title: 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.
authors.affiliation: Department of Vascular Surgery, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Hankou Road, Nanjing, China. zhouminnju@gmail.com
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Wei
authors.forename: Changjian
authors.initials: C
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Qiao
authors.forename: Feng
authors.initials: F
authors.lastname: Ran
authors.forename: Yan
authors.initials: Y
authors.lastname: Bai
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D042783:Endothelial Cells; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000378:metabolism; D014654:Vascular Patency
chemical_list: D020099:Coated Materials, Biocompatible; D042461:Vascular Endothelial Growth Factor A; D006493:Heparin