The effect of thick fibers and large pores of electrospun poly(ε-caprolactone) vascular grafts on macrophage polarization and arterial regeneration

The vascular grafts prepared by electrospinning often have relatively small pores, which limit cell infiltration into the grafts and hinder the regeneration and remodeling of the grafts into neoarteries. To overcome this problem, macroporous electrospun polycaprolactone (PCL) scaffolds with thicker fibers (5-6 μm) and larger pores (∼30 μm) were fabricated in the present study. In vitro cell culture indicated that macrophages cultured on thicker-fiber scaffolds tended to polarize into the immunomodulatory and tissue remodeling (M2) phenotype, while those cultured on thinner-fiber scaffolds expressed proinflammatory (M1) phenotype. In vivo implantation by replacing rat abdominal aorta was performed and followed up for 7, 14, 28 and 100 d. The results demonstrated that the macroporous grafts markedly enhanced cell infiltration and extracellular matrix (ECM) secretion. All grafts showed satisfactory patency for up to 100 days. At day 100, the endothelium coverage was complete, and the regenerated smooth muscle layer was correctly organized with abundant ECM similar to those in the native arteries. More importantly, the regenerated arteries demonstrated contractile response to adrenaline and acetylcholine-induced relaxation. Analysis of the cellularization process revealed that the thicker-fiber scaffolds induced a large number of M2 macrophages to infiltrate into the graft wall. These macrophages further promoted cellular infiltration and vascularization. In conclusion, the present study confirmed that the scaffold structure can regulate macrophage phenotype. Our thicker-fiber electrospun PCL vascular grafts could enhance the vascular regeneration and remodeling process by mediating macrophage polarization into M2 phenotype, suggesting that our constructs may be a promising cell-free vascular graft candidate and are worthy for further in vivo evaluation.