Enhancing mesenchymal stem cell response using uniaxially stretched poly(ε-caprolactone) film micropatterns for vascular tissue engineering application

Regeneration of tunica media with anisotropic architecture still remains a challenging issue for vascular tissue engineering (TE). Herein, we present the development of flexible poly(epsilon-caprolactone) (PCL) film micropatterns to regulate mesenchymal stem cells (MSCs) function for tunica media construction. Results showed that uniaxial thermal stretching of PCL films resulted in topographical micropatterns comprising of ridges/grooves, and improved mechanical properties, including yield stress, Young's modulus, and fracture stress without sacrificing film elasticity. Culturing on such PCL film micropatterns, MSCs self-aligned along the ridges with a more elongated morphology as compared to that of the unstretched film group. Moreover, MSCs obtained a contractile SMCs-like phenotype, with ordered organization of cellular stress filaments and upregulated expression of the contractile makers, including SM-alpha-actin calponin, and SM-MHC. The PCL film micropatterns could be rolled into a small-diameter 3D tubular scaffold with circumferential anisotropy of ridges/grooves, and in the incorporation of MSCs, which facilitated a hybrid sandwich-like vascular wall construction with ordered cell architecture similar to that of the tunica media. These results provide insights of how geometric cues are able to regulate stem cells with desired functions and have significant implications for the designing of a functionalized vascular TE scaffold with appropriate topographical geometries for guiding tunica media regeneration with microscale control of cell alignment and genetic expression.