Plasma-activated electrospun scaffolds for enhanced endothelialization in vascular tissue engineering

Abstract Scaffold-based tissue engineering (TE) offers promising strategies for repairing damaged tissues, yet insufficient in vivo vascularization remains a major limitation, as adequate blood vessel formation is essential for long-term cell survival and function. To overcome this, scaffolds must effectively promote endothelialization by providing suitable topographical and biochemical cues that support the formation of a continuous endothelial cell (EC) monolayer resembling native endothelium. Electrospinning enables the fabrication of extracellular matrix-like nanofibrous (NF) structures that enhance cell attachment, spreading, and proliferation. Although polycaprolactone (PCL) is widely used for its mechanical stability and processability, its hydrophobic surface restricts protein adsorption and efficient cell anchorage. Non-thermal plasma treatment can introduce polar functional groups, increasing hydrophilicity and cytocompatibility without damaging nanofiber morphology. In this study, electrospun PCL NFs were treated with medium-pressure argon plasma to improve their suitability for vascular TE applications. A range of surface characterization techniques was used to assess morphology, chemistry, and wettability. Plasma exposure increased surface oxygen content and transformed the nanofibers from hydrophobic to strongly hydrophilic while preserving structural and mechanical integrity. These surface modifications significantly enhanced EA.hy926 endothelial cell adhesion, spreading, and proliferation. Overall, plasma-activated electrospun scaffolds combined with hiPSC-derived ECs provide a robust foundation for developing functional and clinically relevant endothelialized constructs for vascular tissue engineering. immunofluorescence images of EA.hy926For image description, please refer to the figure legend and surrounding text. SEM images of EA.hy926 cells on fibersFor image description, please refer to the figure legend and surrounding text.