Pericyte Seeded Dual Peptide Scaffold with Improved Endothelialization for Vascular Graft Tissue Engineering

The development of synthetic vascular grafts for coronary artery bypass is challenged by insufficient endothelialization, which exposes to the risk of thrombosis, and lack of native cellular constituents, which favours pathological remodelling. Here, an bifunctional electrospun poly(e-caprolactone) (PCL) scaffold with potential for synthetic vascular graft applications is presented. This scaffold incorporates two tethered peptides: the osteopontin-derived peptide (Adh) on the ‘luminal’ side and a heparin-binding peptide (Hep) on the ‘abluminal’ side. Additionally, the ‘abluminal’ side of the scaffold is seeded with saphenous vein-derived pericytes (SVPs) as a source of pro-angiogenic growth factors. The Adh peptide significantly increase endothelial cell adhesion, while the Hep peptide promote accumulation of vascular endothelial growth factor (VEGF) secreted by SVPs. SVPs increase endothelial migration both in a transwell assay and a modified scratch assay performed on the PCL scaffold. Seeding of SVPs on the ‘abluminal’/Hep side of the scaffold further increase endothelial cell density, indicating a combinatory effect of the peptides and pericytes. Lastly, SVP-seeded scaffolds are preserved by freezing in a xeno-free medium, maintaining good cell viability and function. In conclusion, this engineered scaffold combines patient-derived pericytes and spatially organized functionalities, which synergistically increase endothelial cell density and growth factor retention.