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

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.

Electrospun vein grafts with high cell infiltration for vascular tissue engineering.

Demand is increasing for functional small-diameter vascular grafts (diameter<6mm) for clinical arterial replacement. In the present study, we develop a bilayer poly(ε-caprolactone, PCL) fibrous vascular graft consisting of a thin internal layer made of longitudinally aligned fibers and a relatively thick highly porous external layer. The internal layer provides a scaffold with the necessary mechanical strength and enhances the growth of endothelial cells, whereas the external layer enhances cell motility through the scaffold bulk. The biocompatibility and biological performance of bilayer fibrous scaffolds are evaluated by in vivo experiments, molecular biology, and histology studies. Our bilayer scaffolds demonstrate much better fiber alignment and higher porosity than do normal electrospun vascular grafts with randomly distributed fibers. The results suggest that the proposed grafts can overcome limitations owing to the inadequate porosity, small pores, and poor cell infiltration of scaffolds fabricated by conventional electrospinning. The unique structure of bilayer scaffolds is satisfactory and promotes cell proliferation, collagen-fiber deposition, and ingrowth of smooth muscle cells and endothelial cells in vivo. The results of this study illustrate the strong potential of such bilayer fibrous scaffolds for vascular tissue engineering and regeneration.

Composite vascular grafts with high cell infiltration by co-electrospinning.

There is an increasing demand for functional small-diameter vascular grafts (diameter<6mm) to be used in clinical arterial replacement. An ideal vascular graft should have appropriate biomechanical properties and be biocompatible. Electrospinning has become a popular polymer processing technique for vascular tissue engineering, but the grafts fabricated by electrospinning often have relatively small pores and low porosity, which limit cell infiltration into scaffolds and hinder the regeneration and remodeling of grafts. In the present study, we aimed to develop an efficient method to prepare electrospun composite vascular grafts comprising natural and synthetic materials. We fabricated grafts made of polycaprolactone, gelatin, and polyvinyl alcohol (PVA) by co-electrospinning, and the scaffolds were further functionalized by immobilizing heparin on them. The PVA fibers degraded rapidly in vivo and generated electrospun scaffolds with high porosity, which significantly enhanced cell proliferation and infiltration. The mechanical properties of the grafts are suitable for use in artery replacement. Heparin functionalization of the grafts yielded a good antithrombogenic effect, which was demonstrated in platelet adhesion tests. Moreover, in vitro and in vivo results demonstrated that the heparin release from the grafts enhanced the growth of endothelial cells, which is important for the endothelium of implanted grafts. The results of this study indicate that our method is effective and controllable for the fabrication of vascular grafts that meet the clinical requirements for blood vessel transplantation.