Search

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.

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.

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.

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.

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.

The two-tailed anionic surfactant, AOT is well-known to form spherical reverse micelles in organic solvents such as cyclohexane and n-alkanes. Here, we report that trace amounts (e.g., around 1 mM) of the dihydroxy bile salt, sodium deoxycholate (SDC) can transform these dilute micellar solutions into self-supporting, transparent organogels. Gels can be obtained at a total AOT + SDC concentration as low as 6 mM or about 2 mg mL−1. Among all the bile salts studied, SDC is the only one that is capable of inducing organogels. The structure and rheology of these organogels is reminiscent of the self-assembled networks formed by proteins such as actin in water. In particular, both classes of gels exhibit the remarkable property of strain-stiffening, where the gel stiffness (modulus) increases with strain amplitude. Structurally, both gels are based on entangled networks of long, cylindrical filaments. We propose that SDC forms hydrogen bonds with AOT headgroups, transforming some of the spherical AOT micelles into semiflexible filaments. The average diameter of these filaments has been measured by small-angle neutron scattering (SANS), and suggests that SDC molecules are stacked together in the filament core.

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.

We describe batch generation of uniform multifunctional chitosan microparticles for isolation of rare cells, such as circulating tumor cells (CTCs), from a sample of whole blood. The chitosan microparticles were produced in large numbers using a simple and inexpensive microtubing arrangement. The particles were functionalized through encapsulation of carbon black, to control autofluorescence, and surface attachment of streptavidin, to enable interactions with biotinylated antibodies. These large custom modified microparticles (≈164 μm diameter) were then packed into a microfluidic channel to demonstrate their utility in rare cell capture. Blood spiked with breast cancer (MCF-7) cells was first treated with a biotinylated antibody (anti-EpCAM, which is selective for cancer cells like MCF-7) and then pumped through the device. In the process, the cancer cells were selectively bound to the microparticles through non-covalent streptavidin–biotin interactions. The number density of captured cells was determined by fluorescence microscopy at physiologically relevant levels. Selective capture of the MCF-7 cells was characterized, and compared favorably with previous approaches. The overall approach using custom synthesized microparticles is versatile, and can allow researchers more flexibility for rare cell capture through simpler and cheaper methods than are currently employed.

Li-S batteries have been considered promising candidates for the next-generation energy storage devices because of their extremely high energy densities and low cost. However, Li dendrite formation/dissolution and shuttle of high-order polysulfides prevent their practical applications. Herein, we demonstrate a highly concentrated electrolyte, 12 M lithium bis(fluorosulfonyl)imide (LiFSI) salt in DME solvent (12 M LiFSI/DME), that can effectively suppress both the Li dendritic growth on the anode and the polysulfide shuttle reactions on the cathode side. The highly concentrated electrolyte along with the robust solid electrolyte interphase (SEI) formed therein play the key role in achieving high coulombic efficiencies for both Li stripping/plating (> 99.2%) and S cathode (> 99.7%). Based on the in-depth understanding of the interactions between electrodes and highly concentrated electrolyte, we designed a novel dilute electrolyte (1 M LiFSI/HFE + DME), which achieves similar electrochemical performances in Li-S batteries as the concentrated electrolytes. These Li-S batteries with the highest CE for Li anode and sulfur cathode maintains a high reversible capacity of 786 mA h/g at 0.1 A/g after 300 cycles, or 644 mA h/g at 300th cycle even at 1 A/g without any detectable shuttle reactions.

Background Currently, the standard of care for treating severe hemorrhage in a military setting is Combat Gauze (CG). Previous work has shown that hydrophobically modified chitosan (hm-C) has significant hemostatic capability relative to its native chitosan counterpart. This work aims to evaluate gauze coated in hm-C relative to CG as well as ChitoGauze (ChG) in a lethal in vivo hemorrhage model. Methods Twelve Yorkshire swine were randomized to receive either hm-C gauze ( n = 4), ChG ( n = 4), or CG ( n = 4). A standard hemorrhage model was used in which animals underwent a splenectomy before a 6-mm punch arterial puncture of the femoral artery. Thirty seconds of free bleeding was allowed before dressings were applied and compressed for 3 min. Baseline mean arterial pressure was preserved via fluid resuscitation. Experiments were conducted for 3 h after which any surviving animal was euthanized. Results hm-C gauze was found to be at least equivalent to both CG and ChG in terms of overall survival (100% versus 75%), number of dressing used (6 versus 7), and duration of hemostasis (3 h versus 2.25 h). Total post-treatment blood loss was lower in the hm-C gauze treatment group (4.7 mL/kg) when compared to CG (13.4 mL/kg) and ChG (12.1 mL/kg) groups. Conclusions hm-C gauze outperformed both CG and ChG in a lethal hemorrhage model but without statistical significance for key endpoints. Future comparison of hm-C gauze to CG and ChG will be performed on a hypothermic, coagulopathic model that should allow for outcome significance to be differentiated under small treatment groups.

Wormlike micelles (WLMs) formed from surfactants have attracted much attention for their ability to thicken water in a manner similar to water-soluble polymers. It is known that WLMs are cylindrical filaments that can attain very long contour lengths (∼few μm), akin to chains of polymers with ultra-high molecular weights (UHMWs). In this study, we aim to make a direct comparison between the thickening capabilities of WLMs and UHMW polymers. The chosen surfactant is erucyl dimethyl amidopropyl betaine (EDAB), a C22-tailed zwitterionic surfactant known to form particularly long WLMs independent of salt. The chosen polymer is nonionic polyacrylamide (PAM) having an UHMW of 12 MDa. Both EDAB WLMs and the PAM show strong thickening capability in saline water at 25 °C, but the WLMs are more efficient. For example, a 1.0 wt% EDAB WLM sample has a similar zero-shear viscosity η0 (∼40 000 mPa s) to a 2.5 wt% PAM solution. When temperature is increased, both samples show an exponential reduction in viscosity, but the WLMs are more sensitive to temperature. Microstructural differences between the two systems are confirmed by data from small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). As expected, the key differences are that the WLM chains have a larger core radius (Rcore) and in turn, a longer persistence length (lp) than the PAM chains.

Hydrogels with shapes that can be adapted to their environment have attracted great attention from both academia and industry. We report herein a new and robust strategy to reprogram the light-induced shape transformation of a thermoresponsive composite hydrogel sheet with erasable and rewritable patterns of iron oxide nanoparticles as photothermal agents. Numerous distinct and reversible shape transformations are achieved from a single hydrogel sheet by repeatably writing in the sheet with different nanoparticle patterns. The shape transformations were verified by finite element modeling. The present strategy is simple, fast, and efficient in reprogramming the shape change of the thermoresponsive hydrogel material. The composite hydrogel sheet may find applications in soft robotics, tissue engineering, and controlled release.

We demonstrate the use of electric fields to rapidly form gels of the biopolymer alginate (Alg) in specific three-dimensional (3-D) shapes and patterns. In our approach, we start with a gel of the biopolymer agarose, which is thermoresponsive and hence can be molded into a specific shape. The agarose mold is then loaded with Ca2+ cations and placed in a beaker containing an Alg solution. The inner surface of the beaker is surrounded by aluminum foil (cathode), and a copper wire (anode) is stuck in the agarose mold. These are connected to a direct current (DC) power source, and when a potential of ∼10 V is applied, an Alg gel is formed in a shape that replicates the mold. Gelation occurs because the Ca2+ ions electrophoretically migrate away from the mold, whereupon they cross-link the Alg chains adjacent to the mold. At low Ca2+ (0.01 wt %), the Alg gel layer grows outward from the mold surface at a steady rate of about 0.8 mm/min, and the gel stops growing when the field is switched off. After a gel of d...

Wormlike micelles (WLMs) are long, flexible cylindrical chains formed by the self-assembly of surfactants in semidilute solutions. Scientists have been fascinated by WLMs because of their similarities to polymers, while at the same time, the viscoelastic properties of WLM solutions have made them useful in a variety of industrial applications. To date, most studies on WLMs have been performed in water (i.e., a highly polar liquid), while there are a few examples of "reverse" WLMs in oils (i.e., highly nonpolar liquids). However, in organic solvents with lower polarity than water such as glycerol, formamide, and ethylene glycol, there have been no reports of WLMs thus far. Here, we show that it is indeed possible to induce a long-tailed cationic surfactant to assemble into WLMs in several of these solvents. To form WLMs, the surfactant is combined with a "binding" salt, i.e., one with a large organic counterion that is capable of binding to the micelles. Examples of such salts include sodium salicylate and sodium tosylate, and we find self-assembly to be maximized when the surfactant and salt concentrations are near-equimolar. Interestingly, the addition of a simple, inorganic salt such as sodium chloride (NaCl) to the same surfactant does not induce WLMs in polar solvents (although it does so in water). Thus, the design rules for WLM formation in polar solvents are distinct from those in water. Aqueous WLMs have been characterized at temperatures from 25 °C and above, but few studies have examined WLMs at much lower (e.g., subzero) temperatures. Here, we have selected a surfactant with a very low Krafft point (i.e., the surfactant does not crystallize out of solution upon cooling due to a cis-unsaturation in its tail) and a low-freezing solvent, viz. a 90/10 mixture of glycerol and ethylene glycol. In these mixtures, we find evidence for WLMs that persist down to temperatures as low as -20 °C. Rheological techniques as well as small-angle neutron scattering (SANS) have been used to characterize the WLMs under these conditions. Much like their aqueous counterparts, WLMs in polar solvents show viscoelastic properties, and accordingly, these fluids could find applications as synthetic lubricants or as improved antifreezing fluids.

A simple amphiphile, N-cardanyltaurine amide (NCT) with different degrees of cis-unsaturation in its tail resulted in the formation of strong organogels. Interestingly, this is in contrast to the commonly accepted notion that introducing unsaturation in alkyl chains enhances fluidity in lipid assemblies. The physico-chemical and first-principles DFT calculations confirmed the pegging of ‘kinked’ unsaturated side chains, where the hydrophobic interlocking as in Velcro fasteners leads to a network of cylindrical micelles, resulting in self-standing organogels. Textural profile analysis and spectroscopic details substantiated the dynamic assembly to resemble a 3D network of gelators rather than being a cross-linked or polymerized matrix of monomers.

A 53-year-old woman is admitted with a serum creatinine of 16 mg/dl. Seven months earlier, she was diagnosed with heart failure and started on several medications, including Hydralazine. Laboratory studies revealed the presence of dual Anti-Neutrophil Cytoplasmic Antibodies (anti-MPO and anti-PR3), anti-nuclear and anti-histone antibodies. The clinical diagnosis was Drug-Induced ANCA Vasculitis (DIAV). Kidney histology, however, did not reveal crescents, but showed characteristic features of Alport’s syndrome.

We have developed microscale polymer capsules that are able to chemically degrade a certain type of polymeric microbead in their immediate vicinity. The inspiration here is from the body’s immune system, where killer T cells selectively destroy cancerous cells or cells infected by pathogens while leaving healthy cells alone. The “killer” capsules are made from the cationic biopolymer chitosan by a combination of ionic cross-linking (using multivalent tripolyposphate anions) and subsequent covalent cross-linking (using glutaraldehyde). During capsule formation, the enzyme glucose oxidase (GOx) is encapsulated in these capsules. The target beads are made by ionic cross-linking of the biopolymer alginate using copper (Cu2+) cations. The killer capsules harvest glucose from their surroundings, which is then enzymatically converted by GOx into gluconate ions. These ions are known for their ability to chelate Cu2+ cations. Thus, when a killer capsule is next to a target alginate bead, the gluconate ions diffuse...

External triggers such as pH or temperature can induce hydrogels to swell or shrink rapidly. Recently, these triggers have also been used to alter the three-dimensional (3-D) shapes of gels: for example, a flat gel sheet can be induced to fold into a tube. Self-folding gels are reminiscent of natural structures such as the Venus flytrap, which folds its leaves to entrap its prey. They are also of interest for applications in sensing or microrobotics. However, to advance the utility of self-folding gels, the range of triggers needs to be expanded beyond the conventional ones. Toward this end, we have designed a class of gels that change shape in response to very low concentrations of specific biomolecules. The gels are hybrids of three different constituents: (A) polyethylene glycol diacrylate (PEGDA); (B) gelatin methacrylate-co-polyethylene glycol dimethacrylate (GelMA-co-PEGDMA); and (C) N-isopropylacrylamide (NIPA). The thin-film hybrid is constructed as a bilayer or sandwich of two layers, with an A/B layer (alternating strips of A and B) sandwiched above a layer of gel C. Initially, when this hybrid gel is placed in water, the C layer is much more swollen than the A/B layer. Despite the swelling mismatch, the sheet remains flat because the A/B layer is very stiff. When collagenase enzyme is added to the water, it cleaves the gelatin chains in B, thus reducing the stiffness of the A/B layer. As a result, the swollen C layer is able to fold over the A/B layer, causing the sheet to transform into a specific shape. The typical transition is from flat sheet to closed hollow tube, and the time scale for this transition decreases with increasing enzyme concentration. Shape transitions are induced by enzyme levels as low as 0.75 U/mL. Interestingly, a shape transition is also induced by adding the lysate of murine fibroblast cells, which contains enzymes from the matrix metalloproteinase (MMP) family at levels around 0.1 U/mL (MMPs are similar to collagenase in their ability to cleave gelatin). We further show that transitions from flat sheets to other shapes such as helices and pancakes can be engineered by altering the design pattern of the gel. Additionally, we have made a rudimentary analog of the Venus flytrap, with two flat gels ("leaves") flanking a central folding gel ("hinge"). When enzyme is added, the hinge bends and brings the leaves together, trapping objects in the middle.

When administered intravenously, active targeting of drug nanocarriers (NCs) improves biodistribution and endocytosis. Targeting may also improve oral delivery of NCs to treat gastrointestinal (GI) pathologies or for systemic absoption. However, GI instability of targeting moieties compromises this strategy. We explored whether encapsulation of antibody-coated NCs in microcapsules would protect against gastric degradation, providing NCs release and targeting in intestinal conditions. We used nanoparticles coated with antibodies against intercellular adhesion molecule-1 (anti-ICAM) or non-specific IgG. NCs (~160-nm) were encapsulated in ~180-μm microcapsules with an alginate core, in the absence or presence of a chitosan shell. We found >95% NC encapsulation within microcapsules and

Effectiveness of oil spill dispersants containing lecithin/Tween 80 (L/T) blends in ethanol was measured as a function of L:T ratio, surfactant:solvent ratio, solvent composition, and dispersant:oil ratio (DOR) using baffled flask dispersion effectiveness tests. Optimal L:T ratios are between 60:40 and 80:20 (w/w); at higher L:T ratios, effectiveness is limited by high interfacial tension, while at lower L:T ratios, insufficient lecithin is present to form a well-packed monolayer at an oil-water interface. These optimal L:T ratios retain high effectiveness at low DOR: 80:20 (w/w) L:T dispersant is 89% effective at 1:25 DOR (v/v) and 77% effective at 1:100 DOR (v/v). Increasing surfactant:solvent ratio increases dispersant effectiveness even when DOR is proportionally reduced to keep total surfactant concentration dosed into the oil constant. Replacing some of the ethanol with octane or octanol also increases dispersant effectiveness, suggesting that ethanol's hydrophilicity lowers dispersant-oil miscibility, and that more hydrophobic solvents would increase effectiveness.

Background A novel injectable expanding foam based on hydrophobically modified chitosan (HM-CS) was developed to improve hemostasis during surgeries. HM-CS is an amphiphilic derivative of the natural biopolymer chitosan (CS); HM-CS has been shown to improve the natural hemostatic characteristics of CS, but its internal safety has not been systematically evaluated. The goal of this study was to compare the long-term in vivo safety of HM-CS relative to a commonly used fibrin sealant (FS), TISSEEL (Baxter). Methods Sixty-four Sprague–Dawley rats (275-325 g obtained from Charles River Laboratories) were randomly assigned to control (n = 16) or experimental (n = 48) groups. Samples of the test materials (HM-CS [n = 16], CS [n = 16], and FS [n = 16]) applied to a nonlethal liver excision (0.4 ± 0.3 g of the medial lobe) in rats were left inside the abdomen to degrade. Animals were observed daily for signs of morbidity and mortality. Surviving animals were sacrificed at 1 and 6 wk; the explanted injury sites were microscopically assessed. Results All animals (64/64) survived both the 1- and 6-wk time points without signs of morbidity. Histological examination showed a comparable pattern of degradation for the various test materials. FS remnants and significant adhesions to neighboring tissues were observed at 6 wk. Residual CS and HM-CS were observed at the 6 wk with fatty deposits at the site of injury. Minimal adhesions were observed for CS and HM-CS. Conclusions The internal safety observed in the HM-CS test group after abdominal implantation indicates that injectable HM-CS expanding foam may be an appropriate internal use hemostatic candidate.

We describe the creation of hollow tubular hydrogels in which different zones along the length of the tube are composed of different gels. Our method to create these gels is adapted from a technique developed previously in our lab for creating solid hybrid hydrogels. The zones of our tubular gel are covalently bonded at the interfaces; as a result, these interfaces are highly robust. Consequently, the tube can be picked up, manipulated and stretched without suffering any damage. The hollow nature of these gels allows them to respond 2⁻30-fold faster to external stimuli compared to a solid gel of identical composition. We study the case where one zone of the hybrid tube is responsive to pH (due to the incorporation of an ionic monomer) while the other zones are not. Initially, the entire tube has the same diameter, but when pH is changed, the diameter of the pH-responsive zone alone increases (i.e., this zone bulges outward) while the other zones maintain their original diameter. The net result is a drastic change in the shape of the gel, and this can be reversed by reverting the pH to its original value. Similar localized changes in gel shape are shown for two other stimuli: temperature and solvent composition. Our study points the way for researchers to design three-dimensional soft objects that can reversibly change their shape in response to stimuli.

Molecular organogelators convert oils into gels by forming self-assembled fibrous networks. Here, we demonstrate that such gelation can be activated by contacting the oil with an immiscible solvent (water). Our gelator is dibenzylidene sorbitol (DBS), which forms a low-viscosity sol when added to toluene containing a small amount of dimethyl sulfoxide (DMSO). Upon contact with water, DMSO partitions into the water, activating gelation of DBS in the toluene. The gel grows from the oil/water interface and slowly envelops the oil phase. We have exploited this effect for the self-repair of oil leaks from underwater tubes. When a DBS/toluene/DMSO solution flows through the tube, it forms a gel selectively at the leak point, thereby plugging the leak and restoring flow. Our approach is reminiscent of wound-sealing via blood-clotting: there also, inactive gelators in blood are activated at the wound site into a fibrous network, thereby plugging the wound and restoring blood flow.

Trauma represents a significant public health burden, and hemorrhage alone is responsible for 40% of deaths within the first 24 h after injury. Noncompressible hemorrhage accounts for the majority of hemorrhage-related deaths. Thus, materials which can arrest bleeding rapidly are necessary for improved clinical outcomes. This preliminary study evaluated several self-expanding hydrophobically modified chitosan (HM-CS) foams to determine their efficacy on a noncompressible severe liver injury under resuscitation.Six HM-CS foam formulations (HM-CS1, HM-CS2, HM-CS3, HM-CS4, HM-CS5, and HM-CS6) of different graft types and densities were synthesized, characterized, and packaged into spray canisters using dimethyl ether as the propellant. Expansion profiles of the foams were evaluated in bench testing. Foams were then evaluated in vitro, interaction with blood cells was determined via microscopy, and cytotoxicity was assessed via live-dead cell assay on MCF7 breast cancer cells. For in vivo evaluation, rats underwent a 14 ± 3% hepatectomy. The animals were treated with either: (1) an HM-CS foam formulation, (2) CS foam, and (3) no treatment (NT). All animals were resuscitated with lactated Ringer solution. Survival, total blood loss, mean arterial pressures (MAP), and resuscitation volume were recorded for 60 min.Microscopy showed blood cells immobilizing into colonies within tight groups of adjacent foam bubbles. HM-CS foam did not display any toxic effects in vitro on MCF7 cells over a 72 h period studied. Application of HM-CS foam after hepatectomy decreased total blood loss (29.3 ± 7.8 mL/kg in HM-CS5 group versus 90.9 ± 20.3 mL/kg in the control group; P0.001) and improved survival from 0% in controls to 100% in the HM-CS5 group (P0.001).In this model of severe liver injury, spraying HM-CS foams directly on the injured liver surface decreased blood loss and increased survival. HM-CS formulations with the highest levels of hydrophobic modification (HM-CS4 and HM-CS5) resulted in the lowest total blood loss and highest survival rates. This pilot study suggests HM-CS foam may be useful as a hemostatic adjunct or solitary hemostatic intervention.

A highly porous 2D nanomaterial, holey graphene oxide (hGO), is synthesized directly from holey graphene powder and employed to create an aqueous 3D printable ink without the use of additives or binders. Stable dispersions of hydrophilic hGO sheets in water (≈100 mg mL-1 ) can be readily achieved. The shear-thinning behavior of the aqueous hGO ink enables extrusion-based printing of fine filaments into complex 3D architectures, such as stacked mesh structures, on arbitrary substrates. The freestanding 3D printed hGO meshes exhibit trimodal porosity: nanoscale (4-25 nm through-holes on hGO sheets), microscale (tens of micrometer-sized pores introduced by lyophilization), and macroscale (

The self-assembly of biological surfactants in water is an important topic for study because of its relevance to physiological processes. Two common types of biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both present in bile and involved in digestion. Previous studies on lecithin-bile salt mixtures have reported the formation of short, rodlike micelles. Here, we show that lecithin-bile salt micelles can be further induced to grow into long, flexible wormlike structures. The formation of long worms and their resultant entanglement into transient networks is reflected in the rheology: the fluids become viscoelastic and exhibit Maxwellian behavior, and their zero-shear viscosity can be up to a 1000-fold higher than that of water. The presence of worms is further confirmed by data from small-angle neutron and X-ray scattering and from cryo-transmission electron microscopy (cryo-TEM). We find that micellar growth peaks at a specific molar ratio (near equimolar) of bile salt:lecithin, which suggests a strong binding interaction between the two species. In addition, micellar growth also requires a sufficient concentration of background electrolyte such as NaCl or sodium citrate that serves to screen the electrostatic repulsion of the amphiphiles and to "salt out" the amphiphiles. We postulate a mechanism based on changes in the molecular geometry caused by bile salts and electrolytes to explain the micellar growth.

Physics and chemistry underpinned the remarkable advances in materials science that occurred during the 20th century, while biology is poised to provide the scientific underpinning for materials science advances of the 21st century. Biofabrication is the emerging approach to broadly apply biology's materials and mechanisms to create structure and function. Here, we describe one such biofabrication methodology, the use of tyrosinase to graft phenolics to the aminopolysaccharide chitosan. Phenolics are a broad class of abundant natural products and we provide results from a single phenolic reactant, caffeic acid, to illustrate the potential for enzymatically imparting functional properties to chitosan. We show that tyrosinase oxidation mediates the grafting of caffeic acid to chitosan and possibly even results in the covalent crosslinking of chitosan. When this enzymatic reaction is performed in a chitosan solution (pH

Polymer hydrogels synthesized by chemical cross-linking of acrylate or acrylamide monomers can absorb more than 100 times their weight in water. However, such gels are usually fragile and rupture when stretched to moderate strains (∼50%). Many strategies have been developed to create tougher gels, including double-networking, incorporation of nanoparticles as cross-linkers, etc., but these strategies typically retard the water absorbency of the gel. Here, we present a new approach that gives rise to superabsorbent hydrogels having superior mechanical properties. The key to our approach is the self-cross-linking ability of N,N-dimethylacrylamide (DMAA). That is, we conduct a free-radical polymerization of DMAA (along with an ionic comonomer such as sodium acrylate) but without any multifunctional monomers. A hydrogel still forms due to interchain covalent bonds between the growing linear polymer chains. Gels formed by this route can be stretched up to 1350% strain in the unswollen state. The same gels are ...

The self-assembly of a hydrophobically modified biopolymer (chitosan) is described with particular reference to gelation of these systems. The hydrophobic modification consists of the attachment of long chain alkyl groups inserted randomly along the polysaccharide backbone. The attachment of these alkyl groups to hydrophobic surfaces or the insertion into nonpolar liquids provides a ubiquitous and versatile way to create hierarchical structures, particularly the formation of self-assembled gels. Such self-assembly can be used in a variety of new technologies relating to chromatography, lubrication and the environmental remediation of oil spills through gelation of surface layers.

We examine the gelation of alginate undergoing ionic crosslinking upon ultraviolet (UV) irradiation using in situ dynamic rheology. Hydrogels are formed by combining alginate with calcium carbonate (CaCO3) particles and a photoacid generator (PAG). The PAG is photolyzed upon UV irradiation, resulting in the release of free calcium ions for ionic crosslinking. The viscous and elastic moduli during gelation are monitored as a function of the UV irradiation intensity, exposure time, alginate concentration, and the ratio between alginate and calcium carbonate. Gel time decreases as irradiation intensity increases because a larger concentration of PAG is photolyzed. Interestingly, dark curing, the continuing growth of microstructure in the absence of UV light, is observed. In some instances, the sample transitions from a solution to a gel during the dark curing phase. Additionally, when exposed to constant UV irradiation after the dark curing phase, samples reach the same plateau modulus as samples exposed to constant UV without dark curing, implying that dark curing does not affect the gelation mechanism. We believe the presence of dark curing is the result of the acidic environment persisting within the sample, allowing CaCO3 to dissociate, thereby releasing free Ca(2+) ions capable of binding with the available appropriate ionic blocks of the polymer chains. The growth of microstructure is then detected if the activation barrier has been crossed to release sufficient calcium ions. In this regard, we calculate a value of 30 J that represents the activation energy required to initiate gelation.

Liposomal coatings are formed on films of a biopolymer, hydrophobically modified chitosan (hm-chitosan), containing dodecyl groups as hydrophobes along the polymer backbone. The alkyl groups insert themselves into the liposome bilayer through hydrophobic interactions and thus tether liposomes, leading to a densely packed liposome layer on the film surface. Such liposomal surfaces exhibit effective lubrication properties due to their high degree of hydration, and reduce the coefficient of friction to the biologically-relevant range. The compliancy and robustness of these tethered liposomes allow retention on the film surface upon repeated applications of shear. Such liposome coated films have potential applications in biolubrication.

Diverse structures in nature, such as the spinal disc and the onion have many concentric layers, and are created starting from the core and proceeding outwards. Here, we demonstrate an inside-out technique for creating multilayered polymer capsules. First, an initiator-loaded gel core is placed in a solution of monomer 1. The initiator diffuses outward and induces polymerization, leading to a shell of polymer 1. Thereafter, the core-shell structure is loaded with fresh initiator and placed in monomer 2, which causes a concentric shell of polymer 2 to form around the first shell. This process can be repeated to form multiple layers, each of a distinct polymer, and of controlled layer thickness. We show that these multilayered capsules can exhibit remarkable mechanical resilience as well as stimuli-responsive properties. The release of solutes from these capsules can be tailored to follow specific profiles depending on the chemistry and order of adjacent layers., Multiple concentric layers are present in a variety of structures present in nature, including the onion. Here, the authors show an inside-out strategy to synthesize multilayered polymer capsules, with different layers having specific composition and thereby specific responses to stimuli such as pH and temperature.

We describe a new class of hierarchical containers that are formed via single-step assembly and, at a later time, self-destruct because of their packaged contents. These containers are spherical capsules formed by electrostatic complexation of the anionic biopolymer, gellan gum, with the cationic biopolymer, chitosan. The capsules are termed "motherships" and are engineered to carry a cargo of much smaller containers (e.g., nanoscale liposomes ("babyships")), within their lumen. Additionally, we package an enzyme, chitosanase, in the capsule that is capable of degrading polymeric chitosan into short oligomers. Thereby, we create motherships that self-destruct, liberating their cargo of babyships into the external solution. The time scale for self-destruction can be engineered based on the internal concentration of enzyme. The motherships are stable when stored in a freeze-dried form and can be readily dispersed into water or buffer solutions at a later time, whereupon their "internal clock" for self-destruction is initiated. The above concept could be useful for the triggered release of a variety of payloads including drugs, biological therapeutics, cosmetics, and flavor ingredients.

The self-assembly behavior of a series of glucono-appended 1-pyrenesulfonyl derivatives containing α,ω-diaminoalkane spacers (Pn, where n, the number of methylene units separating the amino groups, is 2, 3, 4, 6, 7, and 8) in v:v tetrahydrofuran (THF):water mixtures is examined at room temperature. The Pn at 2 w/v % concentrations do not dissolve in either THF or water at room temperature. However, the Pn can be dissolved in some THF:water mixtures, and they form gels spontaneously in other compositions without dissolving completely. The self-assembly of the Pn in the liquid mixtures has been investigated using a variety of techniques. The particle sizes of the Pn in their solutions/sols, critical gelation concentrations, microstructures, thermal and mechanical stabilities of the gels, and molecular packing modes of Pn molecules in their gel networks are found to be very dependent on the composition of the liquid mixtures. Correlations between the self-assembly behavior of the Pn and the polarity of the liquid mixtures, as probed by E(T)(30) and Hansen solubility parameters, yield both qualitative and quantitative insights into why self-assembly of the Pn can or cannot be achieved in different liquid compositions. As revealed by UV-vis and fluorescence spectroscopy studies, π-π stacking of the pyrenyl groups occurs as part of the aggregation process. Correlations between the rheological properties of the gels and the Hansen solubility parameters of the Pn and the solvent mixtures indicate that hydrogen-bonding interactions are a major contributor to the mechanical stability. Overall, the results of this study offer a new strategy to investigate the balance between dissolution and aggregation of molecular gelators. To the best of our knowledge, this is the first example of the spontaneous formation of molecular gels without heating by placing gelators in mixtures of liquids in which they are insoluble in the neat components.

The stability of crude oil droplets formed by adding chemical dispersants can be considerably enhanced by the use of the biopolymer, hydrophobically modified chitosan. Turbidimetric analyses show that emulsions of crude oil in saline water prepared using a combination of the biopolymer and the well-studied chemical dispersant (Corexit 9500A) remain stable for extended periods in comparison to emulsions stabilized by the dispersant alone. We hypothesize that the hydrophobic residues from the polymer preferentially anchor in the oil droplets, thereby forming a layer of the polymer around the droplets. The enhanced stability of the droplets is due to the polymer layer providing an increase in electrostatic and steric repulsions and thereby a large barrier to droplet coalescence. Our results show that the addition of hydrophobically modified chitosan following the application of chemical dispersant to an oil spill can potentially reduce the use of chemical dispersants. Increasing the molecular weight of the biopolymer changes the rheological properties of the oil-in-water emulsion to that of a weak gel. The ability of the biopolymer to tether the oil droplets in a gel-like matrix has potential applications in the immobilization of surface oil spills for enhanced removal.

Lithium-ion batteries have emerged as the preferred type of rechargeable batteries, but there is a need to improve the performance of the electrolytes therein. Specifically, the challenge is to obtain electrolytes with the mechanical rigidity of solids but with liquid-like conductivities. In this study, we report a class of nanostructured gels that are able to offer this unique combination of properties. The gels are prepared by utilizing the synergistic interactions between a molecular gelator, 1,3:2,4-di-O-methyl-benzylidene-d-sorbitol (MDBS), and a nanoscale particulate material, fumed silica (FS). When MDBS and FS are combined in a liquid consisting of propylene carbonate with dissolved lithium perchlorate salt, the liquid electrolyte is converted into a free-standing gel due to the formation of a strong MDBS-FS network. The gels exhibit elastic shear moduli around 1000 kPa and yield stresses around 11 kPa-both values considerably exceed those obtainable by MDBS or FS alone in the same liquid. At the same time, the gel also exhibits electrochemical properties comparable to the parent liquid, including a high ionic conductivity (~5 × 10(-3) S/cm at room temperature) and a wide electrochemical stability window (up to 4.5 V).

A series of glucono-appended 1-pyrenesulfonyl derivatives containing α,ω-diaminoalkane spacers (Pn, where n, the number of methylene units separating the amino groups, is 2, 3, 4, 6, 7, and 8) have been prepared. Careful analyses of correlations between the structures of these molecules and their gels have provided important insights into the factors responsible for one-dimensional aggregation of small molecules containing both lipophilic and hydrophilic parts. The gelation behavior has been examined in 30 liquids of diverse structure and polarity, and the properties of their gels and the gelation mechanisms have been investigated using a variety of techniques. Possible reasons are discussed regarding why the Pn are better gelators than the corresponding naphthyl analogues (Nn) which had been investigated previously. P2 and P3 are ambidextrous gelators (i.e., they gelate both water and some organic liquids), and P4-P8 gelate some organic liquids which are protic and aprotic, but not water. In at least one of the liquids examined, P3, P4, P6, P7, and P8 form gels at less than 1 w/v % concentrations, and some of the gels in 1-decanol are thixotropic. Analyses of the gelation abilities using Hansen solubility parameters yield both qualitative and quantitative insights into the role of liquid-gelator interactions. For example, the critical gelation concentrations increase generally with increasing polar and hydrogen bonding interactions between the gelators and their liquid components. As revealed by FT-IR, (1)H NMR, UV-vis, and fluorescence spectra, hydrogen-bonding between glucono units and π-π stacking between pyrenyl groups are important in the formation and maintenance of the gel networks. The results from this study, especially those relating the aggregation modes and liquid properties, offer insights for the design of new surfactant-containing low-molecular-mass gelators with predefined gelating abilities.

Self-assembly of lipids in water is well-known to result in nanostructures such as vesicles in dilute solution. In contrast, self-assembly in nonpolar organic solvents (oils) is much less established and there are hardly any known routes to forming structures such as reverse vesicles. Here, we build such structures based on our surprising recent discovery that salts can influence self-assembly of lipids in oil. We induce the self-assembly of nanoscale multilamellar vesicles (“onions”) in cyclohexane and toluene by combining the saturated phospholipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), with salts of di- or trivalent cations like calcium (Ca2+) or gadolinium (Gd3+) in the absence of water. DMPC–Gd3+ onions can be seen by a transmission electron microscope (TEM) without additional staining. They have sizes between ∼100 and 400 nm and have 6–18 concentric bilayer shells (lamellae) that are uniformly spaced. The presence of lamellae is further confirmed by small-angle X-ray scattering (SAXS), from which we find the inter-lamellar spacing to be 6.0 nm. The formation of reverse onions is driven by the binding of these multivalent cations with the lipid headgroups, which in turn brings adjacent lipids close and causes a tighter packing of the lipid tails. Evidence for such binding is provided by the cation-induced lowering of the lipid melting temperature.

A photoresponsive micellar solution is developed as a promising working fluid for district heating/cooling systems (DHCs). It can be reversibly switched between a drag reduction (DR) mode and an efficient heat transfer (EHT) mode by light irradiation. The DR mode is advantageous during fluid transport, and the EHT mode is favored when the fluid passes through heat exchangers. This smart fluid is an aqueous solution of cationic surfactant oleyl bis(2-hydroxyethyl)methyl ammonium chloride (OHAC, 3.4 mM) and the sodium salt of 4-phenylazo benzoic acid (ACA, 2 mM). Initially, ACA is in a trans configuration and the OHAC/ACA solution is viscoelastic and exhibits DR (of up to 80% relative to pure water). At the same time, this solution is not effective for heat transfer. Upon UV irradiation, trans-ACA is converted to cis-ACA, and in turn, the solution is converted to its EHT mode (i.e., it loses its viscoelasticity and DR) but it now has a heat-transfer capability comparable to that of water. Subsequent irradiation with visible light reverts the fluid to its viscoelastic DR mode. The above property changes are connected to photoinduced changes in the nanostructure of the fluid. In the DR mode, the OHAC/trans-ACA molecules assemble into long threadlike micelles that impart viscoelasticity and DR capability to the fluid. Conversely, in the EHT mode the mixture of OHAC and cis-ACA forms much shorter cylindrical micelles that contribute to negligible viscoelasticity and effective heat transfer. These nanostructural changes are confirmed by cryo-transmission electron microscopy (cryo-TEM), and the photoisomerization of trans-ACA and cis-ACA is verified by (1)H NMR.

This paper reports a simple, rapid, and sugar-selective method to induce gelation from glucose-containing samples. This method employs glucose oxidase (GOx) to selectively "recognize" and oxidize glucose to generate gluconic acid, which acts to solubilize calcium carbonate and release calcium ions. The release of calcium ions triggers gelation of the calcium-responsive polysaccharide alginate to form a calcium-alginate hydrogel. Rheological measurements confirm that gel formation is triggered by glucose but not fructose or sucrose (consistent with GOx's selectivity). Vial inversion tests demonstrate that gel formation can be readily observed without the need for instrumentation. Proof-of-concept studies demonstrate that this gel-forming method can detect glucose in food/beverage products sweetened with glucose or high-fructose corn syrups. These results indicate that the enzyme-induced gelation of alginate may provide a simple means to test for sweeteners using components that are safe for use on-site or in the home.

We describe a new approach to creating hybrid polymer hydrogels that comprise two different gel types (gel 1 and gel 2) juxtaposed in predetermined zones or patterns and with the unique properties of each gel being retained. The key to our approach is to ensure that the viscosities of the pregel mixtures are high when they are brought into contact and subsequently polymerized; this limits the diffusion at gel/gel interfaces. The final gel appears as a single, homogeneous, transparent material with smooth, robust interfaces between the dissimilar zones. However, its hybrid nature is revealed by specific tests. In one example, we use the same monomer, N,N-dimethylacrylamide, for gels 1 and 2, but gel 1 is cross-linked by a chemical cross-linker while gel 2 is cross-linked by laponite nanoparticles. In this case, when the hybrid gel is immersed in a mixed solution of cationic and anionic dyes, gel 2 selectively absorbs the cationic dye due to the strong affinity of the nanoparticles in it for cationic specie...

An easy access to a library of simple organic salts derived from tert-butoxycarbonyl (Boc)-protected L-amino acids and two secondary amines (dicyclohexyl- and dibenzyl amine) are synthesized following a supramolecular synthon rationale to generate a new series of low molecular weight gelators (LMWGs). Out of the 12 salts that we prepared, the nitrobenzene gel of dicyclohexylammonium Boc-glycinate (GLY.1) displayed remarkable load-bearing, moldable and self-healing properties. These remarkable properties displayed by GLY.1 and the inability to display such properties by its dibenzylammonium counterpart (GLY.2) were explained using microscopic and rheological data. Single crystal structures of eight salts displayed the presence of a 1D hydrogen-bonded network (HBN) that is believed to be important in gelation. Powder X-ray diffraction in combination with the single crystal X-ray structure of GLY.1 clearly established the presence of a 1D hydrogen-bonded network in the xerogel of the nitrobenzene gel of GLY.1. The fact that such remarkable properties arising from an easily accessible (salt formation) small molecule are due to supramolecular (non-covalent) interactions is quite intriguing and such easily synthesizable materials may be useful in stress-bearing and other applications.

Current gels used in blood separation tubes create an imperfect barrier between the blood components because of their physical and thixotropic nature. As a result, blood components tend to leak into the gel layer or vice versa during transport and storage. To overcome these problems, we demonstrate the use of a UV-curable thixotropic gel composed of a sorbitol-based gelator in a diacrylate oligomer. Initially, the sample is a physical gel composed of weak, non-covalent bonds, and its thixotropic nature allows it to flow under centrifugation and form a barrier between the density-stratified layers of blood. Immediately afterward, the gel is chemically crosslinked by short exposure to UV light for 10–30 s. This results in a rigid, impenetrable barrier that is freeze-thaw stable. The gel is compatible with blood, allowing blood samples to be stored in the tube and analyzed over long times. We believe the present method is a significant advance in the practice of blood analysis for medical purposes.

We describe the creation of monodisperse microbeads of polydimethylsiloxane (PDMS) via a microfluidic approach. Using a flow-focusing configuration, a PDMS precursor solution is dispersed into microdroplets within an aqueous continuous phase. These droplets are collected and thermally cured off-chip into solid microbeads. Our microfluidic technique allows for direct integration of payloads into the PDMS microbeads. Specifically, we integrate an oxygen-sensitive porphyrin dye into the beads and show that the resulting structures can function as non-invasive and real-time oxygen microsensors utilizing a simple optical readout at the single-particle level.

Alginate is a biocompatible polysaccharide that is commonly used in the pharmaceutical, biomedical, cosmetic, and food industries. Though solid dressings composed of alginate can absorb water and promote wound healing, they are not effective hemostatic materials, particularly against massive hemorrhage. The purpose of this study is to attempt to increase the hemostatic capabilities of alginate by means of hydrophobic modification. Previous studies have illustrated that modifying a different polysaccharide, chitosan, in this way enhances its hemostatic efficacy as well as its adhesion to tissue. Here, it was hypothesized that modifying alginate with hydrophobic groups would demonstrate analogous effects.Fifteen Yorkshire swine were randomized to receive hydrophobically-modified (hm) alginate lyophilized sponges (n=5), unmodified alginate lyophilized sponges (n=5), or standard Kerlix™ gauze dressing (n=5) for hemostatic control. Following a splenectomy, arterial puncture (6mm punch) of the femoral artery was made. Wounds were allowed to freely bleed for 30s, at which time dressings were applied and compressed for 3min in a randomized fashion. Fluid resuscitation was given to preserve the baseline mean arterial pressure. Wounds were monitored for 180min after arterial puncture, and surviving animals were euthanized.Blood loss for the hm-alginate group was significantly less than the two control groups of (1) alginate and (2) Kerlix™ gauze (p=0.0001). Furthermore, 80% of hm-alginate sponges were able to sustain hemostasis for the full 180min, whereas 0% of dressings from the control groups were able to achieve initial hemostasis.Hm-alginate demonstrates a greatly superior efficacy, relative to unmodified alginate and Kerlix™ gauze dressings, in achieving hemostasis from a lethal femoral artery puncture in swine. This is a similar result as has been previously described when performing hydrophobic modification to chitosan. The current study further suggests that hydrophobic modification of a hydrophilic biopolymer backbone can significantly increase the hemostatic capabilities relative to the native biopolymer.

Biopolymers such as alginate and pectin are well known for their ability to undergo gelation upon addition of multivalent cations such as calcium (Ca(2+)). Here, we report a simple way to activate such ionic gelation by UV irradiation. Our approach involves combining an insoluble salt of the cation (e.g., calcium carbonate, CaCO(3)) with an aqueous solution of the polymer (e.g., alginate) along with a third component, a photoacid generator (PAG). Upon UV irradiation, the PAG dissociates to release H(+) ions, which react with the CaCO(3) to generate free Ca(2+). In turn, the Ca(2+) ions cross-link the alginate chains into a physical network, thereby resulting in a hydrogel. Dynamic rheological experiments confirm the elastic character of the alginate gel, and the gel modulus is shown to be tunable via the irradiation time as well as the PAG and alginate concentrations. The above approach is easily extended to other biopolymers such as pectin. Using this approach, a photoresponse can be imparted to conventional biopolymers without the need for any chemical modification of the molecules. Photoresponsive alginate gels may be useful in creating biomaterials or tissue mimics. As a step toward potential applications, we demonstrate the ability to photopattern a thin film of alginate gel onto a glass substrate under mild conditions.

Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic plug, i.e., a self-assembled network of the protein, fibrin that locally transforms liquid blood into a gelled clot. Here, we report an amphiphilic biopolymer that exhibits a similar ability to rapidly gel blood; moreover, the self-assembly underlying the gelation readily allows for reversibility back into the liquid state via introduction of a sugar-based supramolecule. The biopolymer is a hydrophobically modified (hm) derivative of the polysaccharide, chitosan. When hm-chitosan is contacted with heparinized human blood, it rapidly transforms the liquid into an elastic gel. In contrast, the native chitosan (without hydrophobes) does not gel blood. Gelation occurs because the hydrophobes on hm-chitosan insert into the membranes of blood cells and thereby connect the cells into a sample-spanning network. Gelation is reversed by the addition of α-cyclodextrin, a supramolecule having an inner hydrophobic pocket: polymer hydrophobes unbind from blood cells and embed within the cyclodextrins, thereby disrupting the cell network. We believe that hm-chitosan has the potential to serve as an effective, yet low-cost hemostatic dressing for use by trauma centers and the military. Preliminary tests with small and large animal injury models show its increased efficacy at achieving hemostasis - e.g., a 90% reduction in bleeding time over controls for femoral vein transections in a rat model.

We describe a simple way to create patterns of “soft” biomolecular nanostructures such as vesicles on “hard” surfaces such as gold. The key to our approach is the use of an amphiphilic biopolymer as an “interconnect” or tether. The polymer is hydrophobically modified chitosan (hm-chitosan), which is obtained by covalently attaching alkyl tails to the backbone of chitosan. We electrodeposit films of hm-chitosan onto microscale gold cathodes formed by lithography on a silicon wafer. Subsequently, the hm-chitosan films are used to spontaneously capture vesicles from solution; this is demonstrated both for surfactant as well as lipid vesicles (liposomes). Vesicles remain strongly bound to the hm-chitosan to a much greater extent than to native chitosan. This suggests that the mechanism for vesicle capture involves non-covalent binding of hydrophobes from hm-chitosan chains to the hydrophobic portions of vesicle bilayers. Importantly, the vesicles captured by hm-chitosan films are intact—this is shown both by direct visualization of captured vesicles (via optical and cryo-transmission electron microscopy) as well as through the capture and subsequent disruption of dye-filled vesicles. Various microscale patterns of immobilized vesicles are created and the vesicles are demonstrated to be capable of sensing a reporter molecule from the external solution.

Easy access to a class of chiral gelators has been achieved by exploiting primary ammonium mono- carboxylate (PAM), a supramolecular synthon. A combinatorial library com- prising of 16 salts, derived from 5 l- amino acid methyl esters and 4 cinnam- ic acid derivatives, has been prepared and scanned for gelation. Remarkably, 14 out of 16 salts prepared (87.5 % of the salts) show moderate to good gela- tion abilities with various solvents, in- cluding commercial fuels, such as petrol. Anti-solvent induced instant ge- lation at room temperature has been achieved in all the gelator salts, indicat- ing that the gelation process is indeed an aborted crystallization phenomenon. Rheology, optical and scanning elec- tron microscopy, small angle neutron scattering, and X-ray powder diffrac- tion have been used to characterize the gels. A structure-property correlation has been attempted, based on these data, in addition to the single-crystal structures of 5 gelator salts. Analysis of the FT-IR and 1 H NMR spectroscopy data reveals that some of these salts can be used as supramolecular contain- ers for the slow release of certain pest sex pheromones. The present study clearly demonstrates the merit of crys- tal engineering and the supramolecular synthon approach in designing new ma- terials with multiple properties.

We describe a new way to impart pH-responsive properties to gels of biopolymers such as gelatin. This approach involves the embedding of pH-sensitive nanosized vesicles within the gel. The vesicles employed here are those of sodium oleate (NaOA), a fatty-acid-based amphiphile with a single C18 tail. In aqueous solution, NaOA undergoes a transition from vesicles at a pH approximately 8 to micelles at a pH higher than approximately 10. Here, we combine NaOA and gelatin at pH 8.3 to create a vesicle-loaded gel and then bring the gel in contact with a pH 10 buffer solution. As the buffer diffuses into the gel, the vesicles within the gel get transformed into micelles. Accordingly, a vesicle-micelle front moves through the gel, and this can be visually identified by the difference in turbidity between the two regions. Vesicle disruption can also be done in a spatially selective manner to create micelle-rich domains within a vesicle-loaded gel. A possible application of the above approach is in the area of pH-dependent controlled release. A vesicle-to-micelle transition releases hydrophilic solutes encapsulated within the vesicles into the bulk gel, and in turn these solutes can rapidly diffuse out of the gel into the external bath. Experiments with calcein dye confirm this concept and show that we can indeed use the pH in the bath to tune the release rate of solutes from vesicle-loaded gels.