Optimizing Small-Diameter Vascular Grafts: Harnessing the Power of Recombinant Human Type III Collagen (rhcoliii) for Enhanced Antiplatelet and Endothelialization Performance
Chemical Engineering Journal(2024)
摘要
Small-diameter vascular grafts hold great promise as potential substitutes for coronary and peripheral arteries. However, their clinical availability is hindered by thrombogenicity and intimal hyperplasia. Herein, bilayer vascular grafts with enhanced antithrombogenicity and endothelialization were developed by two-step electrospinning technology. First, the well-designed recombinant human type III collagen (rhCOLIII), featuring numerous triplets that promote cell adhesion while excluding sequences prone to platelet adhesion and activation, was composited with poly(L-lactide-co-ε-caprolactone) (PLCL) to create a bioactive inner layer. Afterward, a pure PLCL outer layer with exceptional elasticity was constructed to provide mechanical support. In vitro antiplatelet and cytocompatibility experiments revealed that the graft containing 60% rhCOLIII exhibited almost no platelet adhesion, while the number of adhered endothelial cells increased approximately 20 times compared to pure PLCL. Furthermore, Beagle dog femoral artery implantation models demonstrated that the rhCOLIII-modified grafts underwent endothelialization within three months, contributing to the patency of grafts. The potential mechanism for enhanced endothelialization by rhCOLIII was investigated through transcriptome sequencing and verified by an integrated analysis of gene and protein expression. The cell-affinity units, Gly-Glu-Arg (GER) and Gly-Glu-Lys (GEK) triplets, present in rhCOLIII contribute to initial adhesion of endothelial cells. Following adhesion, they may upregulate the expression of integrins αVβ8 on the cell surface, thereby further enhancing cell adhesion. Subsequently, the FAK/PI3K/AKT pathway within endothelial cells may also be activated to promote cell proliferation.
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关键词
Vascular grafts,Recombinant human type III collagen,Endothelialization,Antiplatelet,Electrospinning
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