Plasma polymerization for biomedical applications: A review

Plasma polymers have long been of interest as thin film coatings on biomedical devices and products, to generate desirable surface properties for favorable bio-interfacial interactions. Plasma polymers have also been used as platforms for the covalent immobilization of bioactive molecules. More recently, additional aspects have been investigated, such as selective prevention of adhesion of microbial pathogens, either via plasma polymers per se or including antimicrobial drugs. Plasma polymers have also been investigated for the release of silver ions and small organic molecules. Complementing low-pressure plasma approaches, processes at atmospheric pressure have attracted interest recently, including for nano/biocomposite coatings. This contribution reviews the use of plasma polymers for intended biomedical applications, with a focus on more recent topic areas

Surface grafting of electrospun fibers using ATRP and RAFT for the control of biointerfacial interactions

BACKGROUND The ability to present signalling molecules within a low fouling 3D environment that mimics the extracellular matrix is an important goal for a range of biomedical applications, both in vitro and in vivo. Cell responses can be triggered by non-specific protein interactions occurring on the surface of a biomaterial, which is an undesirable process when studying specific receptor-ligand interactions. It is therefore useful to present specific ligands of interest to cell surface receptors in a 3D environment that minimizes non-specific interactions with biomolecules, such as proteins. METHOD In this study, surface-initiated atom transfer radical polymerization (SI-ATRP) of poly(ethylene glycol)-based monomers was carried out from the surface of electrospun fibers composed of a styrene/vinylbenzyl chloride copolymer. Surface initiated radical addition-fragmentation chain transfer (SI-RAFT) polymerisation was also carried out to generate bottle brush copolymer coatings consisting of poly(acrylic acid) and poly(acrylamide). These were grown from surface trithiocarbonate groups generated from the chloromethyl styrene moieties existing in the original synthesised polymer. XPS was used to characterise the surface composition of the fibers after grafting and after coupling with fluorine functional XPS labels. RESULTS Bottle brush type coatings were able to be produced by ATRP which consisted of poly(ethylene glycol) methacrylate and a terminal alkyne-functionalised monomer. The ATRP coatings showed reduced non-specific protein adsorption, as a result of effective PEG incorporation and pendant alkynes groups existing as part of the brushes allowed for further conjugation of via azide-alkyne Huisgen 1,3-dipolar cycloaddition. In the case of RAFT, carboxylic acid moieties were effectively coupled to an amine label via amide bond formation. In each case XPS analysis demonstrated that covalent immobilisation had effectively taken place. CONCLUSION Overall, the studies presented an effective platform for the preparation of 3D scaffolds which contain effective conjugation sites for attachment of specific bioactive signals of interest, as well as actively reducing non-specific protein interactions.This research was supported by the Cooperative Research Centre for Polymers (CRCP)

One step ATRP initiator immobilization on surfaces leading to gradient-grafted polymer brushes

Published: April 30, 2014A method is described that allows potentially any surface to be functionalized covalently with atom transfer radical polymerization (ATRP) initiators derived from ethyl-2-bromoisobutyrl bromide in a single step. In addition, the initiator surface density was variable and tunable such that the thickness of polymer chain grafted from the surface varied greatly on the surfaces providing examples, across the surface of a substrate, of increased chain stretching due to the entropic nature of crowded polymer chains leading toward polymer brushes. An initiator gradient of increasing surface density was deposited by plasma copolymerization of an ATRP initiator (ethyl 2-bromoisobutyrate) and a non-ATRP reactive diluent molecule (ethanol). The deposited plasma polymer retained its chemical ability to surface-initiate polymerization reactions as exemplified by N,N'-dimethyl acrylamide and poly(ethylene glycol) methyl ether methacrylate polymerizations, illustrating linear and bottle-brush-like chains, respectively. A large variation in graft thickness was observed from the low to high chain-density side suggesting that chains were forced to stretch away from the surface interface--a consequence of entropic effects resulting from increased surface crowding. The tert-butyl bromide group of ethyl 2-bromoisobutyrate is a commonly used initiator in ATRP, so a method for covalent linkage to any substrate in a single step desirably simplifies the multistep surface activation procedures currently used.Bryan R. Coad, Katie E. Styan, and Laurence Meaghe

Antifungal coatings by caspofungin immobilization onto biomaterials surfaces via a plasma polymer interlayer

Published Online: 14 October 2015Not only bacteria but also fungal pathogens, particularly Candida species, can lead to biofilm infections on biomedical devices. By covalent grafting of the antifungal drug caspofungin, which targets the fungal cell wall, onto solid biomaterials, a surface layer can be created that might be able to provide long-term protection against fungal biofilm formation. Plasma polymerization of propionaldehyde (propanal) was used to deposit a thin (∼20 nm) interfacial bonding layer bearing aldehyde surface groups that can react with amine groups of caspofungin to form covalent interfacial bonds for immobilization. Surface analyses by x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed the intended grafting and uniformity of the coatings, and durability upon extended washing. Testing for fungal cell attachment and ensuing biofilm formation showed that caspofungin retained activity when covalently bound onto surfaces, disrupting colonizing Candida cells. Mammalian cytotoxicity studies using human primary fibroblasts indicated that the caspofungin-grafted surfaces were selective in eliminating fungal cells while allowing attachment and spreading of mammalian cells. These in vitro data suggest promise for use as antifungal coatings, for example, on catheters, and the use of a plasma polymer interlayer enables facile transfer of the coating method onto a wide variety of biomaterials and biomedical devices.Stefani S. Griesser, Marek Jasieniak, Bryan R. Coad, and Hans J. Griesse

Evaluation of entropic interaction chromatography media

Entropic interaction chromatography (EIC) media were synthesized by aqueous atom transfer radical polymerization (ATRP) of N,N -dimethylacrylamide (DMA) from the surfaces of non-porous and porous matrices. This novel chromatographic medium demonstrated efficient size-based separation of protein mixtures through the entropy change associated with solute partitioning into the layer of polymer attached to the support. Reaction conditions influencing the physical properties of the grafted layer were investigated. The use of "grafting from" initiators on a hydrolyzable ester linkage enabled exhaustive characterization of the grafted layer when cleaved from the surface. Negatively charged sulfate groups on the surface of the support were required for growth of dense polymer brushes and a combination of high surface charge and initiator concentration were necessary for the growth of dense brushes. The molecular weight of the grafts could be controlled by modifying the concentration of DMA used for the polymerization. Low polydispersities for the grafted layer demonstrated that the polymerization was well controlled. Scale up permitted the targeted synthesis of sufficient material grafted with 55.7 kDa grafts of high density (0.164±0.005 chains/nm ²) to be packed into a 30 x 1 cm chromatography column. Evaluation of a wide variety of columns synthesized with varying graft molecular weights or densities revealed that by exercising synthetic control over physical properties of the grafted layer, the selectivity curve could be tuned. Reducing the graft density allowed greater partitioning of high molecular weight solutes, extending the linear range of the selectivity curve. Increasing the graft molecular weight also altered selectivity, but more directly affected column capacity by increasing the volume of the grafted layer. Through the use of modeling studies, it was predicted that the shear force could act to reduce the number of conformations available to chains, increasing their rigidity without significantly altering the thickness of the grafted layer. A reduction in protein partitioning predicted by this situation was observed experimentally. The large scale EIC column has potential application towards rapid desalting applications of bimolecular feeds and the ease by which graft properties can be tuned suggests that the synthesis of custom chromatography media may be possible.Science, Faculty ofChemistry, Department ofGraduat

ToF-SIMS multivariate analysis of surface-grafted small bioactive molecules

In the development of bioactive coatings on biomaterials, it is essential to characterize the successful fabrication and the uniformity of intended coatings by sensitive surface analytical techniques, so as to ensure reliable interpretation of observed biointerfacial responses. This can, however, be challenging when small bioactive molecules are grafted onto biomaterials surfaces at sub- and near-monolayer densities. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides the required sensitivity, but ion signals from small grafted molecules may still be dominated by fragment ions from the underlying polymer. In such cases, multivariate analysis provides valuable enhancement of spectral data, as illustrated here by examples comprising the surface grafting of bioactive serrulatane molecules, the peptide GRGDSP, the oligonucleotide 15-thymidine, and the antifungal compound Amphotericin B. The authors also show how ToF-SIMS plus principal component analysis can distinguish between covalent grafting and physisorption of the antibiotics caspofungin and micafungin.Marek Jasieniak, Bryan R. Coad and Hans J. Griesser

Polymer Brush Gradients Grafted from Plasma-Polymerized Surfaces

A new method for generating a surface density gradient of polymer chains is presented. A substrate-independent polymer deposition technique was used to coat materials with a chemical gradient based on plasma copolymerization of 1,7-octadiene and allylamine. This provided a uniform chemical gradient to which initiators for atom transfer radical polymerization (ATRP) were immobilized. After surface-initiated atom transfer radical polymerization (SI-ATRP), poly­(2-hydroxyethyl methacrylate) (PHEMA) chains were grafted from the surface and the measured thickness profiles provided direct evidence for how surface crowding provides an entropic driving force resulting in chain extension away from the surface. Film thicknesses were found to increase with the position along the gradient surface, reflecting the gradual transition from collapsed to more extended surface-tethered polymer chains as the grafting density increased. The method described is novel in that the approach provides covalent linkages from the polymer coating to the substrate and is not limited to a particular surface chemistry of the starting material

One Step ATRP Initiator Immobilization on Surfaces Leading to Gradient-Grafted Polymer Brushes

A method is described that allows potentially any surface to be functionalized covalently with atom transfer radical polymerization (ATRP) initiators derived from ethyl-2-bromoisobutyrl bromide in a single step. In addition, the initiator surface density was variable and tunable such that the thickness of polymer chain grafted from the surface varied greatly on the surfaces providing examples, across the surface of a substrate, of increased chain stretching due to the entropic nature of crowded polymer chains leading toward polymer brushes. An initiator gradient of increasing surface density was deposited by plasma copolymerization of an ATRP initiator (ethyl 2-bromoisobutyrate) and a non-ATRP reactive diluent molecule (ethanol). The deposited plasma polymer retained its chemical ability to surface-initiate polymerization reactions as exemplified by <i>N</i>,<i>N</i>′-dimethyl acrylamide and poly­(ethylene glycol) methyl ether methacrylate polymerizations, illustrating linear and bottle-brush-like chains, respectively. A large variation in graft thickness was observed from the low to high chain-density side suggesting that chains were forced to stretch away from the surface interfacea consequence of entropic effects resulting from increased surface crowding. The <i>tert</i>-butyl bromide group of ethyl 2-bromoisobutyrate is a commonly used initiator in ATRP, so a method for covalent linkage to any substrate in a single step desirably simplifies the multistep surface activation procedures currently used