Three-dimensional silk fibroin microsphere-nanofiber scaffolds for vascular tissue engineering

Abstract

A significant limitation in the engineering of artificial small-diameter vascular scaffolds is that the number of endothelial cells (ECs) is not sufficient to generate a confluent coverage of the vascular scaffolds, so that the surfaces of vascular scaffolds form thrombus via platelet adhesion and aggregation. Thrombus decrease relies on three-dimensional (3D) scaffolds to mimic the natural extracellular matrix (ECM) as templates to regulate cell behavior and facilitate tissue maturation. Here, we developed 3D scaffolds consisting of silk fibroin (SF) nanofibers and homogeneous microspheres by electrospinning and microfluidics. The nanofibers with diameters ranging from 250 to 350 ​nm doped with microspheres (2–10 ​μm) formed bridge-shaped structures. ECs were seeded and maintained on the 3D microsphere-nanofiber scaffolds with a mean fiber diameter of 300 ​nm. A 10% higher ratio of cell proliferation on 3D microsphere-nanofiber SF scaffolds was noted as compared to that on microporous and sponge-like SF scaffolds with small surface network fabricated by freeze-drying. Moreover, the gene transcript levels including CD146, VE-C and PECAM-1 were better preserved on 3D microsphere-nanofiber SF scaffolds than those on freeze-dried scaffolds. Thus, the developed 3D microsphere-nanofiber structure may have a myriad of applications in vascular tissue engineering scaffolds and cardiovascular devices.