Vascular endothelial cells mediated the indirect effect of mPEG-PCL copolymers on blood coagulation

Abstract

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.