Development and Validation of Small‐diameter Vascular Tissue From a Decellularized Scaffold Coated With Heparin and Vascular Endothelial Growth Factor

Abstract

To overcome shortcomings of current small-diameter vascular prostheses, we developed a novel allogenic vascular graft from a decellularized scaffold modified through heparin immobilization and vascular endothelial growth factor (VEGF) coating. The VEGF coating and release profiles were assayed by enzyme-linked immunosorbent assay, the biological activity of modified surface was validated by human umbilical vein endothelial cells seeding and proliferation for 10 days in vitro. In vivo, we implanted either a modified or a nonmodified scaffold as bilateral carotid allogenic graft in canines (n = 15). The morphological examination of decellularized scaffolds showed complete removal of cellular components while the extracellular matrix structure remained intact. After modification, the scaffolds possessed local sustained release of VEGF up to 20 days, on which the cells cultured showed significantly higher proliferation rate throughout the time after incubation compared with the cells cultured on nonmodified scaffolds (P < 0.0001). After 6 months of implantation, the luminal surfaces of modified scaffolds exhibited complete endothelium regeneration, however, only a few disorderly cells and thrombosis overlay the luminal surfaces of nonmodified scaffolds. Specifically, the modified scaffolds exhibited significantly smaller hyperplastic neointima area compared with the nonmodified, not only at midportion (0.56 +/- 0.07 vs. 2.04 +/- 0.12 mm(2), P < 0.0001), but also at anastomotic sites (1.76 +/- 0.12 vs. 3.67 +/- 0.20 mm(2), P < 0.0001). Moreover, modified scaffolds had a significantly higher patency rate than the nonmodified after 6 months of implantation (14/15 vs. 7/15, P = 0.005). Overall, this modified decellularized scaffold provides a promising direction for fabrication of small-diameter vascular grafts.

A polymer–extracellular matrix composite with improved thromboresistance and recellularization properties

“…For example, incorporating growth factors such as vascular endothelial growth factor (VEGF) [33], stromal cell-derived factor-1α (SDF-1α) [34] or granulocyte-colony stimulating factor (G-CSF) [35] into decellularized arterial scaffolds showed increased endothelial cell recruitment in various animal models, including canine carotid artery interposition model [33], rat carotid artery interposition model [34], and rat abdominal aorta interposition model [35]. Autologous recellularization with endothelial progenitor cells isolated from canine[36] or sheep[37] peripheral blood prior to implanting into canine/sheep carotid artery interposition models also led to decreased intimal hyperplasia and improved graft patency.…”

Cytocompatibility of electrospun nanofiber tubular scaffolds for small diameter tissue engineering blood vessels

“…Arterial replacement is now a common treatment for vascular diseases, with more than 1.4 million arterial bypass grafting performed each year in the United States [3]. Autologous or allografts are widely used to reconstruct small diameter blood vessel currently [4][5][6]. Due to inadequate sources and potential immunogenicity, however, they can't meet the requirements of small-diameter vascular graft [7].…”

Bioartificial fabrication of regenerating blood vessel substitutes: requirements and current strategies

“…Thus, besides tissue-specific cellular components, a cell-feeding infrastructure (vasa vasorum) is mandatory. Here, factors known to facilitate angiogenesis, e.g., vascular endothelial growth factor (VEGF) or cysteine-rich angiogenic protein 61 (CYR61; cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed family member 1 (CCN1)), can act supportive [5,112]. Furthermore, in the case of decellularized matrices of allogeneic or xenogeneic origin, the surface coating may also help to reduce the time between implantation of the still "immunological inductive" graft [6] and its subsequent in vivo autologization, consequently decreasing the antigenic potential of the matrix by masking respective epitopes.…”