title: Improved hemocompatibility and endothelialization of vascular grafts by covalent immobilization of sulfated silk fibroin on poly(lactic-co-glycolic acid) scaffolds.
abstract: Endothelialization of vascular grafts prior to implantation has been investigated widely to enhance biocompatibility and antithrombogenicity. Thrombosis of artificial vessels is typically caused by platelet adhesion and agglomeration following endothelial cells detachment when exposed to the shear stress of blood circulation. The present study thus aimed at preventing platelet adhesion and aggregation onto biomaterials before the endothelial confluence is fully achieved. We report this modification of poly(lactic-co-glycolic acid) (PLGA) scaffolds, both to impart hemocompatibility to prevent platelet adhesion and aggregation before the endothelial confluence is fully achieved and to support EC growth to accelerate endothelialization. The modification was achieved by covalent immobilization of sulfated silk fibroin on PLGA scaffolds using γ irradiation. Using phosphate-buffered saline (PBS) as an aging medium, it was demonstrated that the scaffolds prepared by γ irradiation had a good retention of sulfated silk fibroin. The systematic in vitro hemocompatibility evaluation revealed that sulfated silk fibroin covalently immobilized PLGA (S-PLGA) scaffolds-reduced platelet adhesion and activation, prolonged whole blood clotting time, activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). To evaluate further in vitro cytocompatibility of the scaffolds, we seeded vascular ECs on the scaffolds and cultured them for 2 weeks. The ECs were seen to attach and proliferate well on S-PLGA scaffolds, forming cell aggregates that gradually increased in size and fused with adjacent cell aggregates to form a monolayer covering the scaffold surface. Moreover, it was demonstrated through the gene transcript levels and the protein expressions of EC-specific markers that the cell functions of ECs on S-PLGA scaffolds were better preserved than those on PLGA scaffolds. Therefore, this study has described the generation of a vascular graft that possesses the unique ability to display excellent hemocompatibility while simultaneously supporting extensive endothelialization.
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, People's Republic of China. haifengliu@buaa.edu.cn
authors.forename: Haifeng
authors.initials: H
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.forename: Xufeng
authors.initials: X
authors.lastname: Niu
authors.forename: Gang
authors.initials: G
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
mesh_terms: D001672:Biocompatible Materials; D001769:Blood; D001807:Blood Vessel Prosthesis; D002448:Cell Adhesion; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005349:Fibroins; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D010974:Platelet Aggregation; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D060888:Real-Time Polymerase Chain Reaction; D047011:Silk; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001672:Biocompatible Materials; D047011:Silk; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA; D005349:Fibroins