Biofunctionalization of decellularized porcine aortic valve with OPG-loaded PCL nanoparticles for anti-calcification.

Biofunctionalization of decellularized porcine aortic valve with OPG-loaded PCL nanoparticles for anti-calcification.
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负载 OPG 的 PCL 纳米粒子对脱细胞猪主动脉瓣进行生物功能化以抗钙化

DOI:
10.1039/c9ra00408d
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发表时间:
2019-04-12
期刊:
影响因子:
3.9
通讯作者:
--
中科院分区:
化学3区
文献类型:
--
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脱细胞瓣膜支架保持了天然瓣膜的形态结构,具有良好的组织相容性和较低的免疫原性,被广泛应用于组织工程心脏瓣膜。然而,细胞瓣膜表面失去了原来的内皮细胞覆盖物,暴露出胶原蛋白,提前造成瓣膜钙化和腐烂。本研究利用纳米粒给药系统和组织工程技术,将骨保护素(ε)负载的聚己内酯纳米粒桥接到脱细胞瓣膜上,构建了一种新型的具有缓释功能的抗钙化复合瓣。采用乳化溶剂挥发法制备了粒径为133 nm、zeta电位为−27.8 mV的羟基磷灰石纳米粒子。透射电子显微镜观察表明,所制备的纳米粒形状圆整、大小规则、分布均匀,包封率为75%,体外缓释,无猝发释放,对骨髓间充质干细胞无细胞毒性,体外含有OPG纳米粒。骨髓间充质干细胞向成骨细胞分化的时间延迟。纳米颗粒修饰的脱细胞瓣膜保持完好,胶原纤维连续。大鼠皮下植入8周后,瓣膜形态结构基本完整,复合瓣膜具有一定的抗钙化能力。
Decellularized valve stents are widely used in tissue-engineered heart valves because they maintain the morphological structure of natural valves, have good histocompatibility and low immunogenicity. However, the surface of the cell valve loses the original endothelial cell coverage, exposing collagen and causing calcification and decay of the valve in advance. In this study, poly ε-caprolactone (PCL) nanoparticles loaded with osteoprotegerin (OPG) were bridged to a decellularized valve using a nanoparticle drug delivery system and tissue engineering technology to construct a new anti-calcification composite valve with sustained release function. The PCL nanoparticles loaded with OPG were prepared via an emulsion solvent evaporation method, which had a particle size of 133 nm and zeta potential of −27.8 mV. Transmission electron microscopy demonstrated that the prepared nanoparticles were round in shape, regular in size, and uniformly distributed, with an encapsulation efficiency of 75%, slow release in vitro, no burst release, no cytotoxicity to BMSCs, and contained OPG nanoparticles in vitro. There was a delay in the differentiation of BMSCs into osteoblasts. The decellularized valve modified by nanoparticles remained intact and its collagen fibers were continuous. After 8 weeks of subcutaneous implantation in rats, the morphological structure of the valve was almost complete, and the composite valve showed anti-calcification ability to a certain extent.
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