Molecular and Colloidal Transport in Bacterial Cellulose Hydrogels.

Bacterial cellulose biofilms are complex networks of strong interwoven nanofibers that control transport and protect bacterial colonies in the film. The design of diverse applications of these bacterial cellulose films also relies on understanding and controlling transport through the fiber mesh, and transport simulations of the films are most accurate when guided by experimental characterization of the structures and the resultant diffusion inside. Diffusion through such films is a function of their key microstructural length scales, determining how molecules, as well as particles and microorganisms, permeate them. We use microscopy to study the unique bacterial cellulose film via its pore structure and quantify the mobility dynamics of various sizes of tracer particles and macromolecules. Mobility is hindered within the films, as confinement and local movement strongly depend on the void size relative to diffusing tracers. The biofilms have a naturally periodic structure of alternating dense and porous layers of nanofiber mesh, and we tune the magnitude of the spacing via fermentation conditions. Micron-sized particles can diffuse through the porous layers but cannot penetrate the dense layers. Tracer mobility in the porous layers is isotropic, indicating a largely random pore structure there. Molecular diffusion through the whole film is only slightly reduced by the structural tortuosity. Knowledge of transport variations within bacterial cellulose networks can be used to guide the design of symbiotic cultures in these structures and enhance their use in applications like biomedical implants, wound dressings, lab-grown meat, clothing textiles, and sensors.

Crystal Comets: A Geometric Model for Sculpting Anisotropic Particles from Emulsions.

Microscopic high aspect ratio particles have many applications including enhanced delivery of active ingredients and food stability. Here, we develop a simple, scalable process that produces particles with a continuously controllable aspect ratio. Oil-in-water emulsion droplets are quenched and crystallize in the presence of surfactants that facilitate the ejection of the solid oil phase from its liquid precursor. Tuning the ejection and crystallization rates to be comparable, by adjusting the surfactant concentration and quench depth, promotes anisotropic particle growth by continuously ejecting solidified oil from the precursor droplet as the crystallization proceeds. We predict the accessible morphologies using an analytical geometric model that indicates a nonconstant contact angle during the crystallization process. We see that the crystal aspect ratio is dependent on the surfactant concentration, which can be explained as a variation of the maximum growth angle achieved during crystallization.

Aggregation in viscoelastic emulsion droplet gels with capillarity-driven rearrangements.

Arrested, or partial, coalescence of viscoelastic emulsion droplets can occur when elastic resistance to deformation offsets droplet surface area minimization. Arrest is a critical element of food and consumer product microstructure and performance, but direct studies of structural arrest and rearrangement have been carried out using only two or three droplets at a time. The question remains whether the behavior of small numbers of droplets also occurs in larger, more realistic many-droplet systems. Here we study two-dimensional aggregation and arrested coalescence of emulsions containing ∼1000 droplets and find that the restructuring mechanisms observed for smaller systems have a large effect on local packing in multidroplet aggregates, but surprisingly do not significantly alter overall mass scaling in the aggregates. Specifically, increased regions of hexagonal packing are observed as the droplet solids level, and thus elasticity, is decreased because greater degrees of capillary force-driven restructuring are possible. Diffusion-limited droplet aggregation simulations that account for the restructuring mechanisms agree with the experimental results and suggest a basis for prediction of larger-scale network properties and bulk emulsion behavior.

Correction: Comparison of bulk and microfluidic methods to monitor the phase behaviour of nanoparticles during digestion of lipid-based drug formulations using in situ X-ray scattering.

Correction for 'Comparison of bulk and microfluidic methods to monitor the phase behaviour of nanoparticles during digestion of lipid-based drug formulations using in situ X-ray scattering' by Ben J. Boyd et al., Soft Matter, 2019, 15, 9565-9578.

Soft Bacterial Cellulose Microcapsules with Adaptable Shapes.

Microcapsules with controlled stability and permeability are in high demand for applications in separation and encapsulation. We have developed a biointerfacial process to fabricate strong, but flexible, porous microcapsules from bacterial cellulose at an oil-water emulsion interface. A broad range of microcapsule sizes has been successfully produced, from 100 µm to 5 cm in diameter. The three-dimensional capsule microstructure was imaged using confocal microscopy, showing a cellulose membrane thickness of around 30 µm that is highly porous, with some pores larger than 0.5 µm that are permeable to most macromolecules by free diffusion but can exclude larger structures like bacteria. The mechanical deformation of cellulose microcapsules reveals their flexibility, enabling them to pass through constrictions with a much smaller diameter than their initial size by bending and folding. Our work provides a new approach for producing soft, permeable, and biocompatible microcapsules for substance encapsulation and protection. The capsules may offer a replacement for suspended polymer beads in commercial applications and could potentially act as a framework for artificial cells.

Comparison of bulk and microfluidic methods to monitor the phase behaviour of nanoparticles during digestion of lipid-based drug formulations using in situ X-ray scattering.

The performance of orally administered lipid-based drug formulations is crucially dependent on digestion, and understanding the colloidal structures formed during digestion is necessary for rational formulation design. Previous studies using the established bulk pH-stat approach (Hong et al. 2015), coupled to synchrotron small angle X-ray scattering (SAXS), have begun to shed light on this subject. Such studies of digestion using in situ SAXS measurements are complex and have limitations regarding the resolution of intermediate structures. Using a microfluidic device, the digestion of lipid systems may be monitored with far better control over the mixing of the components and the application of enzyme, thereby elucidating a finer understanding of the structural progression of these lipid systems. This work compares a simple T-junction microcapillary device and a custom-built microfluidic chip featuring hydrodynamic flow focusing, with an equivalent experiment with the full scale pH-stat approach. Both microfluidic devices were found to be suitable for in situ SAXS measurements in tracking the kinetics with improved time and signal sensitivity compared to other microfluidic devices studying similar lipid-based systems, and producing more consistent and controllable structural transformations. Particle sizing of the nanoparticles produced in the microfluidic devices were more consistent than the pH-stat approach.

Geometry and kinetics determine the microstructure in arrested coalescence of Pickering emulsion droplets.

Arrested coalescence occurs in Pickering emulsions where colloidal particles adsorbed on the surface of the droplets become crowded and inhibit both relaxation of the droplet shape and further coalescence. The resulting droplets have a nonuniform distribution of curvature and, depending on the initial coverage, may incorporate a region with negative Gaussian curvature around the neck that bridges the two droplets. Here, we resolve the relative influence of the curvature and the kinetic process of arrest on the microstructure of the final state. In the quasistatic case, defects are induced and distributed to screen the Gaussian curvature. Conversely, if the rate of area change per particle exceeds the diffusion constant of the particles, the evolving surface induces local solidification reminiscent of jamming fronts observed in other colloidal systems. In this regime, the final structure is shown to be strongly affected by the compressive history just prior to arrest, which can be predicted from the extrinsic geometry of the sequence of surfaces in contrast to the intrinsic geometry that governs the static regime.

Arrested Coalescence of Viscoelastic Droplets: Ellipsoid Shape Effects and Reorientation.

The stable configurations formed by two poroelastic, ellipsoid-shaped droplets during their arrested coalescence have been investigated using micromanipulation experiments. Ellipsoidal droplets are produced by millifluidic emulsification of petrolatum into a yield stress fluid that preserves their elongated shape. The liquid meniscus between droplets can transmit stress and instigate movement of the droplets, from their initial relative position, in order to minimize doublet surface energy. The action of the liquid meniscus causes the ellipsoidal droplets to undergo rolling and reorientation events because of their unique ellipsoid shape and associated variation in the surface curvature. The final configuration of the droplets is controlled by the balance between interfacial Laplace pressure and internal elasticity, as well as a constraint force that resists complete minimization of surface energy. Geometric and surface energy calculations are used to map the possible and most likely configurations of the droplet pairs. Experimental deviations from the calculations indicate the magnitude and potential origin of the constraint force resisting full equilibration. Droplet aspect ratio and elasticity are both shown to influence the degree of reorientation and stability of the droplets at energy extrema. Higher aspect ratios drive greater reorientation and better agreement with final doublet configurations predicted by energy minimization. Lower elasticity droplets undergo secondary deformations at high aspect ratios, further broadening the space of possible morphologies.

Model of Structured Emulsion Droplet Stability and Reconfigurability.

A model of internally structured emulsion droplets is presented that accounts for the traction forces generated by interfacial tension and the von Mises yield criterion of the internal supporting network. For symmetric droplets, the method calculates the total stress acting on a droplet locally, allowing droplet stability and location of failure to be predicted. It is not regions of high interfacial curvature that prompt droplet reconfiguration, rather regions transitioning from high to low curvature. The model enables the design of emulsion droplet response and reconfigurability to external triggers such as changes in surface tension (surfactant concentration) and temperature.

Comparing Surfactant Structures at "Soft" and "Hard" Hydrophobic Materials: Not All Interfaces Are Equivalent.

The interfacial structures of a range of amphiphilic molecules are studied with both "soft" and "hard" hydrophobic substrates. Neutron reflection and quartz crystal microbalance with dissipation measurements highlight the differences between the adsorbed structures adopted by sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (C16TAB), and the "AM1" surface active peptide. At the soft siloxane/water interface, small molecular surfactants form loosely packed layers, with the hydrophobic tails penetrating into the oily layer, and an area per surfactant molecule that is significantly less than previously reported for the air/water interface. Neutron reflection measurements, supported by quartz crystal microbalance studies, indicate that for C16TAB, approximately 30 ± 8% of the alkyl tail penetrates into the poly(dimethylsiloxane) (PDMS) layer, whereas 20 ± 5% of the alkyl tail of SDS is located in the PDMS. For the engineered peptide surfactant AM1 (21 residues), it was found that one face of the α helix penetrated into the PDMS film. In contrast, penetration of the surfactant tails was not observed against hard solidlike hydrophobic surfaces made from octadecyltrichlorosilane (OTS) for any of the molecular species studied. At the OTS/water interface, C16TAB and SDS were seen to adsorb as larger aggregates and not as monolayers. Amphiphilic adsorption (amount, structural conformation) at the PDMS/water interface is shown to be different from that at both the air/water interface and the hard OTS/water interface, illustrating that interfacial structures cannot be predicted by the surfactant packing parameter alone. The bound PDMS layer is shown to be a useful proxy for the oil/water interface in surface and stabilization studies, with hydrophobic components of the molecules able to penetrate into the oily PDMS.

Large Hexosomes from Emulsion Droplets: Particle Shape and Mesostructure Control.

Soft, rotationally symmetric particles of dispersed hexagonal liquid crystalline phase are produced using a method previously developed for cubosome microparticle production. The technique forms hexosome particles via removal of ethanol from emulsion droplets containing monoolein, water, and one of the various hydrophobic molecules: vitamin E, hexadecane, oleic acid, cyclohexane, or divinylbenzene. The unique rotational symmetry of the particles is characterized by optical microscopy and small-angle X-ray scattering to link particle phase, shape, and structure to composition. Rheology of the soft particles can be varied independently of shape, enabling control of transport, deformation, and biological response by controlling composition and molecular structure of the additives. The direct observations of formation, and the resultant hexosome shapes, link the particle-scale and mesoscale properties of these novel self-assembled particles and broaden their applications. The micron-scale hexosomes provide a route to understanding the effects of particle size, crystallization rate, and rheology on the production of soft particles with liquid crystalline structure and unique shape and symmetry.

Soft polyhedral particles based on cubic liquid crystalline emulsion droplets.

Soft polyhedral particles based on variations of the cubic symmetry group are produced from a precursor emulsion by extracting solvent to grow facets on the droplets. The droplets transform into liquid crystals with solid-like rheology and controlled size and shape. Small-angle X-ray scattering confirms a bicontinuous cubic liquid crystalline phase forms from aqueous glycerol monoolein and is responsible for the particle faceting observed. Different polyhedra are produced by varying face growth rates through control of precursor droplet size, system temperature, and solubilization and adsorption of guest molecules. More exotic faceted shapes can be formed by the soft particles by applying asymmetric solvent removal gradients and by deforming the precursor droplets into, for example, ellipsoids before crystallization. The method is a powerful means to produce soft polyhedra, using continuous microfluidic or other approaches, or to act as templates for hard polyhedral particle synthesis.

Arrested coalescence of viscoelastic droplets: triplet shape and restructuring.

The stability of shapes formed by three viscoelastic droplets during their arrested coalescence has been investigated using micromanipulation experiments. Addition of a third droplet to arrested droplet doublets is shown to be controlled by the balance between interfacial pressures driving coalescence and internal elasticity that resists total consolidation. The free fluid available within the droplets controls the transmission of stress during droplet combination and allows connections to occur via formation of a neck between the droplets. The anisotropy of three-droplet systems adds complexity to the symmetric case of two-droplet aggregates because of the multiplicity of orientations possible for the third droplet. When elasticity dominates, the initial orientation of the third droplet is preserved in the triplet's final shape. When elasticity is dominated by the interfacial driving force, the final shape can deviate strongly from the initial positioning of droplets. Movement of the third droplet to a more compact packing occurs, driven by liquid meniscus expansion that minimizes the surface energy of the triplet. A range of compositions and orientations are examined and the resulting domains of restructuring and stability are mapped based on the final triplet structure. A geometric and a physical model are used to explain the mechanism driving meniscus-induced restructuring and are related to the impact of these phenomena on multiple droplet emulsions.

Novel nano-cellulose excipient for generating non-Newtonian droplets for targeted nasal drug delivery.

PURPOSE: Thickening polymers have been used as excipients in nasal formulations to avoid nasal run-off (nasal drip) post-administration. However, increasing the viscosity of the formulation can have a negative impact on the quality of the aerosols generated. Therefore, the study aims to investigate the use of a novel smart nano-cellulose excipient to generate suitable droplets for nasal drug delivery that simultaneously has only marginally increased viscosity while still reducing nasal drips. METHODS: Nasal sprays containing nano-cellulose at different concentrations were investigated for the additive's potential as an excipient. The formulations were characterized for their rheological and aerosol properties. This was then compared to conventional nasal spray formulation containing the single-component hydroxyl-propyl methyl cellulose (HPMC) viscosity enhancing excipient. RESULTS: The HPMC-containing nasal formulations behave in a Newtonian manner while the nano-cellulose formulations have a yield stress and shear-thinning properties. At higher excipient concentrations and shear rates, the nano-cellulose solutions have significantly lower viscosities compared to the HPMC solution, resulting in improved droplet formation when actuated through conventional nasal spray. CONCLUSIONS: Nano-cellulose materials could potentially be used as a suitable excipient for nasal drug delivery, producing consistent aerosol droplet size, and enhanced residence time within the nasal cavity with reduced run-offs compared to conventional polymer thickeners.

Temperature-Induced Collapse, and Arrested Collapse, of Anisotropic Endoskeleton Droplets.

Micron-scale rod-shaped droplets with a range of aspect ratios are produced using extrusion of oil containing a soft wax crystal network to permit shape customization. A physical model of the droplet shape stability is developed based on balancing interfacial stresses with the internal crystal network yield stress. The model predicts the mechanical properties required for particular droplet size stability, in a given physicochemical environment, and is tested by microscopic observations of droplets over a range of relevant applied temperatures. The time-dependent response to temperature of individual rods is monitored and used to identify the collapse temperature based on structural yielding. Precise temperature control allows variation of the droplet endoskeleton yield stress and direct determination of the droplet stability as a function of size, by observing the onset of collapse by interfacial compression, and enables validation of the model predictions. Mapping the regions of droplet stability and instability for various-sized droplets yields a basis for designing droplet shapes for multiple applications using easily measured physical variables. The phenomenon of arrested collapse is also explored as a means of transforming simple rod-shaped starting materials into more complex shapes and enhancing adhesion to targeted solid surfaces, enabling exploitation of the hybrid solid-liquid nature of these droplets.

Synthesis of crosslinked polymeric nanocapsules using catanionic vesicle templates stabilized by compressed CO2.

The synthesis of polymeric nanocapsules in the approximate diameter range 40-100 nm (TEM/SEM) using catanionic surfactant vesicle templates stabilized by subcritical CO2 is demonstrated. Near equimolar aqueous solutions of the surfactants sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) experienced immediate vesicle destabilization and precipitation in the absence of CO2. However, pressurization with CO2 (5 MPa) dramatically enhanced the stability of the initial vesicles, and enabled swelling of the bilayers with hydrophobic monomers via diffusion loading (loading of monomers into preformed bilayers). Subsequent radical crosslinking polymerization of the monomers n-butyl methacrylate/tert-butyl methacrylate/ethylene glycol dimethacrylate contained within the bilayers was conducted at room temperature using UV-initiation under CO2 pressure. The hollow structure of the resultant nano-objects was confirmed by successful encapsulation and retention of the dye Nile Blue. It is demonstrated that using this method, polymeric nanocapsules can be successfully prepared using diffusion loading of up to 94 wt% monomer (rel. to surfactant) stabilized by CO2.

The role of curvature anisotropy in the ordering of spheres on an ellipsoid.

Non-spherical emulsion droplets can be stabilized by densely packed colloidal particles adsorbed at their surface. In order to understand the microstructure of these surface packings, the ordering of hard spheres on ellipsoidal surfaces is determined through large scale computer simulations. Defects in the packing are shown generically to occur most often in regions of strong curvature; however, the relationship between defects and curvature is nontrivial, and the distribution of defects shows secondary maxima for ellipsoids of sufficiently high aspect ratio. As with packings on spherical surfaces, additional defects beyond those required by topology are observed as chains or "scars". The transition point, however, is found to be softened by the anisotropic curvature which also partially orients the scars. A rich library of symmetric commensurate packings are identified for low particle number. We verify experimentally that ellipsoidal droplets of varying aspect ratio can be arrested by surface-adsorbed colloids.

Interfacial stability and shape change of anisotropic endoskeleton droplets.

The delivery of suspended active ingredients to a surface is a central function of numerous commercial cosmetic, drug, and agricultural formulations. Many products use liquid droplets as a delivery vehicle but, because interfacial tension keeps droplets spherical, these materials cannot exploit the benefits of anisotropic shape and shape change offered by solid colloids. In this work, individual droplet manipulation is used to produce viscoelastic droplets that can stably retain non-spherical shapes by balancing the Laplace pressure of the liquid-liquid interface with the elasticity of an internal crystalline network. A stability criterion is developed for idealized spherocylindrical droplets and shown to agree with experimental data for varying droplet size and rheology. Shape change can be induced in the anisotropic droplets by upsetting the balance of droplet interfacial tension and internal rheology. Using dilution to increase the interfacial tension shows that external stimuli can trigger collapse and shape change in these droplets. The droplets wrap around substrates during collapse, improving contact and adhesion. The model is used to develop design criteria for production of droplets with tunable response.

Deep Eutectic Solvent Eutectogels for Delivery of Broad-Spectrum Antimicrobials.

Gel-based wound dressings have gained popularity within the healthcare industry for the prevention and treatment of bacterial and fungal infections. Gels based on deep eutectic solvents (DESs), known as eutectogels, provide a promising alternative to hydrogels as they are non-volatile and highly tunable and can solubilize therapeutic agents, including those insoluble in hydrogels. A choline chloride:glycerol-cellulose eutectogel was loaded with numerous antimicrobial agents including silver nanoparticles, black phosphorus nanoflakes, and commercially available pharmaceuticals (octenidine dihydrochloride, tetracycline hydrochloride, and fluconazole). The eutectogels caused >97% growth reduction in Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa bacteria and the fungal species Candida albicans.

Propulsion, deformation, and confinement response of hollow nanocellulose millimotors.

HYPOTHESIS: Micromotor and nanomotor particles are typically made using dense solid particles that can sediment or be trapped in confined flow environments. Creation of much larger motors should be possible if a very low-density system is used with sufficient strength to carry liquid and still experience propulsive motion. Light, dense millimotors should also be able to deform more than dense solid ones in constrictions. EXPERIMENTS: Millimotors are created from permeable capsules of bacterial cellulose that are coated with catalse-containing metal-organic frameworks, enabling reactive propulsion in aqueous hydrogen peroxide. The motion of the motors is quantified using particle tracking and the deformation is measured using microcapillary compression and flow through confined channels. FINDINGS: Two different propulsion mechanisms are dominant depending on the motor surface chemistry: oxygen bubbles are expelled from hydrophilic millimotors, driving motion via recoil force and buoyancy. Hydrophobic millimotors remain attached to growing bubbles and move by buoyancy alone. Despite their large size, the low-density capsules compress to pass through contractions that would impede and be blocked by solid motors. The sparse structure but relatively large size of the motors enables them to transport significant volumes of liquid using minimal solid mass as a motor support structure.