One-Reactant Photografting of ATRP Initiators for Surface-Initiated Polymerization.

Self-initiated photografting polymerization is used to couple the polymerizable initiator monomer 2-(2-chloropropanoyloxy)ethyl acrylate to a range of polymeric substrates. The technique requires only UV light to couple the initiator to surfaces. The initiator surface density can be varied by inclusion of a diluent monomer or via selection of initiator and irradiation parameters. The functionality of the initiator surface is demonstrated by subsequent surface-initiated atom transfer radical polymerization. Surfaces are characterized by x-ray photoelectron spectroscopy (XPS), ellipsometry, and atomic force microscopy (AFM), and UV-induced changes to the initiator are assessed by (1) H NMR and gel permeation chromatography (GPC). This is the first time this one-reactant one-step technique has been demonstrated for creating an initiator surface of variable density.

The Unexpected Advantages of Using D-Amino Acids for Peptide Self- Assembly into Nanostructured Hydrogels for Medicine.

Self-assembled peptide hydrogels have brought innovation to the medicinal field, not only as responsive biomaterials but also as nanostructured therapeutic agents or as smart drug delivery systems. D-amino acids are typically introduced to increase the peptide enzymatic stability. However, there are several reports of unexpected effects on peptide conformation, self-assembly behavior, cytotoxicity and even therapeutic activity. This mini-review discusses all the surprising twists of heterochiral self-assembled peptide hydrogels, and delineates emerging key findings to exploit all the benefits of D-amino acids in this novel medicinal area.

The Phe-Phe Motif for Peptide Self-Assembly in Nanomedicine.

Since its discovery, the Phe-Phe motif has gained in popularity as a minimalist building block to drive the self-assembly of short peptides and their analogues into nanostructures and hydrogels. Molecules based on the Phe-Phe motif have found a range of applications in nanomedicine, from drug delivery and biomaterials to new therapeutic paradigms. Here we discuss the various production methods for this class of compounds, and the characterization, nanomorphologies, and application of their self-assembled nanostructures. We include the most recent findings on their remarkable properties, which hold substantial promise for the creation of the next generation nanomedicines.

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 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.

Antibacterial activity studies of plasma polymerised cineole films.

Costs associated with bacterial infections in medical devices exceed $US 30 billion each year in the United States alone due to device revisions and patient treatment. Likewise, in 2012-2013, 126 surgical bacterial infections cost a single Australian state over $AUD 5 million. In the search for coatings that can prevent bacterial attachment and reduce medical and human costs, a number of studies have explored the application of antibacterial and anti-fungal essential oils. Traditionally the antibacterial properties of tea tree oils have been linked to their major component terpinen-4-ol, with little focus on the second component, 1,8-cineole. In this study we explore the antibacterial behaviour of solutions of cineole and demonstrate its ability to significantly reduce Escherichia coli viability in solution. However, one of the challenges with essential oils is their limited reactivity and solubility, creating a significant limitation for translating these antibacterial oils into coatings for medical devices. Previous studies have shown that plasma polymerised thin films can be produced from 1,8-cineole (ppCo), though it is unknown if the antibacterial activity can be retained. Herein, we report the behaviour of ppCo films when exposed to different solvents, and the interaction of these films with two bacteria (Escherichia coli and Staphylococcus aureus) commonly related to the failure of medical devices. While a reduction in bacterial attachment was observed onto both the ppCo film and the control hydrophobic surface, only the ppCo coatings resisted biofilm formation after 5 days of incubation with Escherichia coli. Additionally, ppCo films were shown to be non-adherent and non-cytotoxic to mammalian fibroblast. The combination of these two findings suggests that while the ppCo films retained part of the antimicrobial activity of the cineole oil, any leachables that may be released from the coating are also not cytotoxic or cell disruptive to mammalian cells. These coatings present a promising approach toward creating biocompatible antimicrobial coatings from Australian essential oils.

Nanotopographic surfaces with defined surface chemistries from amyloid fibril networks can control cell attachment.

We show for the first time the possibility of using networks of amyloid fibrils, adsorbed to solid supports and with plasma polymer coatings, for the fabrication of chemically homogeneous surfaces with well-defined nanoscale surface features reminiscent of the topography of the extracellular matrix. The robust nature of the fibrils allows them to withstand the plasma polymer deposition conditions used with no obvious deleterious effect, thus enabling the underlying fibril topography to be replicated at the polymer surface. This effect was seen despite the polymer coating thickness being an order of magnitude greater than the fibril network. The in vitro culture of fibroblast cells on these surfaces resulted in increased attachment and spreading compared to flat plasma polymer films with the same chemical composition. The demonstrated technique allows for the rapid and reproducible fabrication of substrates with nanoscale fibrous topography that we believe will have applications in the development of new biomaterials allowing, for example, the investigation of the effect of extracellular matrix mimicking nanoscale morphology on cellular phenotype.

SU-8 photolithography on reactive plasma thin-films: coated microwells for peptide display.

We have developed a technique to create 50µm-deep microwells coated with a reactive and robust thin film, which withstands photolithographic processing, and allows for subsequent chemical functionalisation with biological cues (i.e. peptides). First, plasma polymerisation of 1-bromopropane was used to generate a bromine-functionalised thin film (BrPP) on a substrate of silicon wafer. Second, an epoxy functionalised polymer UV photoresist, SU-8, was deposited and developed to create 50µm-deep patterned microwells that display the BrPP coating at their base. Third, amino acids or peptides were selectively attached to the bottom of the microwells through bromine displacement by an amine or thiol nucleophile. Each surface functionalisation step was monitored by XPS, AFM, and contact angle measurements. These functionalities were then used as linkers to immobilise enzymes (e.g. HRP), which retain activity at the end of the process as shown by a biochemical activity assay. Peptide promoters of cell attachment were also immobilised and their functionality was evaluated using an L929 fibroblast adhesion assay. In conclusion, this work describes an innovative combination of plasma thin film deposition and photolithography to create 50µm-deep functionalised microwells for peptide display in biological applications.

In vivo biostability of polyurethane-organosilicate nanocomposites.

Organically modified layered silicates were incorporated into a polyether soft-segment polyurethane to form composites of at least delaminated morphology. The primary organic modifier was a quaternary ammonium compound; however, one composite included an alternative amino undecanoic acid-modified silicate. The composites' biostability was assessed in an in vivo ovine model over a period of 6 weeks. Attenuated total reflectance-Fourier transform infrared analysis and semi-quantitative scanning electron microscopy image rating indicate a significant enhancement of the base polyurethane biostability with the inclusion of silicate at 3 wt.%. The potential effect at 15 wt.% was confounded by probable leaching of the quaternary ammonium compound affecting the tissue response. The amino undecanoic acid composite compared favourably with the quaternary ammonium compound composite of equivalent silicate loading, and offers the promise of a more favourable tissue response.

Photoinitiated alkyne-azide click and radical cross-linking reactions for the patterning of PEG hydrogels.

The photolithographical patterning of hydrogels based solely on the surface immobilization and cross-linking of alkyne-functionalized poly(ethylene glycol) (PEG-tetraalkyne) is described. Photogenerated radicals as well as UV absorption by a copper chelating ligand result in the photochemical redox reduction of Cu(II) to Cu(I). This catalyzes the alkyne-azide click reaction to graft the hydrogels onto an azide-functionalized plasma polymer (N(3)PP) film. The photogenerated radicals were also able to abstract hydrogen atoms from PEG-tetraalkyne to form poly(α-alkoxy) radicals. These radicals can initiate cross-linking by addition to the alkynes and intermolecular recombination to form the PEG hydrogels. Spatially controlling the two photoinitiated reactions by UV exposure through a photomask leads to surface patterned hydrogels, with thicknesses that were tunable from tens to several hundreds of nanometers. The patterned PEG hydrogels (ca. 60 µm wide lines) were capable of resisting the attachment of L929 mouse fibroblast cells, resulting in surfaces with spatially controlled cell attachment. The patterned hydrogel surface also demonstrated spatially resolved chemical functionality, as postsynthetic modification of the hydrogels was successfully carried out with azide-functionalized fluorescent dyes via subsequent alkyne-azide click reactions.