Journal
ADVANCED FIBER MATERIALS
Volume 4, Issue 6, Pages 1685-1702Publisher
SPRINGERNATURE
DOI: 10.1007/s42765-022-00213-z
Keywords
VE-cadherin/VEGF; Bioactive surface; Biomimetic endothelium microenvironment; Electrospun PCL vascular grafts; Rapid endothelialization
Funding
- National Key RAMP
- D Program of China [2020YFA0710802]
- National Natural Science Foundation of China [32071364, 82172106]
- NCC Fund [NCC2020PY18]
- Tianjin Project + Team Key Training Foundation [XC202035]
- China Postdoctoral Science Foundation [2022M711707]
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In this study, a novel bioactive surface integrating human VE-cadherin-Fc and VEGF-Fc fusion proteins was developed for the modification of electrospun fibrous grafts, which promoted the regeneration of functional endothelium and improved the patency of artificial vascular grafts. The VE-cadherin/VEGF surface upregulated the expression of endogenous VE-cadherin and activated the signaling pathways related to endothelial function. Additionally, it enhanced cellularization and capillary formation, leading to accelerated regeneration of functional endothelium and smooth muscle.
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(epsilon-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.
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