title: New stent surface materials: the impact of polymer-dependent interactions of human endothelial cells, smooth muscle cells, and platelets.
abstract: Despite the development of new coronary stent technologies, in-stent restenosis and stent thrombosis are still clinically relevant. Interactions of blood and tissue cells with the implanted material may represent an important cause of these side effects. We hypothesize material-dependent interaction of blood and tissue cells. The aim of this study is accordingly to investigate the impact of vascular endothelial cells, smooth muscle cells and platelets with various biodegradable polymers to identify a stent coating or platform material that demonstrates excellent endothelial-cell-supportive and non-thrombogenic properties. Human umbilical venous endothelial cells, human coronary arterial endothelial cells and human coronary arterial smooth muscle cells were cultivated on the surfaces of two established biostable polymers used for drug-eluting stents, namely poly(ethylene-co-vinylacetate) (PEVA) and poly(butyl methacrylate) (PBMA). We compared these polymers to new biodegradable polyesters poly(l-lactide) (PLLA), poly(3-hydroxybutyrate) (P(3HB)), poly(4-hydroxybutyrate) (P(4HB)) and a polymeric blend of PLLA/P(4HB) in a ratio of 78/22% (w/w). Biocompatibility tests were performed under static and dynamic conditions. Measurement of cell proliferation, viability, glycocalix width, eNOS and PECAM-1 mRNA expression revealed strong material dependency among the six polymer samples investigated. Only the polymeric blend of PLLA/P(4HB) achieved excellent endothelial markers of biocompatibility. Data show that PLLA and P(4HB) tend to a more thrombotic response, whereas the polymer blend is characterized by a lower thrombotic potential. These data demonstrate material-dependent endothelialization, smooth muscle cell growth and thrombogenicity. Although polymers such as PEVA and PBMA are already commonly used for vascular implants, they did not sufficiently meet the criteria for biocompatibility. The investigated biodegradable polymeric blend PLLA/P(4HB) evidently represents a promising material for vascular stents and stent coatings.
authors.affiliation: University of Greifswald, Clinic for Internal Medicine B, Sauerbruchstraße, D-17475 Greifswald, Germany. Electronic address: buschr@uni-greifswald.de.
authors.forename: Raila
authors.initials: R
authors.lastname: Busch
authors.affiliation: University of Greifswald, Clinic for Internal Medicine B, Sauerbruchstraße, D-17475 Greifswald, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Strohbach
authors.affiliation: University of Greifswald, Clinic for Internal Medicine B, Sauerbruchstraße, D-17475 Greifswald, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Rethfeldt
authors.affiliation: University of Greifswald, Clinic for Internal Medicine B, Sauerbruchstraße, D-17475 Greifswald, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Walz
authors.affiliation: University of Greifswald, Clinic for Internal Medicine B, Sauerbruchstraße, D-17475 Greifswald, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Busch
authors.affiliation: University of Rostock, Institute for Biomedical Engineering, Friedrich-Barnewitz-Strasse 4, D-18119 Rostock, Germany.
authors.forename: Svea
authors.initials: S
authors.lastname: Petersen
authors.affiliation: University of Greifswald, Clinic for Internal Medicine B, Sauerbruchstraße, D-17475 Greifswald, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Felix
authors.affiliation: University of Rostock, Institute for Biomedical Engineering, Friedrich-Barnewitz-Strasse 4, D-18119 Rostock, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Sternberg
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002450:Cell Communication / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D019276:Glycocalyx / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011108:Polymers / Q000494:pharmacology*; D012212:Rheology / Q000187:drug effects; D015607:Stents; D013314:Stress, Mechanical; D013499:Surface Properties
chemical_list: D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011108:Polymers; D052250:Nitric Oxide Synthase Type III
keywords: Biodegradable polymers; Endothelial cells; Platelets; Smooth muscle cells; Stents