Development and characterization of a porous micro-patterned scaffold for vascular tissue engineering applications

Abstract

The fabrication of functional small diameter blood vessel analogs has implications in vascular disease treatment. Current 3D models of the medial vessel layer lack micron-scale topographical cues that have shown promise in vitro by recapitulating native vascular smooth muscle cell (VSMC) behavior. A major obstacle to fabricating 3D scaffolds is maintaining adequate nutrient diffusion to cells. We have developed and characterized porous micro-patterned poly-caprolactone (PCL) scaffolds using a novel technique that integrates soft lithography, melt molding and particulate leaching of polylactic-co-glycolic acid (PLGA) micro/nanoparticles. Scanning electron microscopy showed that PLGA-leached scaffolds have circular pores significantly smaller than the size scale of the grooved surface pattern (48 microm grooves; 5 microm deep; 12 microm spacing). Diffusion of media through PLGA-leached scaffolds was six-fold greater than through non-porous scaffolds, indicating successful introduction of through-pores into PCL by the PLGA leaching technique. VSMC alignment on micro-patterned PLGA-leached scaffolds was similar to that on micro-patterned non-porous scaffolds, indicating no loss in cellular organization on PLGA-leached scaffolds. In contrast, cells seeded on micro-patterned sodium bicarbonate-leached scaffolds remained un-aligned. The ability to micro-pattern cells on porous scaffolds may facilitate the transfer of micro-technology from simple 2D substrates to complex 3D architectures, allowing for tight control over cellular organization in fabricated tissues.