds accelerate endothelialization by capturing EPC, which is a hot research topic at present. Earlier, this group focused on the delayed endothelialization of first-generation drug-coated stents. Arginine glycine aspartic acid tripeptide Arg-Gly-AspRGD was grafted onto poly(ethyleneglycol)-poly L-lactic acid)-poly L-glutamate acid (PEG-PLA-PGL) coating. A novel EPC capture scaffold PEG-PLA-PGL / RGD coated scaffold was successfully developed and proved to have good cytocompatibility. On the basis of previous studies, the other biological properties of PEG-PLA-PGL / RGD coated scaffolds were further studied in order to evaluate the in vitro blood compatibility of PEG-PLA-PGL / RGD coated scaffolds. On the basis of proved good biocompatibility, the effect on the adhesion stability of endothelial cells was discussed, which provided more experimental basis for the development of qualified new EPC capture scaffold. The study method was based on PEG-PLA-PGL polymer coated steel sheet as control group. The in vitro blood compatibility of PEG-PLA-PGL modified PEG-PLA-PGL coated steel sheet was evaluated by in vitro hemolysis test, platelet adsorption quantity measurement, anticoagulant time measurement and protein adsorption. The PEG-PLA-PGL / RGD membrane was used as the control group. Human umbilical vein endothelial cells were implanted on the surface of the two groups in vitro. The effect of RGD on the stability of cell adhesion on the surface of materials at different flow rates. Results the results of in vitro blood compatibility were as follows: the hemolysis rate of the steel sheets in the bare steel sheet and the PEG-PLA-PGL / RGD group was less than 5, and there was no hemolytic effect in the RGD group, and compared with the sample blood, the hemolysis rate of the RGD was lower than that of the PEG-PLA-PGL / RGD group. The APTT of the three groups showed significant difference (P < 0.05), which could improve the blood anticoagulant performance of the samples. The PEG-PLA-PGL coating had no statistical difference compared with the bare steel sheet. The PEG-PLA-PGL / RGD coating was better than bare steel in platelet adsorption and albumin adsorption after graft RGD (P < 0.05), which improved the blood compatibility of bare steel to some extent. The results of cell adhesion stability showed that the PEG-PLA-PGL copolymers were attached to RGD on the surface of the PEG-PLA-PGL copolymers. The residual rate of cells increased significantly (P < 0.05), both in the control group and in the experimental group before the T-type bifurcation was higher than that in the branched and branched cells. Conclusion the PEG-PLA-PGL / RGD coating scaffold was confirmed by in vitro experiments. [WT5 "HZ] [WT5BZ] the results show that the cell residual rate of the PEG-PLA-PGL / RGD coating scaffolds is higher than that of the control group and the experimental group. The material has good blood compatibility. In vitro experiments showed that RGD could improve the cell adhesion stability of PEG-PLA-PGL scaffold, including at the junction of T-tube, but the cell adhesion stability was affected by T-tube bifurcation.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R541.4;R318.08

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本文編號(hào)：1999369