Abstract

Coronary bypass is the most common intervention for coronary obstruction. When autologous vessels are unavailable, synthetic grafts are employed. The challenge of rapid endothelialisation to reduce complications is still far from being achieved. This study describes a novel approach to synthetic graft design, based on the spatially defined presentation of functionalities within the scaffold, contributing to the biological activity of the pre-seeded pro-angiogenic human saphenous vein-derived pericytes (SVP). Indeed, the electrospun polycaprolactone (PCL) presented two distinct functionalities on either side: the osteopontin-derived adhesion peptide (Adh) to facilitate endothelial adhesion on the luminal side and the heparin binding peptide (Hep) to create a reservoir of SVP-produced growth factors on the adventitial side. Conjugated peptides retained functionality within the scaffold, with Adh increasing endothelial cells (EC) adhesion and Hep binding the SVP-produced VEGF and releasing it to improve EC growth over time. Additionally, seeding of the scaffold with SVP increased EC migration and proliferation, suggesting their supporting role in re-endothelialisation of the graft. When seeded on the dual peptide scaffold, SVP acted synergistically with the peptides determining a greater EC coverage, as compared to each component alone. SVP-seeded scaffolds were cryopreserved for up to 2 weeks in GMP-grade medium preserving cell viability and functionality. In conclusion, we engineered a progenitor cell-seeded vascular graft, which incorporates spatially organised biomolecules that act synergistically with the cells to support EC coverage.