title: Growth Factor-Bearing Polymer Brushes--Versatile Bioactive Substrates Influencing Cell Response.
abstract: In this study we present the development of responsive nanoscale substrates exhibiting cell-guiding properties based on incorporated bioactive signaling cues. The investigative approach considered the effect of two different surface-bound growth factors (GFs) on cell behavior and response: hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF). Two surface biofunctionalization strategies were explored in order to conceive versatile, bioactive thin polymer brush films. Polymer brushes made of tethered poly(acrylic)acid (PAA) polymer layers with a high grafting density of polymer chains were biofunctionalized with GFs either by physisorption or chemisorption. Both GFs showed high binding efficiencies to PAA brushes based on their initial loading concentrations. The GF release kinetics can be distinguished depending on the applied biofunctionalization method. Specifically, a high initial burst followed by a constant slow release was observed in the case of both physisorbed HGF and bFGF. In contrast, the release kinetics of chemisorbed GFs were quite different. Remarkably, chemisorbed HGF remained bound to the brush surface for over 1 week, whereas 50% of chemisorbed bFGF was released slowly. Furthermore, the effect of these GF-biofunctionalized PAA brushes on different cells was investigated. A human hepatoma cell line (HepG2) was used to analyze the bioactivity of HGF-modified PAA brushes by measuring cell growth inhibition and scattering effects. Additionally, the differentiation of mouse embryonic stem cells (mESCs) toward endoderm was studied on bFGF-modified PAA brush surfaces. Finally, the results illustrate that PAA brushes, particularly those biofunctionalized with chemisorbed GFs, produce an expected measurable effect on both cell types. Therefore, PAA polymer brushes biofunctionalized with GFs can be used as bioactive cell culture substrates with tuned efficiency.
authors.affiliation: Leibniz Institute of Polymer Research Dresden , Hohe Strasse 6, 01069 Dresden, Germany.|Faculty of Science, Department of Chemistry, Chair of Physical Chemistry of Polymeric Materials, The Technische Universität Dresden , Bergstrasse 66, 01069 Dresden, Germany.
authors.forename: Evmorfia
authors.initials: E
authors.lastname: Psarra
authors.affiliation: Department of Biomedical Engineering, University of California at Davis , 451 East Health Sciences Drive, California 95616, United States.
authors.forename: Elena
authors.initials: E
authors.lastname: Foster
authors.affiliation: Leibniz Institute of Polymer Research Dresden , Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Ulla
authors.initials: U
authors.lastname: König
authors.affiliation: Department of Plant & Environmental New Resources, Kyung Hee University , Yongin-si, Gyeonggi-do 446-701, South Korea.
authors.forename: Jungmok
authors.initials: J
authors.lastname: You
authors.affiliation: Institute for Biomaterial Science Teltow, Helmholtz-Zentrum Geesthacht, Berlin-Brandenburg Center for Regenerative Therapies, Kantstrasse 55, 14513 Teltow, Germany.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Leibniz Institute of Polymer Research Dresden , Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Klaus-J
authors.initials: KJ
authors.lastname: Eichhorn
authors.affiliation: Leibniz Institute of Polymer Research Dresden , Hohe Strasse 6, 01069 Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Müller
authors.affiliation: Leibniz Institute of Polymer Research Dresden , Hohe Strasse 6, 01069 Dresden, Germany.|Faculty of Science, Department of Chemistry, Chair of Physical Chemistry of Polymeric Materials, The Technische Universität Dresden , Bergstrasse 66, 01069 Dresden, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Stamm
authors.affiliation: Department of Biomedical Engineering, University of California at Davis , 451 East Health Sciences Drive, California 95616, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Revzin
authors.affiliation: Leibniz Institute of Polymer Research Dresden , Hohe Strasse 6, 01069 Dresden, Germany.|Department of Chemistry, Hamilton Hall, University of Nebraska-Lincoln , 639 North 12th Street, Lincoln, Nebraska 68588, United States.
authors.forename: Petra
authors.initials: P
authors.lastname: Uhlmann
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry*; D056945:Hep G2 Cells; D017228:Hepatocyte Growth Factor / Q000737:chemistry*; D006801:Humans; D051379:Mice; D049329:Nanostructures / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D013379:Substrate Specificity; D013499:Surface Properties
chemical_list: D000180:Acrylic Resins; D011108:Polymers; D016222:Fibroblast Growth Factor 2; C006903:carbopol 940; D017228:Hepatocyte Growth Factor