摘要
In vivo,vascular endothelial growth factor(VEGF)and vascular endothelial cadherin(VE-cadherin)co-regulate the dynamic organization of endothelial cells during vascular sprouting,balancing angiogenesis and vascular stability.In this study,a novel bioactive surface integrating human VE-cadherin-Fc and VEGF-Fc fusion proteins was innovatively developed for the modification of poly(ε-caprolactone)(PCL)small-caliber electrospun fibrous grafts(VE-cad/VEGF-PCL)to promote the regeneration of functional endothelium and improve the patency of artificial vascular grafts.These fusion proteins self-assembled on the PCL fibers through the hydrophobic binding of Fc domains,improving surface hydrophilicity while reducing the adhesion of fibrinogen.In vitro results showed that the VE-cadherin/VEGF surface upregulated the expression of endogenous VE-cadherin and synergistically activated the VE-cadherin/VEGFR2/FAK/AKT/ERK signal transduction,which facilitated the functioning of human umbilical vein endothelial cells(HUVECs).Moreover,the VE-cadherin/VEGF surface significantly enhanced cellularization and capillary formation,then subsequently accelerated the regeneration of functional endothelium and smooth muscle in the VE-cad/VEGF-PCL grafts in a rat abdominal aorta replacement model.Together,these results highlight the advantages of VE-cadherin/VEGF surface in enhancing rapid endothelialization of electrospun vascular grafts and provide new insights into the design of cross-activating biomaterials.
基金
The authors gratefully acknowledge financial support from the National Key R&D Program of China(2020YFA0710802)
the National Natural Science Foundation of China(Grant No.32071364,82172106)
the NCC Fund(NCC2020PY18)
Tianjin“Project+Team”Key Training Foundation(XC202035)
China Postdoctoral Science Foundation(2022M711707).
