Highly aligned core-shell structured nanofibers for promoting phenotypic expression of vSMCs for vascular regeneration

This study was designed to assess the efficacy of hyaluronan (HA) functionalized well-aligned nanofibers of poly-l-lactic acid (PLLA) in modulating the phenotypic expression of vascular smooth muscle cells (vSMCs) for blood vessel regeneration. Highly aligned HA/PLLA nanofibers in core-shell structure were prepared using a novel stable jet electrospinning approach. Formation of a thin HA-coating layer atop each PLLA nanofiber surface endowed the uni-directionally oriented fibrous mats with increased anisotropic wettability and mechanical compliance. The HA/PLLA nanofibers significantly promoted vSMC to elongation, orientation, and proliferation, and also up-regulated the expression of contractile genes/proteins (e.g., α-SMA, SM-MHC) as well as the synthesis of elastin. Six weeks of in vivo scaffold replacement of rabbit carotid arteries showed that vascular conduits made of circumferentially aligned HA/PLLA nanofibers could maintain patency and promoted oriented vSMC regeneration, lumen endothelialization, and capillary formation. This study demonstrated the synergistic effects of nanotopographical and biochemical cues in one biomimetic scaffold design for efficacious vascular regeneration.