RGD—Functionalized polymer brushes as substrates for the integrin specific adhesion of human umbilical vein endothelial cells

Tugulu, Stefano; Silacci, Paolo; Stergiopulos, Nikolaos; Klok, Harm‐Anton

doi:10.1016/j.biomaterials.2007.02.006

Cited by 252 publications

(273 citation statements)

References 40 publications

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“…22,35 The crosslinked nature of the brushes hampers cleavage and GPC analysis, which could enable to obtain information on the molecular weight of the surface grafted polymer chains and the grafting density of the polymer brush films. As a precise determination of the molecular weight and grafting density is not possible, the remainder of this manuscript will 14 use reaction time as a measure for the molecular weight of the surface grafted polymers and grafting densities will be expressed as a percentage, which indicates the volume % of the ATRP active organosilane 1 that was used to modify the silicon substrate (σ = 50, 75 and 100 %). RGD-functionalized polymer brushes were prepared by nitrophenylchloroformate (NPC) mediated post-polymerization modification of PHEMA, PPEGMA 6 and PPEGMA 10 brushes with σ = 100 % and different film thicknesses following an established protocol.…”

Section: Resultsmentioning

confidence: 99%

“…methacrylic acid 9,10,11 and zwitterionic monomers 12 ), 2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol) methacrylate (PEGMA) are particularly frequently employed as they allow access to polymer brush films that possess very efficient non-fouling properties and present side-chain functional hydroxyl groups, which provide a wide range of possibilities to introduce biochemical cues. 13,14,15,16 PHEMA and PPEGMA brushes will swell in aqueous media, which has important conseqences on the properties of these thin films. On the one hand, hydration, and, as a consequence, swelling, of these surface grafted polymer films is an important contributor to their ability to resist non-specific adhesion of proteins and cells.…”

Section: Introductionmentioning

confidence: 99%

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Swelling Behavior and Nanomechanical Properties of (Peptide-Modified) Poly(2-hydroxyethyl methacrylate) and Poly(poly(ethylene glycol) methacrylate) Brushes

et al. 2016

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Poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(poly(ethylene glycol) methacrylate) (PPEGMA) brushes represent a class of thin, surface-tethered polymer films that have been extensively used e.g. to generate non-biofouling surfaces or as model systems to study fundamental biointerfacial questions related to cell− surface interactions. As the properties of PHEMA and PPEGMA brushes depend on the hydration and swelling of these thin films, it is important to understand the influence of basic structural parameters such as the composition of the polymer brush, the film thickness, or grafting density on these phenomena. This article reports results of a series of experiments that were performed to investigate the swelling behavior and mechanical properties of a diverse library of PHEMA and PPEGMA brushes covering a range of film thicknesses and grafting densities. The swelling ratios of the PHEMA and PPEGMA brushes were determined by ellipsometry and neutron reflectivity experiments and ranged from ∼1.5 to ∼5.0. Decreasing the grafting density and decreasing the film thickness generally results in an increase in the swelling ratio. Modification of the PHEMA and PPEGMA brushes with the cell adhesive RGD peptide ligand was found to result in a decrease in the swelling ratio. The neutron reflectivity experiments further revealed that solvated PHEMA and PPEGMA brushes are best described by a two-layer model, consisting of a polymer-rich layer close to the substrate and a second layer that is swollen to a much higher degree at the brush−water interface.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Swelling Behavior and Nanomechanical Properties of (Peptide-Modified) Poly(2-hydroxyethyl methacrylate) and Poly(poly(ethylene glycol) methacrylate) Brushes

et al. 2016

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“…An attractive strategy to engineer the ECM-mimicking surface of synthetic functional materials is the use of polymer and such short peptide-epitopes, since polymeric materials can be easily engineered to have an appropriate mechanical strength, biocompatibility and stimuli-responsiveness. From these points of view, several types of peptide-containing block polymers have been developed as synthetic scaffolds for tissue engineering [6][7][8][9]. Thermo-responsive polymers with a lower critical solution temperature (LCST), such as poly(N-isopropylacrylamide) (PNIPAM), have also been used as functional surface especially in the field of cell-sheet engineering [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Fabrication of Thermo-Responsive Molecular Layers from Self-Assembling Elastin-Like Oligopeptides Containing Cell-Binding Domain for Tissue Engineering

et al. 2015

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Novel thermo-responsive elastin-like oligopeptides containing cell-binding epitope (Arg-Gly-Asp-Ser sequence); arginine-glycine-aspartic acid-serine (RGDS)-elastin-like peptides (ELP) and RGDS-deg-ELP; were newly prepared as building blocks of self-assembled molecular layer for artificial extra cellular matrix. A detailed analysis of the conformation of the oligo(ELP)s in water and their self-assembling behavior onto hydrophobic surfaces were performed by using circular dichroism, Fourier transform infrared spectroscopy (FTIR), atomic force microscopy and water contact angle measurements. The experimental results revealed that both oligo(ELP)s self-assembled onto hydrophobic surfaces and formed molecular layers based on their thermo-responsive conformational change from hydrous random coil to dehydrated β-turn structure. Effective cell adhesion and spreading behaviors were observed on these self-assembled oligo(ELP) layers. In addition, attached cells were found to be recovered successfully as a cell-sheet by temperature-induced disassembly of oligo(ELP) layer. This achievement provides an important insight to construct novel oligopeptide-based nano-surfaces for the design of smart artificial extra-cellular matrix. OPEN ACCESSPolymers 2015, 7 135

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“…13,14 Self-assembled monolayers and grafting from brushes are ultrathin and well defined, so that introduction of functional groups such as cell adhesion peptides can be controlled precisely. 15,16 In contrast, hydrogel films are three dimensionally cross-linked polymer networks with thicknesses ranging from few nanometers to several micrometers. Embedded functional groups may thus be located near the surface or in the volume of the gels.…”

Section: Introductionmentioning

confidence: 99%

Quantifying ligand–cell interactions and determination of the surface concentrations of ligands on hydrogel films: The measurement challenge

et al. 2015

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Hydrogels are extensively studied for biomaterials application as they provide water swollen noninteracting matrices in which specific binding motifs and enzyme-sensitive degradation sites can be incorporated to tailor cell adhesion, proliferation, and migration. Hydrogels also serve as excellent basis for surface modification of biomaterials where interfacial characteristics are decisive for implant success or failure. However, the three-dimensional nature of hydrogels makes it hard to distinguish between the bioactive ligand density at the hydrogel-cell interface that is able to interact with cells and the ligands that are immobilized inside the hydrogel and not accessible for cells. Here, the authors compare x-ray photoelectron spectrometry (XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), enzyme linked immunosorbent assay (ELISA), and the correlation with quantitative cell adhesion using primary human dermal fibroblasts (HDF) to gain insight into ligand distribution. The authors show that although XPS provides the most useful quantitative analysis, it lacks the sensitivity to measure biologically meaningful concentrations of ligands. However, ToF-SIMS is able to access this range provided that there are clearly distinguishable secondary ions and a calibration method is found. Detection by ELISA appears to be sensitive to the ligand density on the surface that is necessary to mediate cell adhesion, but the upper limit of detection coincides closely with the minimal ligand spacing required to support cell proliferation. Radioactive measurements and ELISAs were performed on amine reactive well plates as true 2D surfaces to estimate the ligand density necessary to allow cell adhesion onto hydrogel films. Optimal ligand spacing for HDF adhesion and proliferation on ultrathin hydrogel films was determined as 6.5 ± 1.5 nm.

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RGD—Functionalized polymer brushes as substrates for the integrin specific adhesion of human umbilical vein endothelial cells

Cited by 252 publications

References 40 publications

Swelling Behavior and Nanomechanical Properties of (Peptide-Modified) Poly(2-hydroxyethyl methacrylate) and Poly(poly(ethylene glycol) methacrylate) Brushes

Swelling Behavior and Nanomechanical Properties of (Peptide-Modified) Poly(2-hydroxyethyl methacrylate) and Poly(poly(ethylene glycol) methacrylate) Brushes

Fabrication of Thermo-Responsive Molecular Layers from Self-Assembling Elastin-Like Oligopeptides Containing Cell-Binding Domain for Tissue Engineering

Quantifying ligand–cell interactions and determination of the surface concentrations of ligands on hydrogel films: The measurement challenge

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