Designing Cardiovascular Implants Taking in View the Endothelial Basement Membrane

Abstract

Insufficient endothelialization of cardiovascular grafts is a major hurdle in vascular surgery and regenerative medicine, bearing a risk for early graft thrombosis. Neither of the numerous strategies pursued to solve these problems were conclusive. Endothelialization is regulated by the endothelial basement membrane (EBM), a highly specialized part of the vascular extracellular matrix. Thus, a detailed understanding of the structure–function interrelations of the EBM components is fundamental for designing biomimetic materials aiming to mimic EBM functions. In this review, a detailed description of the structure and functions of the EBM are provided, including the luminal and abluminal interactions with adjacent cell types, such as vascular smooth muscle cells. Moreover, in vivo as well as in vitro strategies to build or renew EBM are summarized and critically discussed. The spectrum of methods includes vessel decellularization and implant biofunctionalization strategies as well as tissue engineering-based approaches and bioprinting. Finally, the limitations of these methods are highlighted, and future directions are suggested to help improve future design strategies for EBM-inspired materials in the cardiovascular field.

Vascular tissue engineering from human adipose tissue: fundamental phenotype of its resident microvascular endothelial cells and stromal/stem cells

“…2 ). These findings are in accordance with the current understanding of endothelial basement membrane biology [ 39 , 40 ], adding further support to the emergent role for mural cells in its assembly [41] .…”

“…Matrigel®, Corning and Cultrex TM , Bio-Techne) reflects that of the endothelial basement membrane, which normally separates ECs from underlying mural cells (i.e. pericytes and vascular smooth muscle cells) [ 39 , 40 ]. Accordingly, the self-assembly of ASCs in gelled basement membrane extract may in fact be a manifestation of their perivascular phenotype, recapitulating their predisposition to assume an abluminal localization to the endothelial basement membrane.…”

“…The endothelial basement membrane is critical to the stabilization and maturation of the endothelium [ 39 , 40 ]. Merely 20–200 nm thick, this specialized extracellular matrix upon which the endothelium resides is composed of laminin, collagen IV, nidogen, and heparin sulfate proteoglycans such as perlecan and agrin [ 39 , 40 ].…”

“…The endothelial basement membrane is critical to the stabilization and maturation of the endothelium [ 39 , 40 ]. Merely 20–200 nm thick, this specialized extracellular matrix upon which the endothelium resides is composed of laminin, collagen IV, nidogen, and heparin sulfate proteoglycans such as perlecan and agrin [ 39 , 40 ]. While these basement membrane constituents are predominantly produced by HAMVECs, our findings suggest that ASCs may contribute to the assembly of the basement membrane, at least in part, through their deposition of certain laminins and collagen IV ( Fig.…”

KANK4 Promotes Arteriogenesis by Potentiating VEGFR2 Signaling in a TALIN-1–Dependent Manner

“…Moreover, we did not detect KANK4 expression in commercially acquired HUAECs and human aorta ECs (Figure S7B) because those cells were expanded for several passages before cryopreservation and shipping. However, a previous study demonstrated that cultured HUVECs and HUAECs behave similarly regarding cell proliferation, metabolic activity, ECM production, and other cardiovascular-associated functions 43 and the quick loss of KANK4 expression in ECs after isolation. Therefore, we investigated KANK4 function in vitro by directly overexpressing KANK4 in HUVECs.…”