Applying elastic fibre biology in vascular tissue engineering

Abstract

For the treatment of vascular disease, the major cause of death in Western society, there is an urgent need for tissue-engineered, biocompatible, small calibre artery substitutes that restore biological function. Vascular tissue engineering of such grafts involves the development of compliant synthetic or biomaterial scaffolds that incorporate vascular cells and extracellular matrix. Elastic fibres are major structural elements of arterial walls that can enhance vascular graft design and patency. In blood vessels, they endow vessels with the critical property of elastic recoil. They also influence vascular cell behaviour through direct interactions and by regulating growth factor activation. This review addresses physiological elastic fibre assembly and contributions to vessel structure and function, and how elastic fibre biology is now being exploited in small diameter vascular graft design.

Cell Adhesion to Tropoelastin Is Mediated via the C-terminal GRKRK Motif and Integrin αVβ3

“…More recent data has shown that human umbilical vein endothelial cells can adhere to recombinant fragments of human tropoelastin (30,31). In contrast to other data, regions encoded by the N-terminal exons (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), the central exons (18 -27), and the C-terminal exons (18 -36) all supported human umbilical vein endothelial cell attachment.…”

“…Although integrin ␣ V ␤ 3 has been shown to interact directly with tropoelastin by solid phase analysis, the utilization of this integrin by cells adhering to human tropoelastin has not been studied. As tropoelastin is the major constituent of elastic tissue and in vivo elastic fibers are associated with cells (30,34), we have investigated the cell binding properties of human tropoelastin.…”

Expression of Versican Isoform V3 in the Absence of Ascorbate Improves Elastogenesis in Engineered Vascular Constructs

“…6 Since elastic fibers are critical to the performance of native blood vessels, there is substantial interest in developing TEBVs enriched in elastin. 5,[7][8][9] Notably, elastin synthesis is prominent in late fetal and perinatal vasculature; however, adult ASMCs synthesize little or no elastin either in vivo or in vitro. 10,11 Consequently, a major deficiency in TEBVs that incorporate adult ASMCs is the lack of functional elastic fibers and lamellae, [12][13][14] which can lead to mechanical failure.…”

“…4 The elastic fibers are arranged in concentric, fenestrated lamellae in the media of the vessel wall. 5 In addition to its mechanical contribution, elastin regulates ASMC growth-elastin knockout mice die from vascular stenosis as a consequence of excessive ASMC proliferation and synthesis of an occlusive neointimal matrix. 6 Since elastic fibers are critical to the performance of native blood vessels, there is substantial interest in developing TEBVs enriched in elastin.…”

Tissue Engineering and Regenerative Strategies to Replicate Biocomplexity of Vascular Elastic Matrix Assembly

“…This process involves several steps of coordinated intracellular and extracellular activities directed by vascular smooth muscle cells (VSMCs) and has been described in more detail elsewhere. 7,8 Broadly, the elastin protein is secreted by VSMCs as the tropoelastin precursor molecule into the extracellular space. There, the tropoelastin precursors bind with the elastin binding protein (EBP), a chaperone that protects them from degradation, via their hydrophobic amino acid sequence VGVAPG.…”