title: Pericyte Seeded Dual Peptide Scaffold with Improved Endothelialization for Vascular Graft Tissue Engineering.
abstract: The development of synthetic vascular grafts for coronary artery bypass is challenged by insufficient endothelialization, which increases the risk of thrombosis, and the lack of native cellular constituents, which favors pathological remodeling. Here, a bifunctional electrospun poly(ε-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 proangiogenic growth factors. The Adh peptide significantly increases endothelial cell adhesion, while the Hep peptide promotes accumulation of vascular endothelial growth factor 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 increases endothelial cell density, indicating a combinatory effect of the peptides and pericytes. Finally, 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.
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.
authors: Paola
authors: P
authors: Campagnolo
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.
authors: Adam J
authors: AJ
authors: Gormley
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.
authors: Lesley W
authors: LW
authors: Chow
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.|National Heart and Lung Institute, Imperial College London, 435 Du Cane Road, W12 0NN, London, UK.
authors: Anne Géraldine
authors: AG
authors: Guex
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.
authors: Paresh A
authors: PA
authors: Parmar
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.
authors: Jennifer L
authors: JL
authors: Puetzer
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.
authors: Joseph A M
authors: JA
authors: Steele
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.
authors: Alexandre
authors: A
authors: Breant
authors: Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Upper Maudlin St, BS2 8HW, Bristol, UK.
authors: Paolo
authors: P
authors: Madeddu
authors: Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Royal School of Mines, Imperial College London, Prince Consort Rd, SW7 2AZ, London, UK.
authors: Molly M
authors: MM
authors: Stevens
mesh_terms: D001807:Blood Vessel Prosthesis; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D053495:Osteopontin / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D010455:Peptides; D011091:Polyesters; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; C016240:polycaprolactone; D006493:Heparin
keywords: biofunctionalization; electrospinning; endothelialization; pericytes; tissue engineered vascular graft