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载有 VEGF 的纳米颗粒对脱细胞猪主动脉瓣的表面生物功能化,以加速内皮化。

Surface biofunctionalization of the decellularized porcine aortic valve with VEGF-loaded nanoparticles for accelerating endothelialization.

机构信息

Department of cardiovascular surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, China.

Department of gastroenterology, the Second Affiliated Hospital of Nanchang University, Nanchang, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Apr;97:632-643. doi: 10.1016/j.msec.2018.12.079. Epub 2018 Dec 26.

DOI:10.1016/j.msec.2018.12.079
PMID:30678950
Abstract

The original intention for building a tissue-engineered heart valve (TEHV) was to simulate a normal heart valve and overcome the insufficiency of the commonly used heart valve replacement in the clinic. The endothelialization of the TEHV is very important as the endothelialized TEHV can decrease platelet adhesion and delay the valvular calcification decline process. In this work, we encapsulated vascular endothelial growth factor (VEGF) into polycaprolactone (PCL) nanoparticles. Then, through the Michael addition reaction, PCL nanoparticles were introduced onto the decellularized aortic valve to prepare a hybrid valve. The encapsulation efficiency of the PCL nanoparticles for VEGF was up to 82%, and the in vitro accumulated release rate was slow without an evident initial burst release. In addition, the hybrid valve had a decreased hemolysis ratio and possessed antiplatelet adhesion capacity, and it was able to promote the adhesion and proliferation of endothelial cells, covering the surface with a dense cell layer to accelerate endothelialization. An experiment involving the subcutaneous implant in SD rats showed that at week 8, lots of blood capillaries were formed in the hybrid valve. Mechanics performance testing indicated that the mechanical property of the hybrid valve was partly improved. Taken together, we applied a nano-drug controlled release system to fabricate TEHV, and provide an approach for the biofunctionalization of the TEHV scaffold for accelerating endothelialization.

摘要

构建组织工程心脏瓣膜(TEHV)的初衷是模拟正常心脏瓣膜,并克服临床常用心脏瓣膜置换的不足。TEHV 的内皮化非常重要,因为内皮化的 TEHV 可以减少血小板黏附,延缓瓣膜钙化下降过程。在这项工作中,我们将血管内皮生长因子(VEGF)包封到聚己内酯(PCL)纳米颗粒中。然后,通过迈克尔加成反应,将 PCL 纳米颗粒引入脱细胞主动脉瓣中,制备混合瓣膜。PCL 纳米颗粒对 VEGF 的包封效率高达 82%,并且体外累积释放率较慢,没有明显的初始突释。此外,混合瓣膜的溶血比例降低,具有抗血小板黏附能力,能够促进内皮细胞的黏附和增殖,在表面形成密集的细胞层,加速内皮化。一项涉及 SD 大鼠皮下植入的实验表明,在第 8 周时,混合瓣膜中形成了大量的毛细血管。力学性能测试表明,混合瓣膜的力学性能得到了一定程度的改善。总之,我们应用纳米药物控释系统来构建 TEHV,并为加速内皮化的 TEHV 支架的生物功能化提供了一种方法。

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