Characterization of Endothelial Basement Membrane Nanotopography in Rhesus Macaque as a Guide for Vessel Tissue Engineering

Abstract

Basement membranes have many features that greatly influence vascular endothelial cell function, including a complex three-dimensional topography. As a first step in the design and development of vascular prosthetics, we undertook a thorough characterization of the topographic features of endothelial vascular basement membranes utilizing transmission electron microscopy and scanning electron microscopy. Specifically, we quantitatively analyzed the topographic features present in the aorta, carotid, saphenous, and inferior vena cava vessels in the rhesus macaque. Our results indicate that vascular basement membranes are composed of a complex meshwork consisting of pores and fibers in the submicron (100-1000 nm) and nanoscale (1-100 nm) range, consistent with what has previously been reported in basement membranes of other tissues. We found significant differences ( p < 0.05) in basement membrane thickness and pore and fiber diameter depending on the location and physical properties of the vessel. These results have relevance to our fundamental understanding of vascular endothelial cell-matrix interactions in health and disease, evolving strategies in cell and tissue engineering and the design of cardiovascular prosthetic devices.

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

“…Vascular endothelial cells are supported by their underlying basement membrane which plays major roles in their normal function. Alterations in different characteristics of such extracellular environment including its stiffness have been observed in the case of some vascular diseases (Baluk et al 2003;Liliensiek et al 2009;Stroka & Aranda-Espinoza 2011a;Yeh et al 2012). Such changes in the stiffness of the underlying substrate of endothelial cells can affect their function.…”

Topography Design Concept of a Tissue Engineering Scaffold for Controlling Cell Function and Fate Through Actin Cytoskeletal Modulation

“…(Adapted with permission from Nikkhah et al 19 Copyright 2010 by Elsevier, Inc.) Color images available online at www .liebertpub.com/teb surface and form a relatively planar interface with ECM. Cells on a dense layer of a 2D basement membrane 65,66 and on mineralized bone or teeth are under a similar constraint.…”

Topographic cell instructive patterns to control cell adhesion, polarization and migration

“…Biological tissues display a vast variety of topographies such as fibrils, fibre bundles, pits and protrusions, whose characteristic dimensions span from tens of nanometres up to the micrometre scale [1][2][3]. It is therefore reasonable to expect that the presentation of topographic signals is one of the strategies that Nature adopts to impart to cells specific orders, which eventually dictate their behaviour.…”