Syndecan‐4 and stromal cell‐derived factor‐1 alpha functionalized endovascular scaffold facilitates adhesion, spreading and differentiation of endothelial colony forming cells and functions under flow and shear stress conditions

Abstract

Acellular vascular scaffolds with capture molecules have shown great promise in recruiting circulating endothelial colony forming cells (ECFCs) to promote in vivo endothelialization. A microenvironment conducive to cell spreading and differentiation following initial cell capture are key to the eventual formation of a functional endothelium. In this study, syndecan-4 and stromal cell-derived factor-1 alpha were used to functionalize an elastomeric biomaterial composed of poly(glycerol sebacate), Silk Fibroin and Type I Collagen, termed PFC, to enhance ECFC-material interaction. Functionalized PFC (fPFC) showed significantly greater ECFCs capture capability under physiological flow. Individual cell spreading area on fPFC (1474 ± 63 μm 2 ) was significantly greater than on PFC (1187 ± 54 μm 2 ) as early as 2 h, indicating enhanced cell-material interaction. More-

Syndecan-4 Functionalization Reduces the Thrombogenicity of Engineered Vascular Biomaterials

“…Previous studies in our laboratory have shown PFC to be an elastomeric composite material with compositional, structural, and mechanical similarities to coronary arteries [18]. PFC fabricated as small-diameter grafts had viscoelastic properties and performed mechanically under physiological flow and pressure [34]. In preliminary studies, it was demonstrated that platelets adhered to PFC fibers but were not activated compared to collagen fibers [18].…”

“…In a previous study, we demonstrated syndecan-4 significantly enhanced the binding of growth factors to PFC and resulted in an increased capture of endothelial colony-forming cells (ECFCs) [33]. In a further study, we demonstrated syndecan-4 functionalization of PFC promoted spreading and differentiation of ECFCs [34].…”

“…While not a part of the current study, it is possible that syndecan-4 functionalization might improve the long-term performance of biomaterial implants in general through the interaction of heparan sulfate with the molecules critical in maintaining hemostasis. For example, we previously reported that PFC_SYN4 facilitated the binding of stromal cell-derived factor-1alpha and promoted the specific binding and differentiation of endothelial colony-forming cells, all processes that are critical in the formation of a non-thrombogenic endothelium [33,34].…”