TY - JOUR
T1 - Pericyte Seeded Dual Peptide Scaffold with Improved Endothelialization for Vascular Graft Tissue Engineering
AU - Campagnolo, Paola
AU - Gormley, Adam J.
AU - Chow, Lesley W.
AU - Guex, Anne Géraldine
AU - Parmar, Paresh A.
AU - Puetzer, Jennifer L.
AU - Steele, Joseph A.M.
AU - Breant, Alexandre
AU - Madeddu, Paolo
AU - Stevens, Molly M.
PY - 2016/12/7
Y1 - 2016/12/7
N2 - 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.
AB - 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.
KW - biofunctionalization
KW - electrospinning
KW - endothelialization
KW - pericytes
KW - tissue engineered vascular graft
UR - http://www.scopus.com/inward/record.url?scp=84997498689&partnerID=8YFLogxK
U2 - http://onlinelibrary.wiley.com/doi/10.1002/adhm.201600699/full
DO - http://onlinelibrary.wiley.com/doi/10.1002/adhm.201600699/full
M3 - Article (Academic Journal)
C2 - 27782370
AN - SCOPUS:84997498689
VL - 5
SP - 3046
EP - 3055
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
SN - 2192-2640
IS - 23
ER -