title: Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model.
abstract: To address the growing demand of small-diameter vascular grafts for cardiovascular disease, it is necessary to develop substitutes with bio-functionalities, such as anticoagulation, rapid endothelialization, and smooth muscle regeneration. In this study, the small-diameter tubular grafts (2.2 mm) were fabricated by electrospinning of biodegradable polymer polycaprolactone (PCL) followed by functional surface coating with an arginine-glycine-aspartic acid (RGD)-containing molecule. The healing characteristics of the grafts were evaluated by implanting them in rabbit carotid arteries for 2 and 4 weeks. Results showed that at both time points, all 10 of the RGD-modified PCL grafts (PCL-RGD) were patent, whereas 4 of the 10 non-modified PCL grafts were occluded due to thrombus formation. Scanning electron microscopy (SEM) data showed abundant platelets adhering on the surface of the midportion of the PCL grafts. In contrast, only few platelets were observed on the PCL-RGD surface, suggesting that RGD modification significantly improved the hemocompatibility of the PCL grafts. Histological analysis demonstrated enhanced cell infiltration and homogeneous distribution within the PCL-RGD grafts in comparison with the PCL grafts. Furthermore, immunofluorescence staining also showed a 3-fold increase of endothelial coverage of the PCL-RGD grafts than that of PCL grafts at those two time points. After 4-week implantation, 65.3 ± 7.6% of the surface area of the PCL-RGD grafts was covered by smooth muscle cell layer, which is almost 23% more than that on the PCL grafts. The present study indicates that RGD-modified PCL grafts exhibit an improved remodeling and integration capability in revascularization.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Zheng
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.forename: Lijie
authors.initials: L
authors.lastname: Song
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Shufang
authors.initials: S
authors.lastname: Wang
authors.forename: Jihong
authors.initials: J
authors.lastname: Han
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Yang
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D011091:Polyesters / Q000494:pharmacology; D019919:Prosthesis Implantation; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects; D058017:Vascular Grafting; D014654:Vascular Patency / Q000187:drug effects*
chemical_list: D009842:Oligopeptides; D011091:Polyesters; C016240:polycaprolactone; C047981:arginyl-glycyl-aspartic acid