Endothelialization mechanisms in vascular grafts

Abstract

Despite the wide variety of tissue-engineered vascular grafts that are currently being developed, autologous vessels, such as the saphenous vein, are still the gold standard grafts for surgical treatment of vascular disease. Recently developed technologies have shown promising results in preclinical studies, but they still do not overcome the issues that native vessels present, and only a few have made the transition into clinical use. The endothelial lining is a key aspect for the success or failure of the grafts, especially on smaller diameter grafts (<5 mm). However, during the design and evaluation of the grafts, the mechanisms for the formation of this layer are not commonly examined. Therefore, a significant amount of established research might not be relevant to the clinical context, due to important differences that exist between the vascular regeneration mechanisms found in animal models and humans. This article reviews current knowledge about endothelialization mechanisms that have been so far identified: in vitro seeding, transanastomotic growth, transmural infiltration, and fallout endothelialization. Emphasis is placed on the models used for study of theses mechanisms and their effects on the development of tissue-engineering vascular conduits.

Fibronectin Adsorption on Electrospun Synthetic Vascular Grafts Attracts Endothelial Progenitor Cells and Promotes Endothelialization in Dynamic In Vitro Culture

“…The use of autografts, like the saphenous vein or mammary artery, are still the standard clinical approach for the replacement of small diameter blood vessels [3]. However, mechanical or size mismatches, and mainly the scarce availability make alternative grafts necessary [4,5]. In this context, two strategies have emerged in recent years: synthetic substitutes and biological grafts [4].…”

“…However, mechanical or size mismatches, and mainly the scarce availability make alternative grafts necessary [4,5]. In this context, two strategies have emerged in recent years: synthetic substitutes and biological grafts [4]. Although large-diameter synthetic substitutes (>6 mm) are successfully used, small diameter grafts (<6 mm) show low patency rates due to their tendency to elicit thrombosis and the formation of intimal hyperplasia [6][7][8].…”

“…Tissue engineering can be used as an alternative strategy to obtain a functional endothelium in a synthetic graft utilizing a patient's own cells [52]. After implantation, the tissue-engineered vascular graft (TEVG) is replaced by the host's cells and ECM and is thereby degraded [4]. However, the loss of mechanical properties due to a too rapid degradation and unfavorable biological reactions to the degradation products remain a major challenge [1,53].…”

Sequential adaptation of perfusion and transport conditions significantly improves vascular construct recellularization and biomechanics

“…Easing the vascular wall repopulation and biomechanical adaptation was needed for further development of ex vivo scaffolds as vascular grafts. Additional development of an endothelial layer to avoid thrombosis of the vessel upon implantation is also crucial (Sánchez, Brey, & Briceño, 2018). It has previously been demonstrated that the re-endothelialization of the acellular human umbilical vein can similarly be performed using sequential conditioning steps (Uzarski, Cores, & McFetridge, 2015).…”

Insight on the endothelialization of small silk-based tissue-engineered vascular grafts

“…45 In vivo, there are three known spontaneous modes of endothelialization: transanastomotic ingrowth, transmural capillarization, and fallout endothelialization. 46 For an extensive review on the different endothelialization mechanisms in vascular grafts, see Sánchez et al 46 Transanastomotic endothelialization consists in the growth of the host intimal layer from the anastomosis site towards the middle of the graft: native ECs migrate through the anastomosis region. 47 However, if this mechanism of endothelialization is well known and allows to fully endothelialize the short-to middle-sized grafts in animal models, it does not take place that well in human beings.…”