Accelerated neovascularization and endothelialization of vascular grafts promoted by covalently bound laminin type 1

Abstract

Development of a small diameter (<6 mm) synthetic vascular graft with clinically acceptable patency must overcome the inherent thrombogenicity of polymers and the development of neointimal thickening. Establishment of an endothelial cell lining on the lumenal surface has been hypothesized as a mechanism to improve the function of vascular grafts. The major aim of this study was to evaluate the use of laminin type 1, covalently bound to all surfaces of ePTFE grafts on neovascularization of the interstices and lumenal surface endothelialization. One mm i.d. vascular grafts were surface modified through covalent attachment of laminin type 1. Grafts were subsequently implanted as interpositional aortic grafts in rats. Following five weeks implantation the grafts were explanted and morphologically evaluated using scanning electron microscopy and light microscopy. Scanning electron microscopy identified an extensive coverage of antithrombogenic cells on the lumenal flow surface of laminin type 1 modified grafts. Histological evaluation confirmed the presence of endothelial cells on the mid-graft lumenal surface of laminin 1 modified grafts. Extensive neovascularization of the interstices of the laminin modified grafts occurred as compared to control grafts. We conclude that surface modification using laminin type 1 accelerates both the neovascularization and endothelialization of porous ePTFE vascular grafts.

In vitro and ex vivo hemocompatibility of off-the-shelf modified poly(vinyl alcohol) vascular grafts

“…For example, mimicking the fibrillar ECM structure in the form of micron-sized gratings on synthetic surfaces has been shown to increase migration and retention under shear stress [15], improve proliferation [16] and retain the atheroprotective phenotype [17] of endothelial cells. Additionally, functionalization of synthetic surfaces with ECM proteins, such as fibronectin [18], vitronectin [19] and laminin [20] were shown to improve endothelial cell attachment. Anucleate platelets are also sensitive to both biochemical and biophysical cues [21,22], showing changes in morphology and activation.…”

Strategies and Techniques to Enhance theIn SituEndothelialization of Small-Diameter Biodegradable Polymeric Vascular Grafts

“…[69][70][71][72] Laminin type 1 has been utilized in ePTFE grafts, demonstrating enhanced endothelialization over unmodified grafts. 73 While laminin-derived RGD continues to be one of the more popular ECM-derived peptides to enhance endothelialization, 74 a variety of other peptide sequences derived from fibronectin, laminin, and collagen type I have been incorporated into vascular grafts.…”

Vascular Grafting Strategies in Coronary Intervention

“…The presence of red cells, leukocytes, fibrin, and platelets in the control grafts suggested a highly thrombogenic surface, while the laminin type 1 conjugated grafts exhibited a complete lining of cells, indicative of an intact endothelium as shown in Figure 2. The authors also observed neovascularization in the interstices of the ePTFE grafts in the laminin-conjugated grafts (Williams et al, 2011).…”