title: Urokinase receptor counteracts vascular smooth muscle cell functional changes induced by surface topography.
abstract: Current treatments for human coronary artery disease necessitate the development of the next generations of vascular bioimplants. Recent reports provide evidence that controlling cell orientation and morphology through topographical patterning might be beneficial for bioimplants and tissue engineering scaffolds. However, a concise understanding of cellular events underlying cell-biomaterial interaction remains missing. In this study, applying methods of laser material processing, we aimed to obtain useful markers to guide in the choice of better vascular biomaterials. Our data show that topographically treated human primary vascular smooth muscle cells (VSMC) have a distinct differentiation profile. In particular, cultivation of VSMC on the microgrooved biocompatible polymer E-shell induces VSMC modulation from synthetic to contractile phenotype and directs formation and maintaining of cell-cell communication and adhesion structures. We show that the urokinase receptor (uPAR) interferes with VSMC behavior on microstructured surfaces and serves as a critical regulator of VSMC functional fate. Our findings suggest that microtopography of the E-shell polymer could be important in determining VSMC phenotype and cytoskeleton organization. They further suggest uPAR as a useful target in the development of predictive models for clinical VSMC phenotyping on functional advanced biomaterials.
authors.affiliation: Nephrology Department, Hannover Medical School, Carl-Neuberg Str. 1, Hannover 30625, Germany.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Kiyan
authors.forename: Kestutis
authors.initials: K
authors.lastname: Kurselis
authors.forename: Roman
authors.initials: R
authors.lastname: Kiyan
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Boris N
authors.initials: BN
authors.lastname: Chichkov
authors.forename: Inna
authors.initials: I
authors.lastname: Dumler
mesh_terms: D002450:Cell Communication; D002478:Cells, Cultured; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
chemical_list: D014568:Urokinase-Type Plasminogen Activator
keywords: focal adhesion; microstructured biomaterial.; urokinase receptor; vascular injury; vascular smooth muscle cell