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肝素化PCL/PLGA降解支架远期体内特性

Investigation of long-term results of heparinized polycaprolactone/poly D, L-lactic-glycolic acid scaffold in vivo

摘要:

目的 研究肝素化的聚己内酯(Polycaprolactone,PCL)/聚乳酸乙醇酸(Poly D,L-lactic-glycolic acid,PLGA)双层降解支架体内远期结构稳定性及开放性.方法 建立小型猪急性心肌梗死模型,设立空白支架对照组(BS组)、空白支架+骨髓间充质干细胞移植(MSCs)组(BS-MSCs组)、肝素化支架(HS)+骨髓间充质干细胞移植组(HS-MSCs组).甲苯胺蓝分光光度法绘制支架内肝素体外释放曲线,6个月后连续切片结合3D-DOCTOR软件重建支架管腔轮廓,扫描电镜评价支架内皮化,组织学染色观察支架周围血管新生及支架降解后胶原纤维重塑情况,Western印迹法量化支架内皮细胞环氧合酶(Cyclooxygenase,COX-1/COX-2)和前列腺素合成酶(Prostacyclin Synthase,PGIS)的表达情况,ELISA法量化血浆前列腺素(Prostacyclin,PGI2)和血栓素(Thromboxane,TXA2)的含量.结果 4周时支架内约89%的肝素释放,6周时完全释放.6个月时三维重建显示支架轮廓清晰,无明显变形,管腔被内皮细胞覆盖,周围见大量存活心肌及新生血管,支架降解后空间被新生胶原纤维重塑.HS-MSCs组和BS-MSCs组PGIS的表达及血浆PGI2含量较BS组显著增加(P<0.01和P<0.05);HS-MSCs组COX-1的表达及TXA2的含量较BS-MSCs组、BS组显著减少(P<0.01),后两组间差异无统计学意义(P>0.05).结论 6个月后支架轮扇无明显变形,管腔被内皮细胞覆盖,通过PGI2表达,保证支架的内源性抗凝活性.

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abstracts:

Objective Biodegradable polycaprolactone (PCL)/poly D,L-lactic/glycolic acid (PLGA) scaffold is a promising modality for diffuse coronary atherosclerosis diseases unavailable to bypass graft.The purpose of this study was to evaluate the long-term performance of PCL/PLGA scaffold in vivo following polymer degradation.Methods Two scaffolds with and without heparin modification [Heparinized Scaffold (HS) and Blank Scaffold (BS)] were implanted.Except for control group,bone marrow mesenchymal stem cells (MSCs) were also transplanted around the scaffold.Animals were grouped into control BS group,BS-MSCs group and HS-MSCs group (each n =6) and survived 6 months.Patency and integrity of scaffold were evaluated by echocardiography and 3D-DOCTOR software.Endothelium coverage of the lumen was evaluated by scanning electron microscopy.Neovessles and collagen fiber within the scaffold were identified by histological staining.Prostacyclin (PGI2) and thromboxane (TXA2) production in the plasma were measured by ELISA.The expression of cyclooxygenase (COX-1,COX-2) and prostacyclin synthase PGIS was detected by Western blot.Results The heparinized scaffold kept patent up to 6 months and the lumen was covered by confluent endothelial cells.Histological staining revealed remodeling of collagen fiber and reconstruction of neovascular network immediately around the lumen.PGI2 production and PGIS expression in BSMSCs group and HS-MSCs group significantly increased compared with BS group (P < 0.05 and P < 0.01,respectively).Nonetheless,TXA2 production and COX-1 expression in BS-MSCs group was more pronounced than HS-MSCs group (P < 0.01),showing no difference between BS-MSCs and BS group (P > 0.05).Conclusion Despite polymer degradation and entire heparin release,the scaffold could continuously keep the structual integrity and lumen patency until 6 months by reinforcement of host collagen fiber and PGI2 expression.

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作者: 赵健 [1] 程兆云 [1] 权晓强 [1] 赵子牛 [1] 吕丰 [2] 刘晓程 [3]
作者单位: 450003,河南省人民医院 郑州大学人民医院心血管外科 [1] 天津生物医学工程研究所生物材料重点实验室 [2] 天津泰达国际心血管病医院 [3]
期刊: 《中华胸心血管外科杂志》2013年29卷10期 620-623页 ISTICPKUCSCD
栏目名称: 实验研究
DOI: 10.3760/cma.j.issn.1001-4497.2013.10.013
发布时间: 2013-12-03
基金项目:
河南省科技厅重点科技攻关项目 天津市科技发展计划项目
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