A metal-organic-framework incorporated vascular graft for sustained nitric oxide generation and long-term vascular patency

Abstract

Copper-MOFs (Cu-MOFs) have been reported to demonstrate great potential as cardiovascular biomaterials, due to enhanced catalytic ability of Cu2+ to generate nitric oxide (NO) from endogenous S-nitrosothiols (RSNOs). However, free Cu-MOFs usually show rapid degradation under physiological conditions, resulting in short catalytic half-life and risk of copper ion toxicity. Therefore, how to increase the stability of Cu-MOFs is of great importance in cardiovascular biomaterials research. Herein, we chose M199 MOF as an example and developed Cu-MOF-based scaffold, using the electrospinning method to embed Cu-MOF nanoparticles into polycaprolactone (PCL) fibers. Entrapment of Cu-MOF nanoparticles within PCL could simultaneously enhance Cu-MOF stability in serum and allow for long-term NO catalytic activity, as assessed by in vitro assays and using in situ implantation models. Additionally, the optimized concentration of Cu-MOFs loaded within the scaffolds significantly promoted endothelial cell (EC) migration and increased acetylated low-density lipoprotein (Ac-LDL) uptake. Moreover, Cu-MOF-based scaffolds dramatically inhibited platelet adhesion and activation, which markedly reduced acute thrombosis in arterio-venous shunt models. In situ implantation experiments revealed that the PCL/Cu-MOF scaffolds accelerated the formation of an intact endothelial monolayer. Together, these results suggest that the incorporation of Cu-MOFs into electrospun fibers could serve as a promising approach to achieve stable catalytic performance and long-term activity required for implant materials.