Rapid Engineered Small Diameter Vascular Grafts from Smooth Muscle Cells

Abstract

Smooth muscle cells (SMCs) have been extensively used as components in tissue engineered vascular grafts (TEVGs) due to their important roles in vasoactivity and blood vessel remodeling. For TEVG approaches that rely on SMC seeding of a scaffold prior to implantation, few if any utilize a highly-efficient bulk-seeding process to achieve densely and uniformly distributed cells. The objective of this study was to assess a TEVG based on a biodegradable tubular scaffold bulk-seeded with SMCs and cultured acutely in vitro. Rat SMCs were seeded into bi-layered poly(ester-urethane)urea (PEUU) scaffolds using a customized rotational vacuum seeding device. The seeded constructs were dynamically cultured in spinner flasks for 2 days and then implanted into Lewis rats as aortic interposition grafts for 8 weeks. Results showed rSMCs populated the porous layer of the constructs evenly and densely immediately after seeding. The seeding and dynamic culture processes did not affect the metabolic activity and phenotype of the rSMCs. After implantation, rSMC-seeded TEVGs showed a higher patency rate than the unseeded control (75% vs. 37.5% respectively). Patent rSMC-seeded TEVGs revealed extensive tissue remodeling consisting of multiple layers of α-smooth muscle actin- and calponin-positive cells, and a von Willebrand factor-positive monolayer lining the lumen. These results demonstrate the feasibility of quick fabrication of a SMC-based TEVG in vitro and suggest that the cells play a role in maintaining patency of the TEVG as an arterial conduit.