Amphiphilic methoxy polyethyleneglycol-polycaprolactone (mPEG-PCL) block copolymer is widely used in the biomedical field for drug delivery or tissue engineering. At all events, mPEG-PCL copolymers in vivo applications would enter the blood circulation inevitably and contact with blood and vascular endothelial cells. However, previous studies on the hemocompatibility of biomedical polymers have only focused on the direct impact on blood components, ignoring the indirect impact on coagulation function mediated by the interaction between polymers and vascular endothelial cells. Hence, the influence of two mPEG-PCL copolymers (mPEG2k-PCL2k and mPEG5k-PCL2k) with different hydrophilic/hydrophobic ratio on human umbilical vein endothelial cells (HUVECs) and their mediated indirect impact on blood coagulation function were studied. The result showed that both mPEG-PCL copolymers displayed HUVECs proliferation suppression and increased NO release in a concentration-dependent manner. It was further confirmed by cellular uptake, cell cycle, and apoptosis measurement and found that mPEG-PCL copolymers could be endocytosed by HUVECs and significantly blocked DNA replication in G1 phase, but didn't cause obvious apoptosis. In comparison, mPEG2k-PCL2k had more impact on HUVECs than mPEG5k-PCL2k, attributing to the higher endocytosis efficiency of mPEG2k-PCL2k with higher hydrophobicity. Moreover, RT-PCR results of coagulation regulators and TEG measurements in human blood confirmed that mPEG-PCL induced HUVECs to downregulate the expression of anticoagulant factors and upregulate the expression of coagulation factors, thus accelerating blood coagulation and predicting thrombotic risk. This study provides new insights into the blood compatibility of polymeric carriers from the perspective of the vascular endothelium-mediated indirect effect of polymer on blood coagulation function.

两亲性甲氧基聚乙二醇-聚己内酯（mPEG-PCL）嵌段共聚物广泛用于生物医学领域，用于药物输送或组织工程。无论如何，体内mPEG-PCL共聚物应用将不可避免地进入血液循环并与血液和血管内皮细胞接触。然而，先前关于生物医学聚合物的血液相容性的研究仅集中在对血液成分的直接影响上，而忽略了由聚合物与血管内皮细胞之间的相互作用介导的对凝血功能的间接影响。因此，研究了两种亲水/疏水比不同的mPEG-PCL共聚物（mPEG2k-PCL2k和mPEG5k-PCL2k）对人脐静脉内皮细胞（HUVEC）的影响及其对血液凝固功能的间接影响。结果表明，两种mPEG-PCL共聚物均显示HUVEC增殖抑制作用，并以浓度依赖性方式增加NO的释放。细胞摄取，细胞周期，并检测凋亡，发现mPEG-PCL共聚物可被HUVEC内吞并显着阻断G1期的DNA复制，但并未引起明显的凋亡。相比之下，mPEG2k-PCL2k对HUVEC的影响要大于mPEG5k-PCL2k，这归因于mPEG2k-PCL2k的内吞效率更高，且疏水性更高。此外，人体血液中凝血调节剂的RT-PCR结果和TEG测量结果证实，mPEG-PCL诱导HUVEC下调抗凝血因子的表达并上调凝血因子的表达，从而加速血液凝固并预测血栓形成的风险。这项研究从血管内皮介导的聚合物对凝血功能的间接作用的角度为聚合物载体的血液相容性提供了新的见解。