Dataset Information

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(?-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.

SUBMITTER: Campagnolo P

PROVIDER: S-EPMC5405341 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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

Campagnolo Paola P Gormley Adam J AJ Chow Lesley W LW Guex Anne Géraldine AG Parmar Paresh A PA Puetzer Jennifer L JL Steele Joseph A M JA Breant Alexandre A Madeddu Paolo P Stevens Molly M MM

Advanced healthcare materials 20161026 23

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 ...[more]

PMID: 27782370

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Project description:As increasing effort is dedicated to investigating the regenerative capacity of decellularized tissues, research has progressed to recellularizing these tissues prior to implantation. The delivery and support of cells seeded throughout acellular scaffolds are typically conducted through the vascular axis of the tissues. However, it is unclear how cell concentration and injection frequency can affect the distribution of cells throughout the scaffold. Furthermore, what effects re-endothelialization have on vascular patency and function are not well understood. We investigated the use of ultrasound-guided photoacoustic (US/PA) imaging as a technique to visualize the distribution of microvascular endothelial cells within an optimized acellular construct upon re-endothelialization and perfusion conditioning. We also evaluated the vascular performance of the re-endothelialized scaffold using quantitative vascular corrosion casting (qVCC) and whole-blood perfusion. We found US/PA imaging was an effective technique to visualize the distribution of cells. Cellular retention following perfusion conditioning was also detected with US/PA imaging. Finally, we demonstrated that a partial recovery of vascular performance is possible following re-endothelialization-confirmed by fewer extravasations in qVCC and improved blood clearance following whole-blood perfusion.Statement of significanceRe-endothelialization is a method that enables decellularized tissue to become useful as a tissue engineering construct by creating a nutrient delivery and waste removal system for the entire construct. Our approach utilizes a decellularization method that retains the basement ECM of a highly vascularized tissue upon which endothelial cells can be injected to form an endothelium. The US/PA method allows for rapid visualization of cells within a construct several cm thick. This approach can be experimentally used to observe changes in cellular distribution over large intervals of time, to help optimize cell seeding parameters, and to verify cell retention within re-endothelialized constructs. This approach has temporal and depth advantages compared to section reconstruction and imaged fluorophores respectively.

Project description:Vascularization remains a substantial limitation to the viability of engineered tissue. By comparing in vivo vascularization dynamics of a self-assembled prevascular endothelial-fibroblast model to avascular grafts, we explore the vascularization rate limitations in implants at early time intervals, during which tissue hypoxia begins to affect cell viability. Scaffold-free prevascular endothelial-fibroblast constructs (SPECs) may serve as a modular and reshapable vascular bed in replacement tissues. SPECs, fibroblast-only spheroids (FOS), and silicone implants were implanted in 54 Sprague Dawley rats and harvested at 6, 12, and 24?h (n?=?5 per time point and implant type). We hypothesized that the primary endothelial networks of the SPECs allow earlier anastomosis and increased vessel formation in the interior of the implant compared to FOS and silicone implants within a 24?h window. All constructs were encapsulated by an endothelial lining at 6?h postimplantation and SPEC internal cords inosculated with the host vascular network by this time point. SPECs had a significantly higher microvascular area fraction and branch/junction density of penetrating cords at 6-12?h compared with other constructs. In addition, SPECs demonstrated perivascular cell recruitment, lumen formation, and network remodeling consistent with vessel maturation at 12-24?h; however, these implants were poorly perfused within our observation window, suggesting poor lumen patency. FOS vascular characteristics (microvessel area and penetrating cord density) increased within the 12-24?h period to represent those of the SPEC implants, suggesting a 12?h latency in host response to avascular grafts compared to prevascular grafts. Knowledge of this temporal advantage in in vitro prevascular network self-assembly as well as an understanding of the current limitations of SPEC engraftment builds on our theoretical temporal model of tissue graft vascularization and suggests a crucial time window, during which technological improvements and vascular therapy can improve engineered tissue survival.

Dataset Information

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

Publications

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

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