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

Abstract

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(3-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-a-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.

Direct E-jet printing of three-dimensional fibrous scaffold for tendon tissue engineering

“…The elicitation of cellular elongation during direct mechanotransduction could cause aligned cytoskeletonal fibers to trigger nucleus deformation. Such nucleus deformation would further lead to the structural adjustment of the DNA and nucleus pores, and the accessibility of transcriptional factors would be changed, resulting in alteration of gene expression . Our observations indicated that the orientated E‐jetted fibers had contributions to cell elongation, and gene expression toward tendon tissue through such mechanotransduction pathways, which suggested that the as‐fabricated scaffold has potential for tendon regeneration.…”

Degradation behaviors of geometric cues and mechanical properties in a 3D scaffold for tendon repair

“…Results in this study also demonstrated that the tenocytes elongated in a direction which was parallel to the geometric cures. The cellular alignment and elongation induced from the geometric cures further enhanced the expression levels of tendious genes via the mechanotransduction pathway …”

An in vivo study of a gold nanocomposite biomaterial for vascular repair

“…These approaches have involved biomaterials that utilize both chemical [40–42] and topographical modifications [43, 44] to regulate smooth muscle cells (SMCs) over-proliferation and enhance ECM synthesis as well as other innovative biomaterials that are impregnated with stem cells and/or utilize biomechanical stimulation to improve overall biocompatibility [41, 45]. …”

“…Growth factors such as transforming growth factor (TGF-β1) have also been conjugated to fibrin hydrogel vascular grafts and exposed to mechanical stimulation [41] to improve mechanical properties and ECM content. Mechanical stimulation has also been combined with mesenchymal stem cells (MSCs) cultured on micropatterned poly(e-caprolactone) films for improved functionally of SMCs [45]. Another study electrospun a larger pore and thicker polycaprolactone (PCL) fiber to construct vascular grafts that demonstrated immunomodulatory properties resulting in vascular regeneration [43].…”