Effect of Resveratrol on Modulation of Endothelial Cells and Macrophages for Rapid Vascular Regeneration from Electrospun Poly(ε-caprolactone) Scaffolds

Rapid endothelialization is a key factor that determines the success of small-diameter vascular grafts as an artery substitute in the treatment of cardiovascular diseases. Aimed to facilitate vascular regeneration, we developed a vascular scaffold loaded with resveratrol, which is a natural compound extracted from plants and showed multifaceted effects in cardiovascular protection. The tubular poly(epsilon-caprolactone) (PCL) scaffold was prepared by electrospinning with resveratrol in the PCL solution. In vitro assay demonstrated that resveratrol could be released from the scaffolds in a sustained and controlled manner. Cell culture results indicated that the migration of endothelial cells (ECs), nitric oxide production, and the ability of tube formation increased in the resveratrol-containing PCL scaffold groups compared with the PCL control. Meanwhile, the level of tumor necrosis factor (TNF)-alpha, the main proinflammatory factor secreted from macrophages, was reduced, and the messenger RNA expressions of the M2 macrophage-related genes were increased in the resveratrol-containing group. Further, in vivo implantation was performed by replacing rat abdominal aorta. We observed fast endothelialization and enhanced vascular regeneration in rats with resveratrol-containing scaffolds. The presence of resveratrol also induced a large number of M2 macrophages to infiltrate into the graft wall. Taken together, the incorporation of resveratrol into the PCL grafts enhanced the vascular regeneration by modulation of ECs and macrophages.