Reversibly Sticking Metals and Graphite to Hydrogels and Tissues.

We have discovered that hard, electrical conductors (e.g., metals or graphite) can be adhered to soft, aqueous materials (e.g., hydrogels, fruit, or animal tissue) without the use of an adhesive. The adhesion is induced by a low DC electric field. As an example, when 5 V DC is applied to graphite slabs spanning a tall cylindrical gel of acrylamide (AAm), a strong adhesion develops between the anode (+) and the gel in about 3 min. This adhesion endures after the field is removed, and we term it as hard-soft electroadhesion or EA[HS]. Depending on the material, adhesion occurs at the anode (+), cathode (-), or both electrodes. In many cases, EA[HS] can be reversed by reapplying the field with reversed polarity. Adhesion via EA[HS] to AAm gels follows the electrochemical series: e.g., it occurs with copper, lead, and tin but not nickel, iron, or zinc. We show that EA[HS] arises via electrochemical reactions that generate chemical bonds between the electrode and the polymers in the gel. EA[HS] can create new hybrid materials, thus enabling applications in robotics, energy storage, and biomedical implants. Interestingly, EA[HS] can even be achieved underwater, where typical adhesives cannot be used.

A Smart Skin for Hydrogels That Enables Switchable Solute Release.

Many applications of hydrogels rely on their ability to deliver encapsulated solutes, such as drugs; however, small hydrophilic solutes rapidly leak out of gels by diffusion. A need exists for a way to regulate solute release out of gels─to ensure zero release until a desired time (the OFF state) and thereafter for the release to be switched ON at a high rate. This should ideally be a repeatable switch; i.e., the gel should be cyclable repeatedly between the ON and OFF states. Such perfect, cyclical ON-OFF release of solutes from gels is demonstrated for the first time through a "smart skin" that is synthesized rapidly (in ∼10 min) around an entire gel. The thin (∼100 µm) and transparent polymer skin is endowed with redox-responsive properties through the use of urethane and acrylate monomers, one of which contains a thioether group. Initially, the skin is hydrophobic (water contact angle 102°), and it completely prevents hydrophilic solutes from leaking out of the gel. When contacted with oxidants such as hydrogen peroxide (H2O2), the thioethers are converted to sulfoxides, making the skin hydrophilic (water contact angle 42°) and thereby turning ON the release of solutes. Conversely, solute release can be turned OFF subsequently by adding a reducing agent such as vitamin C that reverts the sulfoxides to thioethers and thus returns the skin to its hydrophobic state. The release rate in the ON state can be tuned via the skin thickness as well as the oxidant concentration. The ability to regulate solute delivery from gels using smart skins is likely to prove significant in areas ranging from separations to agriculture and drug delivery.

Cell-Like Capsules with "Smart" Compartments.

Eukaryotic cells have inner compartments (organelles), each with distinct properties and functions. One mimic of this architecture, based on biopolymers, is the multicompartment capsule (MCC). Here, MCCs in which the inner compartments are chemically unique and "smart," i.e., responsive to distinct stimuli in an orthogonal manner are created. Specifically, one compartment alone is induced to degrade when the MCC is contacted with an enzyme while other compartments remain unaffected. Similarly, just one compartment gets degraded upon contact with reactive oxygen species generated from hydrogen peroxide (H2 O2 ). And thirdly, one compartment alone is degraded by an external, physical stimulus, namely, by irradiating the MCC with ultraviolet (UV) light. All these specific responses are achieved without resorting to complicated chemistry to create the compartments: the multivalent cation used to crosslink the biopolymer alginate (Alg) is simply altered. Compartments of Alg crosslinked by Ca2+ are shown to be sensitive to enzymes (alginate lyases) but not to H2 O2 or UV, whereas the reverse is the case with Alg/Fe3+ compartments. These results imply the ability to selectively burst open a compartment in an MCC "on-demand" (i.e., as and when needed) and using biologically relevant stimuli. The results are then extended to a sequential degradation, where compartments in an MCC are degraded one after another, leaving behind an empty MCC lumen. Collectively, this work advances the MCC as a platform that not only emulates key features of cellular architecture, but can also begin to capture rudimentary cell-like behaviors.

Universal Way to "Glue" Capsules and Gels into 3D Structures by Electroadhesion.

We demonstrate the use of electroadhesion (EA), i.e., adhesion induced by an electric field, to connect a variety of soft materials into 3D structures. EA requires a cationic and an anionic material, but these can be of diverse origin, including covalently cross-linked hydrogels made by polymerizing charged monomers or physical gels/capsules formed by the ionic cross-linking of biopolymers (e.g., alginate and chitosan). Between each cationic/anionic pair, EA is induced rapidly (in ∼10 s) by low voltages (∼10 V DC)─and the adhesion is permanent after the field is turned off. The adhesion is strong enough to allow millimeter-scale capsules/gels to be assembled in 3D into robust structures such as capsule-capsule chains, capsule arrays on a base gel, and a 3D cube of capsules. EA-based assembly of spherical building blocks can be done more precisely, rapidly, and easily than by any alternative techniques. Moreover, the adhesion can be reversed (by switching the polarity of the field)─hence any errors during assembly can be undone and fixed. EA can also be used for selective sorting of charged soft matter─for example, a 'finger robot' can selectively 'pick up' capsules of the opposite charge by EA and subsequently 'drop off' these structures by reversing the polarity. Overall, our work shows how electric fields can be used to connect soft matter without the need for an adhesive or glue.

Chemically Fueled Dissipative Cross-Linking of Protein Hydrogels Mediated by Protein Unfolding.

Cells assemble dynamic protein-based nanostructures far from equilibrium, such as microtubules, in a process referred to as dissipative assembly. Synthetic analogues have utilized chemical fuels and reaction networks to form transient hydrogels and molecular assemblies from small molecule or synthetic polymer building blocks. Here, we demonstrate dissipative cross-linking of transient protein hydrogels using a redox cycle, which exhibit protein unfolding-dependent lifetimes and mechanical properties. Fast oxidation of cysteine groups on bovine serum albumin by hydrogen peroxide, the chemical fuel, formed transient hydrogels with disulfide bond cross-links that degraded over hours by a slow reductive back reaction. Interestingly, despite increased cross-linking, the hydrogel lifetime decreased as a function of increasing denaturant concentration. Experiments showed that the solvent-accessible cysteine concentration increased with increasing denaturant concentration due to unfolding of secondary structures. The increased cysteine concentration consumed more fuel, which led to less direction oxidation of the reducing agent and affected a shorter hydrogel lifetime. Increased hydrogel stiffness, disulfide cross-linking density, and decreased oxidation of redox-sensitive fluorescent probes at a high denaturant concentration provided evidence supporting the unveiling of additional cysteine cross-linking sites and more rapid consumption of hydrogen peroxide at higher denaturant concentrations. Taken together, the results indicate that the protein secondary structure mediated the transient hydrogel lifetime and mechanical properties by mediating the redox reactions, a feature unique to biomacromolecules that exhibit a higher order structure. While prior works have focused on the effects of the fuel concentration on dissipative assembly of non-biological molecules, this work demonstrates that the protein structure, even in nearly fully denatured proteins, can exert similar control over reaction kinetics, lifetime, and resulting mechanical properties of transient hydrogels.

Capsules with bacteria and fungi in distinct compartments: A platform for studying microbes from different kingdoms and their cross-communication.

Recently, we have created 'artificial cells' with an architecture mimicking that of typical eukaryotic cells. Our design uses common biopolymers like alginate and chitosan to create multi-compartment capsules (MCCs) via oil-free microfluidics. MCCs (~ 500 µm in diameter) can be engineered with multiple inner compartments, each with a distinct payload. This mimics the distinct organelles in eukaryotic cells, each of which has unique properties. In this study, we encapsulate microbial cells from two distinct kingdoms - Pseudomonas aeruginosa (bacteria) and Candida albicans (fungi) - in the inner compartments of MCCs. The two microbes are commonly found in biofilms at sites of infection in humans. We first demonstrate that the MCC can serve as a simple platform to observe the comparative growth of the cells in real time. Unlike typical co-culture in solution or on agar plates, the cells can grow in their own compartments without direct physical contact. Moreover, the hydrogel matrix in the compartments mimics the three-dimensional (3-D) environment that cells naturally encounter during their growth. Small molecules added to the solution are shown to permeate through the capsule walls and affect cell growth: for example, cationic surfactants inhibit the fungi but not the bacteria. Conversely, low pH and kanamycin inhibit the bacteria but not the fungi. Also, when the bacteria are present in adjacent compartments, the fungal cells mostly stay in a yeast morphology, meaning as spheroidal cells. In contrast, in the absence of the bacteria, the fungi transition into hyphae, i.e., long multicellular filaments. The inhibition of this morphological switch in fungal cells is shown to be induced by signaling molecules (specifically, the quorum sensing autoinducer-1 or AI-1) secreted by the bacteria. Thus, the MCC platform can also be used to detect cross-kingdom signaling between the compartmentalized microbes.

How a Gel Can Protect an Egg: A Flexible Hydrogel with Embedded Starch Particles Shields Fragile Objects Against Impact.

Hydrogels are networks of polymer chains that are swollen in water. In recent years, several routes have been devised to make hydrogels that are flexible and bendable. This work investigates whether such flexible gels can be wrapped around brittle or fragile objects (such as an egg or a fruit) and protect the objects against impact. We study gels made by either physical cross-linking (e.g., gelatin) or chemical cross-linking (e.g., acrylamide) and the same gels with various particulate additives. None of the bare gels are protective, and nanoparticles like iron oxide or silica do not help. However, the addition of starch granules to the above gels greatly enhances their protective abilities. When a load strikes a gelatin gel containing 20% starch, the peak impact force is reduced by 25% when compared to a bare gel without the starch. Correspondingly, the coefficient of restitution (COR) is also lowered by the presence of starch (i.e., a ball bounces less on a starch-bearing gel). We correlate the impact-absorbing effects of starch granules to their ability to shear-thicken water. When starch granules are gelatinized by heat, they no longer give rise to shear-thickening, and in turn, their protective ability in a gel is also eliminated. Our research can guide the rational design of protective coatings or armor for fragile objects, which could be applied in the sports, defense, and consumer sectors.

Transformation of Lipid Vesicles into Micelles by Adding Nonionic Surfactants: Elucidating the Structural Pathway and the Intermediate Structures.

The phospholipid lecithin (L) and the nonionic surfactant Tween 80 (T) are used together in various contexts, including in drug delivery and oil spill remediation. There is hence a need to elucidate the nanostructures in LT mixtures, which is the focus of this paper. We study these mixtures using cryogenic transmission electron microscopy (cryo-TEM), coupled with dynamic light scattering and small-angle neutron scattering. As the concentration of Tween 80 is increased, the vesicles formed by lecithin are transformed into spherical micelles. We identify bicelles (i.e., disc-like micelles) as well as cylindrical micelles as the key stable nanostructures formed at intermediate L/T ratios. The bicelles have diameters ∼13-26 nm, and the bicelle size decreases as the Tween 80 content increases. We propose that the lecithin lipids form the body of the discs, while the Tween 80 surfactants occupy the rims. This hypothesis is consistent with geometric arguments because lecithin is double-tailed and favors minimal curvature, whereas the single-tailed Tween 80 molecules prefer curved interfaces. In the case of cylindrical micelles, cryo-TEM reveals that the micelles are short (length < 22 nm) and flexible. We are able to directly visualize the microstructure of the aggregates formed by lecithin-Tween 80 mixtures, thereby enhancing the understanding of morphological changes in the lecithin-Tween 80 system.

Superfast-Expanding Porous Hydrogels: Pushing New Frontiers in Converting Chemical Potential into Useful Mechanical Work.

Superabsorbent polymer gels can absorb large amounts of water (100-1000× their dry weight). For the past 50 years, many scientists such as de Gennes have proposed to extract mechanical work from gel expansion/contraction, which could pave the way for "artificial muscles". However, slow rates of gel expansion have limited these efforts: macroscale (∼cm) gels take over 24 h to expand to their equilibrium size. Gels can be made to expand faster if their characteristic length scale is reduced, e.g., by making a macroscopic gel porous. Still, gels that are both superabsorbent and able to expand rapidly have not yet been realized. Here, we create gels at the macroscale (∼cm or larger) that are porous, highly robust, superabsorbent and expand much faster than any gels thus far. Our approach involves the in situ foaming of a monomer solution (acrylic acid and acrylamide) using a double-barreled syringe that has acid and base in its two barrels. Gas (CO2) is generated at the mixing tip of the syringe by the acid-base reaction, and gas bubbles are stabilized by an amphiphilic polymer in one of the barrels. The monomers are then polymerized by ultraviolet (UV) light to form the gel around the bubbles, and the material is dried under ambient conditions to give a porous solid. When this dry gel is added to water, it absorbs water at a rate of 20 g/g·s until an equilibrium is achieved at ∼300× its weight. In the process, each gel dimension increases by ∼20%/s until its final dimensions are more than 3× larger. Such rapid and appreciable expansion can be easily observed by the eye, and remarkably, the swollen gel is robust enough to be picked up by hand. SEM images reveal a porosity of >90% and an interconnected network of pores. The gels are responsive to pH, and a full cycle of expansion (in regular water) and contraction (at pH 10 or in ethanol) can be completed within about 60 s. We use gel expansion to rapidly lift weights against gravity, resulting in ∼0.4 mJ of work being done over 40 s, which translates to a power density of 260 mW/kg. This ability to harness the chemical potential energy from the gel to do useful mechanical work could enable new designs for mechano-chemical engines─and potentially for artificial muscles.

A Simple Way to Synthesize a Protective "Skin" around Any Hydrogel.

In nature, various structures such as fruits and vegetables have a water-rich core that is covered by a hydrophobic layer, i.e., their skin. The skin creates a barrier that prevents chemicals in the external environment from entering the core; at the same time, the skin also ensures that the water in the core is preserved and not lost by evaporation. Currently, for many applications involving hydrogels, especially in areas such as soft robotics or bioelectronic interfaces, it would be advantageous if the gel could be encased in a skin-like material. However, forming such a skin around a gel has proved challenging because the skin would need to be a hydrophobic material with a distinct chemistry from the hydrophilic gel core. Here, we present a simple solution to this problem, which allows any hydrogel of arbitrary composition and geometry to be encased by a thin, transparent "skin." Our synthesis technique involves an inside-out polymerization, where one component of the polymerization (the initiator) is present only in the gel core, while other components (the monomers) are present only in the external medium. Accordingly, a thin polymeric layer (∼10-100 µm in thickness) grows outward from the core, and the entire process can be completed in a few minutes. We show that the presence of the skin prevents the gel from swelling in water and also from drying in air. Likewise, hydrophilic solutes in the gel core are completely prevented by the skin from leaking out into the external solution, while harsh chemicals (e.g., acids, bases, and chelators) or harmful microbes are prevented from entering the gels. The properties of the skin are all tunable, including its thickness and its mechanical properties. When the monomer used is urethane diacrylate, the resulting polyurethane skin is elastomeric, transparent, and peelable from the core gel. Conversely, when polyethylene glycol dimethacrylate is used as the monomer, the skin is hard and brittle (glass-like). The ability to grow a skin readily around any given hydrogel is likely to prove useful in numerous applications, such as in maintaining the electrical functionality of gel-based wires or circuit elements.

Reversible electroadhesion of hydrogels to animal tissues for suture-less repair of cuts or tears.

Electroadhesion, i.e., adhesion induced by an electric field, occurs between non-sticky cationic and anionic hydrogels. Here, we demonstrate electroadhesion between cationic gels and animal (bovine) tissues. When gel and tissue are placed under an electric field (DC, 10 V) for 20 s, the pair strongly adhere, and the adhesion persists indefinitely thereafter. Applying the DC field with reversed polarity eliminates the adhesion. Electroadhesion works with the aorta, cornea, lung, and cartilage. We demonstrate the use of electroadhesion to seal cuts or tears in tissues or model anionic gels. Electroadhered gel-patches provide a robust seal over openings in bovine aorta, and a gel sleeve is able to rejoin pieces of a severed gel tube. These studies raise the possibility of using electroadhesion in surgery while obviating the need for sutures. Advantages include the ability to achieve adhesion on-command, and moreover the ability to reverse this adhesion in case of error.

Spontaneous Formation of Stable Vesicles and Vesicle Gels in Polar Organic Solvents.

The self-assembly of lipids into nanoscale vesicles (liposomes) is routinely accomplished in water. However, reports of similar vesicles in polar organic solvents like glycerol, formamide, and ethylene glycol (EG) are scarce. Here, we demonstrate the formation of nanoscale vesicles in glycerol, formamide, and EG using the common phospholipid lecithin (derived from soy). The samples we study are simple binary mixtures of lecithin and the solvent, with no additional cosurfactants or salt. Lecithin dissolves readily in the solvents and spontaneously gives rise to viscous fluids at low lipid concentrations (∼2-4%), with structures ∼200 nm detected by dynamic light scattering. At higher concentrations (>10%), lecithin forms clear gels that are strongly birefringent at rest. Dynamic rheology confirms the elastic response of gels, with their elastic modulus being ∼20 Pa at ∼10% lipid. Images from cryo-scanning electron microscopy (cryo-SEM) indicate that concentrated samples are "vesicle gels," where multilamellar vesicles (MLVs, also called "onions"), with diameters between 50 and 600 nm, are close-packed across the sample volume. This structure can explain both the elastic rheology as well as the static birefringence of the samples. The discovery of vesicles and vesicle gels in polar solvents widens the scope of systems that can be created by self-assembly. Interestingly, it is much easier to form vesicles in polar solvents than in water, and the former are stable indefinitely, whereas the latter tend to aggregate or coalesce over time. The stability is attributed to refractive index-matching between lipid bilayers and the solvents, i.e., these vesicles are relatively "invisible" and thus experience only weak attractions. The ability to use lipids (which are "green" or eco-friendly molecules derived from renewable natural sources) to thicken and form gels in polar solvents could also prove useful in a variety of areas, including cosmetics, pharmaceuticals, and lubricants.

Using Microemulsion Phase Behavior as a Predictive Model for Lecithin-Tween 80 Marine Oil Dispersant Effectiveness.

Marine oil dispersants typically contain blends of surfactants dissolved in solvents. When introduced to the crude oil-seawater interface, dispersants facilitate the breakup of crude oil into droplets that can disperse in the water column. Recently, questions about the environmental persistence and toxicity of commercial dispersants have led to the development of "greener" dispersants consisting solely of food-grade surfactants such as l-α-phosphatidylcholine (lecithin, L) and polyoxyethylenated sorbitan monooleate (Tween 80, T). Individually, neither L nor T is effective at dispersing crude oil, but mixtures of the two (LT blends) work synergistically to ensure effective dispersion. The reasons for this synergy remain unexplained. More broadly, an unresolved challenge is to be able to predict whether a given surfactant (or a blend) can serve as an effective dispersant. Herein, we investigate whether the LT dispersant effectiveness can be correlated with thermodynamic phase behavior in model systems. Specifically, we study ternary "DOW" systems comprising LT dispersant (D) + a model oil (hexadecane, O) + synthetic seawater (W), with the D formulation being systematically varied (across 0:100, 20:80, 40:60, 60:40, 80:20, and 100:0 L:T weight ratios). We find that the most effective LT dispersants (60:40 and 80:20 L:T) induce broad Winsor III microemulsion regions in the DOW phase diagrams (Winsor III implies that the microemulsion coexists with aqueous and oil phases). This correlation is generally consistent with expectations from hydrophilic-lipophilic deviation (HLD) calculations, but specific exceptions are seen. This study then outlines a protocol that allows the phase behavior to be observed on short time scales (ca. hours) and provides a set of guidelines to interpret the results. The complementary use of HLD calculations and the outlined fast protocol are expected to be used as a predictive model for effective dispersant blends, providing a tool to guide the efficient formulation of future marine oil dispersants.

Phase-Selective Gelation of the Water Phase in an Oil-Water Mixture: An Approach Based on Oil-Activated Nanoparticle Assembly in Water.

Phase-selective gelation refers to the selective gelation of one phase in an immiscible mixture. Thus far, all such examples have involved a molecular gelator forming nanofibers in (and thus gelling) the oil phase in an oil/water mixture. Here, for the first time, we report the counterpart to the above phenomenon, i.e., selective gelation of the water phase in an oil/water mixture (while leaving the oil undisturbed). This has been a challenging problem because moieties that gel water tend to be either amphiphilic or oil-soluble; thus, if combined with an oil/water mixture, they invariably form an emulsion. Our approach solves this problem by exploiting the tunable self-assembly of laponite (LAP) nanoparticles. Initially, LAP nanoparticles (25 nm disks) are dispersed in water, where they remain unaggregated due to the steric stabilization provided by a triblock copolymer (Pluronic P123) adsorbed on their surface. Thus, the dispersion is initially a low-viscosity sol. When an immiscible oil such as hexadecane is introduced above the sol, the mixture remains biphasic, and both phases remain unaffected. Next, an organic acid such as butanoic acid (BA) is added to the oil. The BA is oil-soluble but also has limited solubility in the water. Over about 30 min, some of the BA enters the water, whereupon it "activates" the self-assembly of LAP particles into a three-dimensional "house-of-cards" network. Ultimately, the water phase is converted into a homogeneous gel with a sufficient yield stress: the aqueous gel holds its weight in the inverted vial while the oil phase remains a thin liquid that can be poured out of the vial. On the whole, the concept advanced here is about activating nanoparticle assembly in water through an adjacent, immiscible phase. This concept could prove useful in conducting certain separations or reactions in the laboratory as well as in enhanced oil recovery.

Multilayer tubes that constrict, dilate, and curl in response to stimuli.

Tubular structures in nature have the ability to respond to their environment-for example, blood vessels can constrict or dilate, thereby regulating flow velocity and blood pressure. These tubes have multiple concentric layers, with each layer having a distinct composition and properties. Inspired by such natural structures, we have synthesized responsive multilayer tubes in the laboratory without resorting to complex equipment such as a 3-D printer. Each layer of our tubes is a polymer gel formed by free-radical polymerization of water-soluble monomers. We can precisely control the inner diameter of the tube, the number of layers in the tube wall, and the thickness and chemistry of each layer. Tubes synthesized in this manner are robust, flexible, and stretchable. Moreover, our technique allows us to incorporate stimuli-responsive polymers into distinct regions of these tubes, and the resulting tubes can change their shape in response to external stimuli such as pH or temperature. In the case of laterally patterned tubes, the tube can be made to constrict or dilate over a particular segment-a behavior that is reminiscent of blood vessels. In the case of longitudinally patterned tubes, a straight tube can be induced to systematically curl into a coil. The versatility of our technique is further shown by constructing complex tubular architectures, including branched networks. On the whole, the polymeric tubes shown in this paper exhibit remarkable properties that cannot be realized by other techniques. Such tubes could find utility in biomedical engineering to construct anatomically realistic mimics of various tissues.

Single-Step Synthesis of Alginate Microgels Enveloped with a Covalent Polymeric Shell: A Simple Way to Protect Encapsulated Cells.

Microgels of biopolymers such as alginate are widely used to encapsulate cells and other biological payloads. Alginate is an attractive material for cell encapsulation because it is nontoxic and convenient: spherical alginate gels are easily created by contacting aqueous droplets of sodium alginate with divalent cations such as Ca2+. Alginate chains in the gel become cross-linked by Ca2+ cations into a 3-D network. When alginate gels are placed in a buffer, however, the Ca2+ cross-links are eliminated by exchange with Na+, thereby weakening and degrading the gels. With time, encapsulated cells are released into the external solution. Here, we describe a simple solution to the above problem, which involves forming alginate gels enveloped by a thin shell of a covalently cross-linked gel. The shell is formed via free-radical polymerization using conventional monomers such as acrylamide (AAm) or acrylate derivatives, including polyethylene glycol diacrylate (PEGDA). The entire process is performed in a single step at room temperature (or 37 °C) under mild, aqueous conditions. It involves combining the alginate solution with a radical initiator, which is then introduced as droplets into a reservoir containing Ca2+ and monomers. Within minutes of either simple incubation or exposure to ultraviolet (UV) light, the droplets are converted into alginate-polymer microcapsules with a core of alginate and a shell of the polymer (AAm or PEGDA). The microcapsules are mechanically more robust than conventional alginate/Ca2+ microgels, and while the latter swell and degrade when placed in buffers or in chelators like sodium citrate, the former remain stable under all conditions. We encapsulate both bacteria and mammalian cells in these microcapsules and find that the cells remain viable and functional over time. Lastly, a variation of the synthesis technique is shown to generate multilayered microcapsules with a liquid core surrounded by concentric layers of alginate and AAm gels. We anticipate that the approaches presented here will find application in a variety of areas including cell therapies, artificial cells, drug delivery, and tissue engineering.

Foams with Enhanced Rheology for Stopping Bleeding.

Bleeding from injuries to the torso region is a leading cause of fatalities in the military and in young adults. Such bleeding cannot be stopped by applying direct pressure (compression) of a bandage. An alternative is to introduce a foam at the injury site, with the expansion of the foam counteracting the bleeding. Foams with an active hemostatic agent have been tested for this purpose, but the barrier created by these foams is generally not strong enough to resist blood flow. In this paper, we introduce a new class of foams with enhanced rheological properties that enable them to form a more effective barrier to blood loss. These aqueous foams are delivered out of a double-barrelled syringe by combining precursors that produce bubbles of gas (CO2) in situ. In addition, one barrel contains a cationic polymer (hydrophobically modified chitosan, hmC) and the other an anionic polymer (hydrophobically modified alginate, hmA). Both these polymers function as hemostatic agents due to their ability to connect blood cells into networks. The amphiphilic nature of these polymers also enables them to stabilize gas bubbles without the need for additional surfactants. hmC-hmA foams have a mousse-like texture and exhibit a high modulus and yield stress. Their properties are attributed to the binding of hmC and hmA chains (via electrostatic and hydrophobic interactions) to form a coacervate around the gas bubbles. Rheological studies are used to contrast the improved rheology of hmC-hmA foams (where a coacervate arises) with those formed by hmC alone (where there is no such coacervate). Studies with animal wound models also confirm that the hmC-hmA foams are more effective at curtailing bleeding than the hmC foams due to their greater mechanical integrity.

Surface-modified nanoerythrosomes for potential optical imaging diagnostics.

Nanoerythrosomes (NERs), vesicle-like nanoparticles derived from red blood cells, represent a new and interesting vector for therapeutic molecules and imaging probes, mainly thanks to their high stability and excellent biocompatibility. Aiming to present a proof-of-concept of the use of NERs as diagnostic tools for in vitro/in vivo imaging purposes, we report here several functionalization routes to decorate the surfaces of NERs derived from bovine blood with two different fluorophores: 7-amino-4-methylcumarin and dibenzocyclooctinecyanine5.5. Notably, the fluorophores were cross-linked to the NERs surface with glutaraldehyde and, in the case of dibenzocyclooctinecyanine5.5, also using a click-chemistry route, termed strain-promoted azide-alkyne cycloaddition. The physicochemical characterization highlighted the high stability of the NERs derivatives in physiological conditions. Furthermore, the loading efficiency of the fluorophores on the NERs surface was evaluated using both UV-Vis spectroscopy and fluorescence microscopy.

Light-Triggered Rheological Changes in a System of Cationic Wormlike Micelles Formulated with a Photoacid Generator.

"Smart" fluids displaying large changes in their rheological properties in response to external stimuli have been of great interest in recent years. For example, "smart" wormlike micelles (WLMs) that respond to pH can be readily formulated by combining a cationic surfactant such as cetyltrimethylammonium bromide (CTAB) with an aromatic compound such as 1,2-dihydroxybenzene (DHB). Here, we show that a pH-responsive aqueous formulation as mentioned above can be simultaneously made responsive to ultraviolet (UV) light by incorporating a photoacid generator (PAG) into the system. A commercially available PAG, diphenyliodonium-2-carboxylate, is used here. Upon exposure to UV light, this PAG irreversibly photolyzes into iodobenzene (IB) and benzoic acid (BA), with the formation of BA, leading to a drop in pH. WLMs formed by mixtures of CTAB, DHB, and the PAG are systematically characterized before and after UV irradiation. As the PAG photolyzes, an increase in the viscosity of WLMs occurs by a factor of 1000. We show that the ratio of the zero-shear viscosity η0 (after UV/before UV) depends on the initial pH of the sample. The UV-induced increase in η0 can be attributed to the growth of WLMs in solution, which in turn is influenced by both the ionization state of DHB and the presence of IB and BA.

How Do Amphiphilic Biopolymers Gel Blood? An Investigation Using Optical Microscopy.

Amphiphilic biopolymers such as hydrophobically modified chitosan (hmC) have been shown to convert liquid blood into elastic gels. This interesting property could make hmC useful as a hemostatic agent in treating severe bleeding. The mechanism for blood gelling by hmC is believed to involve polymer-cell self-assembly, i.e., insertion of hydrophobic side chains from the polymer into the lipid bilayers of blood cells, thereby creating a network of cells bridged by hmC. Here, we probe the above mechanism by studying dilute mixtures of blood cells and hmC in situ using optical microscopy. Our results show that the presence of hydrophobic side chains on hmC induces significant clustering of blood cells. The extent of clustering is quantified from the images in terms of the area occupied by the 10 largest clusters. Clustering increases as the fraction of hydrophobic side chains increases; conversely, clustering is negligible in the case of the parent chitosan that lacks hydrophobes. Moreover, the longer the hydrophobic side chains, the greater the clustering (i.e., C12 > C10 > C8 > C6). Clustering is negligible at low hmC concentrations but becomes substantial above a certain threshold. Finally, clustering due to hmC can be reversed by adding the supramolecule α-cyclodextrin, which is known to capture hydrophobes in its binding pocket. Overall, the results from this work are broadly consistent with the earlier mechanism, albeit with a few modifications.