Triple-Layer Vascular Grafts Fabricated by Combined E-Jet 3D Printing and Electrospinning

Abstract

Small-diameter tissue-engineered vascular grafts are urgently needed for clinic arterial substitute. To simulate the structures and functions of natural blood vessels, we designed a novel triple-layer poly(ε-caprolactone) (PCL) fibrous vascular graft by combining E-jet 3D printing and electrospinning techniques. The resultant vascular graft consisted of an interior layer comprising 3D-printed highly aligned strong fibers, a middle layer made by electrospun densely fibers, and an exterior structure composed of mixed fibers fabricated by co-electrospraying. The biocompatible triple-layer graft was used for in vivo implantation, and results demonstrated that the longitudinally-aligned fibers within the lumen of the graft could enhance the proliferation and migration of endothelial cells, while maintained good mechanical properties. The exterior layer provided a pathway that encouraged cells to migrate into the scaffold after implantation. This experimental graft overcame the limitations of conventionally electrospun vascular grafts of inadequate porosity and lowly cell penetration. The unique structure of the triple-layer vascular graft promoted cell growth and infiltration in vivo, thus provided an encouraging substitute for in situ tissue engineering.

Strategies in cell‐free tissue‐engineered vascular grafts

“…The longitudinally aligned fibers significantly promoted ECs proliferation and migration, and good cell infiltration was observed in the exterior layer (Huang et al, 2018). At first, the effect of porosity and pore size was demonstrated to be a critical factor which was associated with cell infiltration.…”

“…Researchers have made great strides in the development of constructs at the nanoscale that interact with cells and cause blood vessel formation. Previous studies found that the ECM compositions and topography have an influence on the function of ECs (Kumbar, James, Nukavarapu, & Laurencin, 2008;Peran et al, 2012;Viswanathan et al, 2015;Wilgus, 2012 longitudinally-aligned strong PCL fibers, which afforded the graft the essential mechanical support and promoted the growing, spreading, and migration of ECs (Huang et al, 2018).…”

“…Previous studies found that the ECM compositions and topography have an influence on the function of ECs (Kumbar, James, Nukavarapu, & Laurencin, 2008;Peran et al, 2012;Viswanathan et al, 2015;Wilgus, 2012 longitudinally-aligned strong PCL fibers, which afforded the graft the essential mechanical support and promoted the growing, spreading, and migration of ECs (Huang et al, 2018). Previous studies found that the ECM compositions and topography have an influence on the function of ECs (Kumbar, James, Nukavarapu, & Laurencin, 2008;Peran et al, 2012;Viswanathan et al, 2015;Wilgus, 2012 longitudinally-aligned strong PCL fibers, which afforded the graft the essential mechanical support and promoted the growing, spreading, and migration of ECs (Huang et al, 2018).…”

“…Thus the number of ECs and EPCs in the circulation, the proliferation and differentiation properties of these cells, and the capability of the lumen surface to recruit and adhere these cells become critical for endothelialization. The longitudinally-aligned fibers within the lumen of the graft could enhance the proliferation and migration of ECs (Huang et al, 2018). Therefore, the construction of a functional blood-contacting surface has significant importance to TEVG investigation.…”

“…These natural topographical features may provide an increased cellular attachment as well as alignment in the direction of blood flow (Radke et al, 2018). The longitudinally-aligned fibers within the lumen of the graft could enhance the proliferation and migration of ECs (Huang et al, 2018 (Speer et al, 2009;Sun et al, 2012). On the other hand, the uncontrolled constriction of SMCs will result in myocardial ischemia after implantation.…”