Oriented <scp>PLA</scp> @ <scp>TP</scp> @ <scp>CuS</scp> Piezoelectric Nanofibers for the Regulation of Endothelial Cell Behavior and Thrombolysis

ABSTRACT The long‐term patency of small‐diameter in situ tissue‐engineered blood vessels is often compromised by insufficient endothelialization and thrombosis. To address these challenges, we developed oriented polylactic acid@tea polyphenol@copper sulfide ((O)PLA@TP@CuS) nanofibers that synergistically integrate piezoelectric stimulation for endothelialization, antioxidant protection, and combined photothermal–sonodynamic thrombolysis. The nanofibers, fabricated with PLA:TP ratios of 70:30 and 80:20, exhibited excellent cytocompatibility and generated output voltages of 0.190 and 0.310 V, respectively, owing to the intrinsic piezoelectricity of PLA. Under 0.8 W/cm 2 ultrasound, the (O)PLA@TP@CuS (80:20) group achieved the highest Optical Density (OD) value (1.15) and a 167.3% increase in human umbilical vein endothelial cell (HUVEC) viability, confirming that enhanced piezoelectric responsiveness favored HUVEC adhesion and proliferation. Additionally, the intrinsic radical‐scavenging activity of TP significantly reduced O 2 − and OH − levels, alleviating Reactive Oxygen Species (ROS)‐induced damage during photothermal and ultrasound treatments and thereby improving biosafety. Leveraging both the photothermal conversion of CuS and piezoelectric properties of PLA, the (O)PLA@TP@CuS (80:20) nanofibers achieved a thrombus dissolution rate of 0.81, representing a 78% improvement through synergistic photothermal–sonodynamic therapy. Collectively, these findings demonstrate that (O)PLA@TP@CuS nanofibers not only promote HUVEC proliferation and alignment via piezoelectric stimulation but also enhance thrombolysis while mitigating oxidative stress, offering a promising strategy to improve the long‐term patency of small‐diameter tissue‐engineered blood vessels.