Aligned core-sheath structured fibers prevent intimal hyperplasia via modulate macrophage polarization and smooth muscle cell phenotype in vascular regeneration.

Small-diameter vascular grafts face limited success due to thrombosis, intimal hyperplasia, and insufficient remodeling. Here, we developed a tubular graft composed of aligned core-sheath structured PLCL fibers with sodium tanshinone IIA sulfonate (STS)-loaded polyethylene oxide (PEO) cores. The graft exhibited uniform structures, appropriate porosity, and matched mechanical properties. In vitro, aligned fibers enhanced smooth muscle cell (VSMC) proliferation and promoted a contractile phenotype (α-SMA, SM-MHC). Simultaneously, STS delivery modulated macrophage polarization, suppressing iNOS (M1-like) and enhancing CD206 (M2-like) expression. Co-culture assays revealed reciprocal regulation between VSMCs and macrophages, where VSMCs aligned and matured under macrophage-mediated anti-inflammatory cues, while contractile VSMCs reinforced M2-like polarization. These interactions effectively reduced intimal hyperplasia by preventing excessive smooth muscle cell proliferation and promoting a stable, anti-inflammatory microenvironment. In vivo rat implantation confirmed patency, endothelialization, and organized extracellular matrix resembling native vessels. These findings highlight the combined effect of graft design, macrophage and smooth muscle cell modulation, and cell-cell crosstalk in preventing intimal hyperplasia and driving vascular regeneration, offering a versatile strategy for functional small-diameter vascular grafts.