hiPSC-derived endothelial progenitor cells seeded on aligned electrospun nanofibers promote endothelialization of biomimetic small-diameter vascular grafts in vitro.

Cardiovascular disease remains the predominant cause of mortality globally. Vascular grafts serve as substitutes to restore blood flow by replacing or bypassing diseased or occluded blood vessels. The application of small-diameter vascular grafts (SDVGs, diameter ≤ 6 mm) is limited due to their poor long-term patency primarily caused by acute thrombosis and chronic neointimal hyperplasia after implantation. Seeding cells to simulate the structure and function of the native endothelium represents an effective strategy to improve long-term patency. However, the effect of endothelialization has been constrained by the limited availability and functional heterogeneity of endogenous endothelial progenitor cells (EPCs), as well as the lack of biomimetic cellular organization on graft surfaces. In this study, we differentiated human induced pluripotent stem cells (hiPSCs) into EPCs (hiPSC-EPCs), which exhibited excellent pro-angiogenic function and the potential to inhibit inflammation. To promote biomimetic endothelialization, hiPSC-EPCs were seeded onto aligned electrospun nanofibers (ESNFs) fabricated for SDVGs. The aligned ESNFs guided hiPSC-EPCs to adopt a spindle-shaped morphology and an oriented cellular arrangement. Furthermore, the aligned hiPSC-EPC layer reduced platelet adhesion and inflammatory factor expression, while promoting the expression of endothelial functional markers in vitro. Our study combines hiPSC-EPCs with aligned ESNFs to closely simulate the structure and function of the native endothelium, thereby demonstrating a promising strategy to develop biomimetic SDVGs for clinical applications.