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载 VEGF 的 PCL-mPEG 和载 PDGF 的 PCL-壳聚糖双层血管移植物的理化性质、体外和体内评价。

Physicochemical, in vitro and in vivo evaluation of VEGF loaded PCL-mPEG and PDGF loaded PCL-Chitosan dual layered vascular grafts.

机构信息

Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.

Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, South Korea.

出版信息

J Biomed Mater Res B Appl Biomater. 2024 Jan;112(1):e35325. doi: 10.1002/jbm.b.35325. Epub 2023 Sep 7.

DOI:10.1002/jbm.b.35325
PMID:37675952
Abstract

The present study has attempted to evaluate the endothelialization and smooth muscle regeneration efficiency of a novel dual-layer small-diameter vascular graft. Two types of layers (PCL-mPEG-VEGF and PCL-Chitosan-PDGF) were fabricated to find out the best layer giving endothelialization support for the lumen and unique contractile function for outer layer of blood vessels. Platelet-derived growth factor (PDGF) and chitosan were immobilized onto PCL surface by aminolysis-based surface modification technique. Besides, Poly (ethylene glycol) methyl ether (mPEG) and vascular endothelial growth factor (VEGF) were directly blended with PCL. Morphological analysis of membranes ensured consistency of average fibers diameter with native extracellular matrix. A favorable interaction of PCL-mPEG-VEGF with cow pulmonary endothelial cells (CPAEs) and PCL-Chitosan-PDGF with rat bone marrow mesenchymal stem cells (RBMSCs) was obtained during in vitro study. Controlled growth factor release patterns were found from both layers. Further, PCL-mPEG-VEGF exhibited endothelial markers expression properties from RBMSCs. Up-regulation of SMCs markers expression was significantly ensured by the PCL-Chitosan-PDGF membrane. Thus, PCL-mPEG-VEGF and PCL-Chitosan-PDGF were preferred as inner and outer layers respectively of a finally prepared tubular hybrid tissue engineered small diameter vascular graft. Finally, the dual-layer vascular graft was implanted onto a rat abdominal aorta model for 2 months. The extracted samples exhibited the presence of endothelial marker (ICAM 1) in the inner layer and smooth muscle cell marker (αSMA) in the outer layer as well as substantial amount of collagen deposition was observed in the both layers.

摘要

本研究试图评估一种新型双层小直径血管移植物的内皮化和平滑肌再生效率。制备了两种类型的层(PCL-mPEG-VEGF 和 PCL-壳聚糖-PDGF),以找出最佳的层,为内腔提供内皮化支持,为血管的外层提供独特的收缩功能。血小板衍生生长因子(PDGF)和壳聚糖通过基于氨解的表面改性技术固定在 PCL 表面上。此外,聚乙二醇甲基醚(mPEG)和血管内皮生长因子(VEGF)直接与 PCL 共混。膜的形态分析确保了平均纤维直径与天然细胞外基质的一致性。体外研究表明,PCL-mPEG-VEGF 与牛肺内皮细胞(CPAEs)具有良好的相互作用,PCL-Chitosan-PDGF 与大鼠骨髓间充质干细胞(RBMSCs)具有良好的相互作用。从两个层面都发现了控制生长因子释放模式。此外,PCL-mPEG-VEGF 从 RBMSCs 中表现出内皮标志物的表达特性。PCL-Chitosan-PDGF 膜显著确保了 SMCs 标志物表达的上调。因此,PCL-mPEG-VEGF 和 PCL-Chitosan-PDGF 分别被优选为最终制备的管状混合组织工程小直径血管移植物的内层和外层。最后,双层血管移植物被植入大鼠腹主动脉模型 2 个月。提取的样本在内层显示出内皮标志物(ICAM 1)的存在,在外层显示出平滑肌细胞标志物(αSMA)的存在,并且在两个层中都观察到大量的胶原沉积。

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