E. Johan Foster

Metastable supramolecular polymer nanoparticles via intramolecular collapse of single polymer chains.

We present an elegant approach for fabricating polymeric nanoparticles via the reversible noncovalent intramolecular cross-linking of single polymer chains. By protecting the well-studied 2-ureido-pyrimidinone moiety with an o-nitrobenzyl group, we have introduced a latent quadruple hydrogen bonding motif. Incorporating this group into linear poly(norbornenes) creates a class of supramolecular materials that can be readily dissolved and subsequently cross-linked upon irradiation with UV light, eliminating the need for selective solvent techniques. This is a facile method for producing well-defined particles with narrow polydispersity as confirmed by atomic force microscopy. By virtue of the nature of the intramolecular cross-linking (supramolecular interactions of pendant groups), these metastable nanoparticles are akin to folded biomacromolecules, representing the first step in linking synthetic polymers and self-folded biopolymers.

Isolation of Thermally Stable Cellulose Nanocrystals by Phosphoric Acid Hydrolysis

On account of their intriguing mechanical properties, low cost, and renewable nature, high-aspect-ratio cellulose nanocrystals (CNCs) are an attractive component for many nanomaterials. Due to hydrogen bonding between their surface hydroxyl groups, unmodified CNCs (H-CNCs) aggregate easily and are often difficult to disperse. It is shown here that on account of ionic repulsion between charged surface groups, slightly phosphorylated CNCs (P-CNCs, average dimensions 31 ± 14 × 316 ± 127 nm, surface charge density = 10.8 ± 2.7 mmol/kg cellulose), prepared by controlled hydrolysis of cotton with phosphoric acid, are readily dispersible and form stable dispersions in polar solvents such as water, dimethyl sulfoxide, and dimethylformamide. Thermogravimetric analyses reveal that these P-CNCs exhibit a much higher thermal stability than partially sulfated CNCs (S-CNCs), which are frequently employed, but suffer from limited thermal stability. Nanocomposites of an ethylene oxide-epichlorohydrin copolymer and H-CNCs, S-CNCs, and P-CNCs were prepared, and their mechanical properties were studied by dynamic mechanical thermal analysis. The results show that P-CNCs offer a reinforcing capability that is comparable to that of H-CNCs or S-CNCs.

Comparison of the Properties of Cellulose Nanocrystals and Cellulose Nanofibrils Isolated from Bacteria, Tunicate, and Wood Processed Using Acid, Enzymatic, Mechanical, and Oxidative Methods

This work describes the measurement and comparison of several important properties of native cellulose nanocrystals (CNCs) and cellulose nanofibrils (CNFs), such as crystallinity, morphology, aspect ratio, and surface chemistry. Measurement of the fundamental properties of seven different CNCs/CNFs, from raw material sources (bacterial, tunicate, and wood) using typical hydrolysis conditions (acid, enzymatic, mechanical, and 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO)-mediated oxidation), was accomplished using a variety of measurement methods. Atomic force microscopy (AFM), transmission electron microscopy (TEM), and 13C cross-polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR) spectroscopy were used to conclude that CNCs, which are rodlike in appearance, have a higher crystallinity than CNFs, which are fibrillar in appearance. CNC aspect ratio distributions were measured and ranged from 148±147 for tunicate-CNCs to 23±12 for wood-CNCs. Hydrophobic interactions, measured using inverse gas chromatography (IGC), were found to be an important contribution to the total surface energy of both types of cellulose. In all cases, a trace amount of naturally occurring fluorescent compounds was observed after hydrolysis. Confocal and Raman microscopy were used to confirm that the fluorescent species were unique for each cellulose source, and demonstrated that such methods can be useful for monitoring purity during CNC/CNF processing. This study reveals the broad, tunable, multidimensional material space in which CNCs and CNFs exist.

Investigating the interaction of cellulose nanofibers derived from cotton with a sophisticated 3D human lung cell coculture

Cellulose nanofibers are an attractive component of a broad range of nanomaterials. Their intriguing mechanical properties and low cost, as well as the renewable nature of cellulose make them an appealing alternative to carbon nanotubes (CNTs), which may pose a considerable health risk when inhaled. Little is known, however, concerning the potential toxicity of aerosolized cellulose nanofibers. Using a 3D in vitro triple cell coculture model of the human epithelial airway barrier, it was observed that cellulose nanofibers isolated from cotton (CCN) elicited a significantly (p < 0.05) lower cytotoxicity and (pro-)inflammatory response than multiwalled CNTs (MWCNTs) and crocidolite asbestos fibers (CAFs). Electron tomography analysis also revealed that the intracellular localization of CCNs is different from that of both MWCNTs and CAFs, indicating fundamental differences between each different nanofibre type in their interaction with the human lung cell coculture. Thus, the data shown in the present study highlights that not only the length and stiffness determine the potential detrimental (biological) effects of any nanofiber, but that the material used can significantly affect nanofiber-cell interactions.

Curcumin-releasing mechanically adaptive intracortical implants improve the proximal neuronal density and blood–brain barrier stability

The cellular and molecular mechanisms by which neuroinflammatory pathways respond to and propagate the reactive tissue response to intracortical microelectrodes remain active areas of research. We previously demonstrated that both the mechanical mismatch between rigid implants and the much softer brain tissue, as well as oxidative stress, contribute to the neurodegenerative reactive tissue response to intracortical implants. In this study, we utilize physiologically responsive, mechanically adaptive polymer implants based on poly(vinyl alcohol) (PVA), with the capability to also locally administer the antioxidant curcumin. The goal of this study is to investigate if the combination of two independently effective mechanisms - softening of the implant and antioxidant release - leads to synergistic effects in vivo. Over the first 4weeks of the implantation, curcumin-releasing, mechanically adaptive implants were associated with higher neuron survival and a more stable blood-brain barrier at the implant-tissue interface than the neat PVA controls. 12weeks post-implantation, the benefits of the curcumin release were lost, and both sets of compliant materials (with and without curcumin) had no statistically significant differences in neuronal density distribution profiles. Overall, however, the curcumin-releasing softening polymer implants cause minimal implant-mediated neuroinflammation, and embody the new concept of localized drug delivery from mechanically adaptive intracortical implants.

Biosensors Based on Porous Cellulose Nanocrystal–Poly(vinyl Alcohol) Scaffolds

Cellulose nanocrystals (CNCs), which offer a high aspect ratio, large specific surface area, and large number of reactive surface groups, are well suited for the facile immobilization of high density biological probes. We here report functional high surface area scaffolds based on cellulose nanocrystals (CNCs) and poly(vinyl alcohol) (PVA) and demonstrate that this platform is useful for fluorescence-based sensing schemes. Porous CNC/PVA nanocomposite films with a thickness of 25-70 nm were deposited on glass substrates by dip-coating with an aqueous mixture of the CNCs and PVA, and the porous nanostructure was fixated by heat treatment. In a subsequent step, a portion of the scaffolds hydroxyl surface groups was reacted with 2-(acryloxy)ethyl (3-isocyanato-4-methylphenyl)carbamate to permit the immobilization of thiolated fluorescein-substituted lysine, which was used as a first sensing motif, via nucleophile-based thiol-ene Michael addition. The resulting sensor films exhibit a nearly instantaneous and pronounced change of their fluorescence emission intensity in response to changes in pH. The approach was further extended to the detection of protease activity by immobilizing a Förster-type resonance energy transfer chromophore pair via a labile peptide sequence to the scaffold. This sensing scheme is based on the degradation of the protein linker in the presence of appropriate enzymes, which separate the chromophores and causes a turn-on of the originally quenched fluorescence. Using a standard benchtop spectrometer to monitor the increase in fluorescence intensity, trypsin was detected at a concentration of 250 μg/mL, i.e., in a concentration that is typical for abnormal proteolytic activity in wound fluids.

Shape-Memory Bionanocomposites Based on Chitin Nanocrystals and Thermoplastic Polyurethane with a Highly Crystalline Soft Segment

Shape-memory bionanocomposites based on a naturally sourced segmented thermoplastic polyurethane and chitin nanocrystals were synthesized, and their mechanical properties and thermally activated shape-memory behavior were studied. The chitin nanocrystals were incorporated during the synthesis of the prepolymer made from a castor oil-based difunctional polyol and hexamethylene diisocyanate. The polymerization was completed by addition of propanediol, as a corn-sugar based chain extender, bringing the weight content of components from renewable resources to >60%. Thermal analysis of the bionanocomposites revealed a phase-separated morphology, which is composed of soft and hard domains, which bestow the material with two melting transitions at 60 and 125 °C, that are exploitable for a shape memory effect. The soft segment is responsible for temporary shape fixing, while the hard segment crystallites are responsible for the permanent shape. The introduction of small amounts (0.25-2 wt %) of chitin nanocrystals was found to increase the crystallinity of the hard segment by way of nucleation, which in turn improves the shape recovery considerably. The thermally activated shape-memory behavior of the synthesized bionancomposites is exploitable with a programming and release temperature of 60 °C. The materials display good in vitro cell response, as shown by short-term cytotoxicity assays, and therefore, the bionanocomposites appear to be potentially useful for biomedical applications.

Isolation of cellulose nanocrystals from pseudostems of banana plants

On account of their excellent mechanical properties, cellulose nanocrystals (CNCs) are attracting significant interest as a naturally sourced, renewable and inexpensive component of a broad range of nanomaterials. CNCs can be extracted from virtually any natural cellulosic material, but characteristic properties such as maximum aspect ratio, crystal structure, and crystallinity vary considerably between sources. In this work, the isolation of CNCs from the pseudostems of banana plants was explored. The dried stems from the species musa sapientum linn were first cleaned by Soxhlet extraction, alkali treatment and bleaching and subsequently hydrolyzed to CNCs using sulfuric acid. The hydrolysis time was systematically varied, with the objective to maximize the length (L = 375 ± 100 nm) and aspect ratio (A = 28) of the resulting CNCs. The surface charge density of the CNCs thus isolated was 168 mmol kg−1, the predominant crystal structure was that of cellulose I, and the crystallinity was 74%. In order to elucidate the reinforcing capability of the new CNCs, nanocomposites with an ethylene oxide–epichlorohydrin copolymer were prepared and their mechanical properties were investigated by dynamic mechanical analysis (DMA). A comparison with reference nanocomposites made with CNCs isolated from cotton shows that the new CNCs display a higher reinforcing capability.

Self-assembly of hydrogen-bonded molecules: discotic and elliptical mesogens

The effect of hydrogen bonding on the phase behaviour of discotic mesogens was investigated with a series of dibenzophenazine carboxylic acids and their methyl ester analogues. The esters exhibit only columnar hexagonal phases, while the acids form columnar hexagonal, columnar rectangular and nematic mesophases. The acids have much higher transition temperatures and supercool to room temperature while maintaining the liquid crystalline ordering. These differences could be explained by the ability of the acids to form hydrogen-bonded dimers, which may also be regarded as supramolecular elliptically-shaped mesogens.

An in vitro testing strategy towards mimicking the inhalation of high aspect ratio nanoparticles

BackgroundThe challenge remains to reliably mimic human exposure to high aspect ratio nanoparticles (HARN) via inhalation. Sophisticated, multi-cellular in vitro models are a particular advantageous solution to this issue, especially when considering the need to provide realistic and efficient alternatives to invasive animal experimentation for HARN hazard assessment. By incorporating a systematic test-bed of material characterisation techniques, a specific air-liquid cell exposure system with real-time monitoring of the cell-delivered HARN dose in addition to key biochemical endpoints, here we demonstrate a successful approach towards investigation of the hazard of HARN aerosols in vitro.MethodsCellulose nanocrystals (CNCs) derived from cotton and tunicates, with differing aspect ratios (~9 and ~80), were employed as model HARN samples. Specifically, well-dispersed and characterised CNC suspensions were aerosolised using an “Air Liquid Interface Cell Exposure System” (ALICE) at realistic, cell-delivered concentrations ranging from 0.14 to 1.57 μg/cm2. The biological impact (cytotoxicity, oxidative stress levels and pro-inflammatory effects) of each HARN sample was then assessed using a 3D multi-cellular in vitro model of the human epithelial airway barrier at the air liquid interface (ALI) 24 hours post-exposure. Additionally, the testing strategy was validated using both crystalline quartz (DQ12) as a positive particulate control in the ALICE system and long fibre amosite asbestos (LFA) to confirm the susceptibility of the in vitro model to a fibrous insult.ResultsA rapid (≤4 min), controlled nebulisation of CNC suspensions enabled a dose-controlled and spatially homogeneous CNC deposition onto cells cultured under ALI conditions. Real-time monitoring of the cell-delivered CNC dose with a quartz crystal microbalance was accomplished. Independent of CNC aspect ratio, no significant cytotoxicity (p > 0.05), induction of oxidative stress, or (pro)-inflammatory responses were observed up to the highest concentration of 1.57 μg/cm2. Both DQ12 and LFA elicited a significant (p < 0.05) pro-inflammatory response at sub-lethal concentrations in vitro.ConclusionIn summary, whilst the present study highlights the benign nature of CNCs, it is the advanced technological and mechanistic approach presented that allows for a state of the art testing strategy to realistically and efficiently determine the in vitro hazard concerning inhalation exposure of HARN.