Plasma polymer gradients : developing a tool for the screening of biological responses to surfaces

Controlling the interaction of cells with a material surface is of major interest in the field of biomedical material science. Plasma polymers are an attractive way to modify the surface chemistry of a material because this technique is versatile and can be applied to a wide range of different surfaces. The aim of the present work is to prepare a new chemical gradient tool using plasma polymerisation and assess its ability to provoke position dependent cell-surface interactions. A novel diffusion based approach is used to develop gradients from hydrophobic hexane (ppHex) to more hydrophilic allylamine (ppAAm) plasma polymers. The surface of the gradient and that of uniform control samples is characterised using WCA, XPS, ToF-SIMS and AFM. This data shows that the most distinct gradient was found in the wettability profile which can be controlled by changing the size of the opening through which diffusion of depositing species from the plasma occurs. The mechanism of the gradient formation is studied with channels of well defined cross sections. The deposition rate obtained on these samples shows a sharp drop off in the amount of ppHex deposited from the plasma starting 2 mm in advance of the opening. An estimation of the sheath dimensions indicates that this corresponds to the sheath thickness. It is suggested that plasma deposition through small openings such as pores depends on the relative dimensions of the sheath and the pore cross section. Inside the channels, oligomer formation is observed in the gas phase, presumably following a nucleophilic addition reaction mechanism. To study the stability of these plasma polymer surfaces in physiological conditions, surface analysis is also carried out on samples exposed to aqueous solutions. Some changes in the topography of the plasma polymer films are found. Most notably, uniform samples of ppHex deposited on top of ppAAm show the formation of blisters that are not observed on other samples. It is argued that these blisters are the result of water penetrating through the top ppHex layer and interacting with the more hydrophilic ppAAm or glass substrate. 3T3 fibroblasts cultured on the gradients show a gradual increase in cell density. This cell density gradient can be related linearly to the wettability gradient on the surface with non-linear relationships being observed with other surface parameters such as the ppHex thickness. The cell number on uniform ppAAm is much greater than on the ppAAm side of the gradient. Data from experiments with non-proliferating 3T3 fibroblasts indicates that the differences between the gradient and uniform ppAAm as well as the cell density increase along the gradient have their origin in a different number of cells adhered to the surface within the first 24 hours of cell culture. The adsorption of albumin and fibronectin on the plasma polymers demonstrate that displacement of the former by the latter takes place on the surface when adsorbed competitively. However, this displacement does not occur in different extents along the gradient surface, suggesting that protein displacement can not explain the increase in cell density towards the ppAAm end of the gradient

Interface and surface analysis for pharmaceutical applications: challenges and recent advances

Innovation in R&D is a key target for the pharmaceutical sector to address some of the challenges it currently faces. This review discusses these challenges in the context of pharmaceutically relevant surfaces and interfaces. The surface properties of materials determine many pharmaceutically important interactions and can be drastically different from the material’s bulk properties. We first introduce current challenges in the surface and interface analysis of pharmaceutical materials in the context of material design, administration and fabrication. We then review recent scientific and technological advances aimed to address these issues and discuss examples that illustrate the capabilities of these techniques

Interface and surface analysis for pharmaceutical applications: challenges and recent advances

Innovation in R&D is a key target for the pharmaceutical sector to address some of the challenges it currently faces. This review discusses these challenges in the context of pharmaceutically relevant surfaces and interfaces. The surface properties of materials determine many pharmaceutically important interactions and can be drastically different from the material’s bulk properties. We first introduce current challenges in the surface and interface analysis of pharmaceutical materials in the context of material design, administration and fabrication. We then review recent scientific and technological advances aimed to address these issues and discuss examples that illustrate the capabilities of these techniques

Selective modification of Ti6Al4V surfaces for biomedical applications

The surface of a medical implant is required to interact favourably with ions, biomolecules and cells in vivo, commonly resulting in the formation of the extracellular matrix. Medical grade Ti6Al4V alloy is widely used in orthopaedic and dental applications for bone replacement due to its advantageous mechanical properties and biocompatibility, which enhances the adhesion between native tissue and the implanted material. In this study, chemical and thermal modification of a medical-grade Ti6Al4V alloy were performed to enhance electrostatic interactions at the alloy surface with a synthetic peptide, suitable for conferring drug release capabilities and antimicrobial properties. The modified surfaces exhibited a range of topographies and chemical compositions depending primarily on the treatment temperature. The surface wetting behaviour was found to be pH-dependent, as were the adhesive properties, evidenced by chemical force titration atomic force microscopy

Optimizing pentacene growth in low-voltage organic thin-film transistors prepared by dry fabrication techniques

We have studied the effect of pentacene purity and evaporation rate on low-voltage organic thin-film transistors (OTFTs) prepared solely by dry fabrication techniques. The maximum field-effect mobility of 0.07 cm2/Vs was achieved for the highest pentacene evaporation rate of 0.32 Å/s and four-time purified pentacene. Four-time purified pentacene also led to the lowest threshold voltage of -1.1 V and inverse subthreshold slope of ~100 mV/decade. In addition, pentacene surface was imaged using atomic force microscopy, and the transistor channel and contact resistances for various pentacene evaporation rates were extracted and compared to field-effect mobilities

Processing and interpretation of core-electron XPS spectra of complex plasma-treated polyethylene-based surfaces using a theoretical peak model

Interpretation of X-ray photoelectron spectroscopy (XPS) spectra of complex material surfaces, such as those obtained after surface plasma treatment of polymers, is confined by the available references. The limited understanding of the chemical surface composition may impact the ability to determine suitable coupling chemistries used for surface decoration or assess surface-related properties like biocompatibility. In this work, XPS is used to investigate the chemical composition of various ultra-high-molecular-weight polyethylene (UHMWPE) surfaces. UHMWPE doped with α-tocopherol or functionalised by active screen plasma nitriding (ASPN) was investigated as a model system. Subsequently, a more complex combined system obtained by ASPN treatment of α-tocopherol doped UHMWPE was investigated. Through ab initio orbital calculations and by employing Koopmans' theorem, the core-electron binding energies (CEBEs) were evaluated for a substantial number of possible chemical functionalities positioned on PE-based model structures. The calculated ΔCEBEs showed to be in reasonable agreement with experimental reference data. The calculated ΔCEBEs were used to develop a material-specific peak model suitable for the interpretation of merged high-resolution C 1s, N 1s and O 1s XPS spectra of PE-based materials. In contrast to conventional peak fitting, the presented approach allowed the distinction of functionality positioning (i.e. centred or end-chain) and evaluation of the long-range effects of the chemical functionalities on the PE carbon backbone. Altogether, a more detailed interpretation of the modified UHMWPE surfaces was achieved whilst reducing the need for manual input and personal bias introduced by the spectral analyst

Cooperative self-assembly of peptide gelators and proteins

Molecular self-assembly provides a versatile route for the production of nanoscale materials for medical and technological applications. Herein, we demonstrate that the cooperative self-assembly of amphiphilic small molecules and proteins can have drastic effects on supramolecular nanostructuring of resulting materials. We report that mesoscale, fractal-like clusters of proteins form at concentrations that are orders of magnitude lower compared to those usually associated with molecular crowding at room temperature. These protein clusters have pronounced effects on the molecular self-assembly of aromatic peptide amphiphiles (fluorenylmethoxycarbonyl- dipeptides), resulting in a reversal of chiral organization and enhanced order through templating and binding. Moreover, the morphological and mechanical properties of the resultant nanostructured gels can be controlled by the cooperative self-assembly of peptides and protein fractal clusters, having implications for biomedical applications where proteins and peptides are both present. In addition, fundamental insights into cooperative interplay of molecular interactions and confinement by clusters of chiral macromolecules is relevant to gaining understanding of the molecular mechanisms of relevance to the origin of life and development of synthetic mimics of living systems

3D chemical characterization of frozen hydrated hydrogels using ToF-SIMS with argon cluster sputter depth profiling

Hydrogels have been used extensively in bioengineering as artificial cell culture supports. Investigation of the interrelationship between cellular response to the hydrogel and its chemistry ideally requires methods that allow characterization without labels and can map species in three dimensional to follow biomolecules adsorbed to, and absorbed into, the open structure before and during culture. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) has the potential to be utilized for through thickness characterization of hydrogels. The authors have established a simple sample preparation procedure to successfully achieve analysis of frozen hydrated hydrogels using ToF-SIMS without the need for dry glove box entry equipment. They demonstrate this on a poly(2-hydroxyethyl methacrylate) (pHEMA) film where a model protein (lysozyme) is incorporated using two methods to demonstrate how protein distribution can be determined. A comparison of lysozyme incorporation is made between the situation where the protein is present in a polymer dip coating solution and where lysozyme is in an aqueous medium in which the film is incubated. It is shown that protonated water clusters H(H2O)nþ where n ¼ 5–11 that are indicative of ice are detected through the entire thickness of the pHEMA. The lysozyme distribution through the pHEMA hydrogel films can be determined using the intensity of a characteristic amino acid secondary ion fragment

Analysis of enzyme-responsive peptide surfaces by Raman spectroscopy

We report on the use of Raman spectroscopy as a tool to characterise model peptide functionalised surfaces. By taking advantage of Raman reporters built into the peptide sequence, the enzymatic hydrolysis of these peptides could be determined

Low Molecular Weight Nucleoside Gelators: A Platform for Protein Aggregation Inhibition

© Copyright 2018 American Chemical Society. Low molecular weight nucleoside gelators hold great promise in drug delivery and particularly for the delivery of biologics because of their excellent biocompatibility. However, the influence of these gelators on protein aggregation inhibition has not yet been studied. Protein aggregation is the most significant cause of protein instability and can severely impact the biological activity of the protein, impairing the quality and safety of the formulation. Herein, we report the ability of a nucleoside-based gelator, N4-octanoyl-2′-deoxycytidine, to inhibit protein aggregation. Using turbidimetric, spectroscopic, and microscopic methods, we demonstrate that protein aggregation inhibition is dependent on gelator concentration. Moreover, we have found that the protein is still functionally active in the hydrogel