applications is presented. This scaffold incorporates two tethered peptides: the derived peptide (Adh) on the side and a heparin-binding peptide (Hep) on the ‘luminal’ side. Additionally, the side of the scaffold is seeded with saphenous ‘abluminal’ ‘abluminal’ 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 side of the scaffold further increase ‘abluminal’/Hep 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. 1. Introduction According to the World Health Organization, coronary artery disease is the leading cause of death and disability in the world. Autologous vascular bypass is a common intervention aimed at re-establishing blood flow to the cardiac tissue in patients for whom balloon angioplasty and/or stenting are not viable options. However, in patients with vascular complications or requiring multiple bypasses, autologous vessels might not be available or sufficiently healthy. Tissue engineered vascular grafts (TEVGs) are an attractive alternative to natural vessels. In recent years, many different approaches have been tested both in vitro and to implement the design of new TEVG, in particular of small diameter vessels in vivo below the critical diameter of 6 mm (for reviews see [1,2]). In these approaches, cells are seeded on biodegradable vascular scaffolds prepared with a variety of techniques, including hydrogel self-assembly, particulate-leaching, and electrospinning. In particular,
applications is presented. This scaffold incorporates two tethered peptides: the 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. 1. Introduction According to the World Health Organization, coronary artery disease is the leading cause of death and disability in the world. Autologous vascular bypass is a common intervention aimed at re-establishing blood flow to the cardiac tissue in patients for whom balloon angioplasty and/or stenting are not viable options. However, in patients with vascular complications or requiring multiple bypasses, autologous vessels might not be available or sufficiently healthy. Tissue engineered vascular grafts (TEVGs) are an attractive alternative to natural vessels. In recent years, many different approaches have been tested both in vitro and in vivo to implement the design of new TEVG, in particular of small diameter vessels below the critical diameter of 6 mm (for reviews see [1,2]). In these approaches, cells are seeded on biodegradable vascular scaffolds prepared with a variety of techniques, including hydrogel self-assembly, particulate-leaching, and electrospinning. In particular, derived
CampagnoloP-AdvHealthcareMater-2016-accepted-version.docx