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Abstract: The high incidence of cardiovascular disease has led to significant demand for synthetic vascular grafts in clinical applications. Anti-proliferation drugs are usually loaded into devices to achieve desirable anti-thrombosis effects after implantation. However, the non-selectiveness of these conventional drugs can lead to the failure of blood vessel reconstruction, leading to potential complications in the long term. To address this issue, an asymmetric membrane was constructed through electro-spinning techniques. The bilayer membrane loaded and effectively released nitric oxide (NO), as hoped, from only one side. Due to the short diffusion distance of NO, it exerted negligible effects on the other side of the membrane, thus allowing selective regulation of different cells on both sides. The released NO boosted the growth of endothelial cells (ECs) over smooth muscle cells (SMCs)�while on the side where NO was absent, SMCs grew into multilayers. The overall structure resembled a native blood vessel, with confluent ECs as the inner layer and layers of SMCs to support it. In addition, the membrane preserved the normal function of ECs, and at the same time did not exacerbate inflammatory responses. By preparing this material type that regulates cell behavior differentially, we describe a new method for its application in the cardiovascular field such as for artificial blood vessels.

浙江大学计剑等 | 具有差异性调控多细胞行为的非对称载药双层电纺纤维膜用于人工血管的构建

本研究论文聚焦差异调节细胞行为的材料制备方法用于人工血管构建。心血管疾病（CVD）较高发病率导致临床上对人工血管有着巨大的需求。人工血管在植入后，通常连用抗增殖药物以实现抗血栓等目的。然而，常规药物的非选择性细胞抑制作用往往阻碍血管重建过程，增加潜在并发症的风险。针对这一问题，本课题通过静电纺丝技术构建了非对称载药双层膜。双层膜一侧加载N-乙酰-S-亚硝基-D-青霉胺，从而有效释放NO。由于NO的扩散距离短，它对膜的另一侧的影响可以忽略不计，从而可以选择性地调节两侧的不同细胞。释放的NO增强了血管内皮细胞(EC)对平滑肌细胞(SMC)的竞争性生长。而在没有NO载药的一侧，SMC则能够成长为多层结构。这一不对称性能够诱导生成类似天然血管的结构，在保留了EC的正常功能的同时，不引起强烈的炎症反应。这种差异调节细胞行为的材料制备方法，有望为人工血管构建等应用提供新的启示。