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Background: In elastic and resistance arteries, an elastin-rich membrane, the Internal Elastic Lamina (IEL), separates the tunica intima from the underlying tunica media. The IEL often appears wrinkled or corrugated in histological images. These corrugations are sometimes ascribed to vessel contraction ex vivo, and to fixation artifacts, and therefore regarded as not physiologically relevant. We examine whether the IEL remains corrugated even under physiological conditions., Methods: The diameters of carotid arteries of anesthetized pigs were measured by ultrasound. The arteries were then excised, inflated within a conical sleeve, fixed, and imaged by confocal microscopy. The conical sleeve allows fixing each artery across a wide range of diameters, which bracket its ultrasound diameter. Thus the study was designed to quantify how corrugations change with diameter for a single artery, and test whether corrugations exist when the fixed artery matches the ultrasound diameter., Results: At diameters below the ultrasound diameter (i.e. when the artery was constricted as compared to ultrasound conditions), the IEL corrugations were found to decrease significantly with increasing diameter, but not fully flatten at the ultrasound diameter. The contour length of the IEL was found to be roughly 10% larger than the circumference of the artery measured by ultrasound. Since ultrasound was conducted with the animal under general anesthesia which induces vasodilation, the physiological diameter is likely to be smaller than the ultrasound diameter, and hence the arteries are likely to have a higher level of corrugation under physiological conditions. For arterial cross sections constricted below the ultrasound diameter, the IEL contour length decreased roughly with the square root of the diameter., Conclusion: The primary conclusions of this study are: a) the IEL is corrugated when the artery is constricted and flattens as the artery diameter increases; b) the IEL is corrugated under physiological conditions and has a contour length at least 10% more than the physiological arterial diameter; and c) the IEL despite being relatively stiffer than the surrounding arterial layers, does not behave like an inextensible membrane., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

When a soft tube is inflated, it may sometimes show a bulge instability wherein a portion of the tube inflates much more than the rest. The bulge instability is well-understood for hyperelastic materials. We examine inflation of polyurethane tubes whose material behavior is not strictly hyperelastic. Upon inflating at constant rate, the tubes deform into a variety of shapes including irregular axisymmetric shapes with multiple localized bulges, a single axially-propagating bulge, or homogeneous cylindrical shapes. In all cases regardless of the inflation mode, the pressure first rises to a maximum, and then gradually reduces towards a plateau. We document numerous differences as compared to hyperelastic tubes. Most notably a pressure maximum can appear even without bulging, whereas for hyperelastic tubes, a pressure maximum is necessarily accompanied by bulging. Further, the decrease in pressure beyond the maximum occurs gradually over timescales as long as an hour, whereas bulging of hyperelastic tubes induces an instantaneous drop in pressure. We also observe permanent deformation upon deflation, a decrease in the pressure maximum during a subsequent second inflation, and more severe bulge localization at low inflation rates. Existing theory of hyperelastic tube inflation cannot capture the observed behaviors, even qualitatively. Finite element simulations suggest that many of the observations can be explained by viscoelasticity, specifically that a slow material response allows the pressure to remain high for long durations, which in turn allows growth of multiple bulges.

Mixtures of water with polyoxacyclobutane (POCB) have a unique phase diagram which combines liquid-liquid equilibrium (LLE) at high temperatures and cocrystallization of a POCB-hydrate at low temperatures. Such cocrystal hydrate formation is extremely rare among polymers. We report on the effects of adding NaCl salt on the phase behavior of POCB-water mixtures and the kinetics of hydrate crystallization from such mixtures. Salt loadings of less than 0.1 wt % were found to greatly expand the LLE region. Salt loadings of ∼10 wt % were found to significantly decrease the melting temperature of the hydrate below its ∼37 °C value under salt-free conditions. The hydrate was found to be remarkably tolerant of salt and persists at room temperature even when equilibrated with salt-saturated water. Salt was found to slow down hydrate crystallization, and the degree of slowing was greater than that expected from the salt-induced decrease in undercooling due to melting point depression.

While buckling is a time independent phenomenon for filaments or films bonded to soft elastic substrates, time evolution plays an important role when the substrate is a viscous fluid. Here we show that buckling instabilities in fluid-structure interactions can be reduced to the analysis of a growth function that amplifies the initial noise characterizing experimental or numerical error. The convolution between a specific growth function and noise leads to natural imperfections that emerge in the form of wave packets with a large scale modulation that can transform into localized structures depending on nonlinear effects. Specifically, we provide an experimental example where these wave packets are amplified into ridges for sufficiently low compression rates or are diluted into wrinkles for high compression rates.

Composites comprising crimped fibers of finite length embedded in a soft matrix have the potential to mimic the strain-hardening behavior of tissues containing fibrous collagen. Unlike continuous fiber composites, such chopped fiber composites would be flow-processable. Here, we study the fundamental mechanics of stress transfer between a single crimped fiber and the embedding matrix subjected to tensile strain. Finite element simulations show that fibers with large crimp amplitude and large relative modulus straighten significantly at small strain without bearing significant load. At large strain, they become taut and hence bear increasing load. Analogous to straight fiber composites, there is a region near the ends of each fiber which bears much lower stress than the midsection. We show that the stress-transfer mechanics can be captured by a shear lag model where the crimped fiber can be replaced with an equivalent straight fiber whose effective modulus is lower than that of the crimped fiber, but increases with applied strain. This allows estimating the modulus of a composite at low fiber fraction. The degree of strain hardening and the strain needed for strain hardening can be tuned by changing relative modulus of the fibers and the crimp geometry., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Surface instabilities are a versatile method for generating three-dimensional (3D) surface microstructure. When an elastomeric film weakly bonded to a substrate is swollen with solvent, buckle delamination and subsequent sliding of the film on the substrate lead to the formation of tall, self-contacting, and permanent folds. This paper explores the mechanics of fold development when such folding is induced by placing a drop on the surface of the film. We show that capillary effects can induce a strong coupling between folding and drop spreading: as folds develop, they wick the solvent toward the periphery of the drop, further propagating radially aligned folds. Accordingly, a solvent drop spreads far more on films that are weakly adhered to the substrate. As drop size reduces and folding becomes increasingly confined, debonding propagates along the perimeter of the wetted region, thus leading to corral-shaped fold patterns. On the other hand, as drop size increases and confinement effects weaken, isotropically oriented folds appear at a spacing that reduces as swelling increases. The spacing between the folds and the size of the corrals are both determined by the extent to which a single fold relieves compressive stress in its vicinity by sliding. We develop a model for folding which explicitly accounts for the fact that folds must initiate with near-zero volume under the buckle. The model shows that folds can appear even at very low swelling if there are large pre-existing debonded regions at the film-substrate interface.

Wrinkling is a ubiquitous surface phenomenon in many biological tissues and is believed to play an important role in arterial health. As arteries are highly nonlinear, anisotropic, multilayered composite systems, it is necessary to investigate wrinkling incorporating these material characteristics. Several studies have examined surface wrinkling mechanisms with nonlinear isotropic material relationships. Nevertheless, wrinkling associated with anisotropic constitutive models such as Ogden-Gasser-Holzapfel (OGH), which is suitable for soft biological tissues, and in particular arteries, still requires investigation. Here, the effects of OGH parameters such as fibers' orientation, stiffness, and dispersion on the onset of wrinkling, wrinkle wavelength and amplitude are elucidated through analysis of a bilayer system composed of a thin, stiff neo-Hookean membrane and a soft OGH substrate subjected to compression. Critical contractile strain at which wrinkles occur is predicted using both finite element analysis and analytical linear perturbation approach. Results suggest that besides stiffness mismatch, anisotropic features associated with fiber stiffness and distribution might be used in natural layered systems to adjust wrinkling and subsequent folding behaviors. Further analysis of a bilayer system with fibers in the (x-y) plane subjected to compression in the x direction shows a complex dependence of wrinkling strain and wavelength on fiber angle, stiffness, and dispersion. This behavior is captured by an approximation utilizing the linearized anisotropic properties derived from OGH model. Such understanding of wrinkling in this artery wall-like system will help identify the role of wrinkling mechanisms in biological artery in addition to the design of its synthetic counterparts.

Chronic inflammatory gastric reflux alters the esophageal microenvironment and induces metaplastic transformation of the epithelium, a precancerous condition termed Barrett's esophagus (BE). The microenvironmental niche, which includes the extracellular matrix (ECM), substantially influences cell phenotype. ECM harvested from normal porcine esophageal mucosa (eECM) was formulated as a mucoadhesive hydrogel, and shown to largely retain basement membrane and matrix-cell adhesion proteins. Dogs with BE were treated orally with eECM hydrogel and omeprazole ( n = 6) or omeprazole alone ( n = 2) for 30 days. eECM treatment resolved esophagitis, reverted metaplasia to a normal, squamous epithelium in four of six animals, and downregulated the pro-inflammatory tumor necrosis factor-α + cell infiltrate compared to control animals. The metaplastic tissue in control animals ( n = 2) did not regress. The results suggest that in vivo alteration of the microenvironment with a site-appropriate, mucoadhesive ECM hydrogel can mitigate the inflammatory and metaplastic response in a dog model of BE., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

We examine the stretching behavior of rubber-plastic composites composed of a layer of styrene-ethylene/propylene-styrene (SEPS) rubber, bonded to a layer of linear low density polyethylene (LLDPE) plastic. Dog-bone shaped samples of rubber, plastic, and rubber-plastic bilayers with rubber : plastic thickness ratio in the range of 1.2-9 were subjected to uniaxial tension tests. The degree of inhomogeneity of deformation was quantified by digital image correlation analysis of video recordings of these tests. In tension, the SEPS layer showed homogeneous deformation, whereas the LLDPE layer showed necking followed by stable drawing owing to its elastoplastic deformation behavior and post-yield strain hardening. Bilayer laminates showed behavior intermediate between the plastic and the rubber, with the degree of necking and drawing reducing as the rubber : plastic ratio increased. A simple model was developed in which the force in the bilayer was taken as the sum of forces in the plastic and the rubber layers measured independently. By applying a mechanical energy balance to this model, the changes in bilayer necking behavior with rubber thickness could be predicted qualitatively.

We examine the effect of composition on the morphology of a ternary mixture comprising two molten polymeric liquid phases (polyisobutylene and polyethylene oxide) and micron-scale spherical silica particles. The silica particles were treated with silanes to make them partially wetted by both polymers. Particle loadings up to 30 vol% are examined while varying the fluid phase ratios across a wide range. Numerous effects of particle addition are catalogued, stabilization of Pickering emulsions and of interfacially-jammed co-continuous microstructures, meniscus-bridging of particles, particle-induced coalescence of the dispersed phase, and significant shifts in the phase inversion composition. Many of the effects are asymmetric, for example particle-induced coalescence is more severe and drop sizes are larger when polyisobutylene is the continuous phase, and particles promote phase continuity of the polyethylene oxide. These asymmetries are likely attributable to a slight preferential wettability of the particles towards the polyethylene oxide. A state map is constructed which classifies the various microstructures within a triangular composition diagram. Comparisons are made between this diagram vs. a previous one constructed for the case when particles are fully-wetted by polyethylene oxide.

Gastrointestinal pathologies, injuries, and defects affect millions of individuals each year. While there are diverse treatment options for these individuals, no ideal solution exists. The repair or replacement of gastrointestinal tissue, therefore, represents a large unmet clinical need. Biomaterials derived from extracellular matrix (ECM) scaffolds have been effectively used to repair or replace numerous tissues throughout the body in both preclinical and clinical studies. Such scaffolds are prepared from decellularized tissues, and the biochemical, structural, and biologic properties vary depending upon the source tissue from which the ECM is derived. Given the potential benefit of a site-specific ECM scaffold for some applications, the objective of this study was to prepare, characterize, and determine the in vitro and in vivo cell response to ECM derived from porcine colon. Results of this study show that porcine colon can be effectively decellularized while retaining biochemical and structural constituents of the source tissue. Two forms of colonic ECM, scaffold and hydrogel, were shown to be cell friendly and facilitate the polarization of macrophages toward an M2 phenotype both in vitro and in vivo. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 291-306, 2017., (© 2015 Wiley Periodicals, Inc.)

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed., Statement of Significance: More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

We examine the mechanics of three-layer composite films composed of an elastomeric layer sandwiched between two thin surface layers of plastic. Upon stretching and releasing such composite films, they develop a highly wrinkled surface texture. The mechanism for this texturing is that during stretching, the plastic layers yield and stretch irreversibly whereas the elastomer stretches reversibly. Thus upon releasing, the plastic layers buckle due to compressive stress imposed by the elastomer. Experiments are conducted using SEPS elastomer and 50 micron thick LLDPE plastic films. Stretching and releasing the composites to 2-5 times their original length induces buckles with wavelength on the order of 200 microns, and the wavelength decreases as the stretching increases. FEM simulations reveal that plastic deformation is involved at all stages during this process: (1) during stretching, the plastic layer yields in tension; (2) during recovery, the plastic layer first yields in-plane in compression and then buckles; (3) post-buckling, plastic hinges are formed at high-curvature regions. Homogeneous wrinkles are predicted only within a finite window of material properties: if the yield stress is too low, the plastic layers yield in-plane, without wrinkling, whereas if the yield stress is too high, non-homogeneous wrinkles are predicted. This approach to realizing highly wrinkled textures offers several advantages, most importantly the fact that high aspect ratio wrinkles (amplitude to wavelength ratios exceeding 0.4) can be realized.

Ternary mixtures composed of polyisobutylene (PIB), polyethylene oxide (PEO), and silica particles yield three distinct open-pore morphologies depending on the mixture composition: (1) pendular network (particles bonded together by menisci of PEO); (2) capillary aggregate network (particles and PEO form a combined phase with strongly solid-like properties which forms a percolating network); (3) cocontinuous morphology (silica and the PEO form a highly viscous combined phase which retards interfacial tension-driven coarsening). Remarkably, interfacial tension plays altogether different roles in stabilizing these three morphologies: stabilizing the first, not affecting the second, and destabilizing the last. The first two of these morphologies appear to be generalizable to other systems, e.g. to oil/water/particle mixtures. In all three cases, the pores do not collapse even after flow, i.e. all three porous morphologies are amenable to processing.

The equilibrium structures of ternary oil/water/surfactant systems are often represented within a triangular composition diagram with various regions of the triangle corresponding to different equilibrium states. We transplant this idea to ternary liquid/fluid/particle systems that are far from equilibrium. Liquid/liquid/particle mixtures or liquid/gas/particle mixtures yield a wide diversity of morphologies including Pickering emulsions, bijels, pendular aggregates, spherical agglomerates, capillary suspensions, liquid marbles, powdered liquids, and particle-stabilized foams. This paper argues that such ternary liquid/fluid/particle mixtures can be unified into a non-equilibrium state diagram. What is common among all these systems is that the morphology results from an interplay between the preferential wettability of the particles, capillarity, and viscous forces encountered during mixing. Therefore all such systems share certain universal features, regardless of the details of the particles or fluids used. These features guide the construction of a non-equilibrium state diagram which takes the form of a triangular prism, where each triangular cross-section of the prism corresponds to a different relative affinity of the particles towards the two fluids. We classify the prism into regions in which the various morphologies appear and also emphasize the major difference between systems in which the particles are fully-wetted by one of the fluids vs. partially-wetted by both fluids. We also discuss how the state diagram may change with mixing intensity or with interparticle attractions.

Biomaterials composed of mammalian extracellular matrix (ECM) promote constructive tissue remodeling with minimal scar tissue formation in many anatomical sites. However, the optimal shape and form of ECM scaffold for each clinical application can vary markedly. ECM hydrogels have been shown to promote chemotaxis and differentiation of neuronal stem cells, but minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form. These ECM materials can be manufactured to exist in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. Implantation into the lesion cavity after a stroke could hence provide a means to support endogenous repair mechanisms. Herein, we characterize the rheological properties of an ECM hydrogel composed of urinary bladder matrix (UBM) that influence its delivery and in vivo interaction with host tissue. There was a notable concentration-dependence in viscosity, stiffness, and elasticity; all characteristics important for minimally invasive intracerebral delivery. An efficient MRI-guided injection with drainage of fluid from the cavity is described to assess in situ hydrogel formation and ECM retention at different concentrations (0, 1, 2, 3, 4, and 8mg/mL). Only ECM concentrations >3mg/mL gelled within the stroke cavity. Lower concentrations were not retained within the cavity, but extensive permeation of the liquid phase ECM into the peri-infarct area was evident. The concentration of ECM hydrogel is hence an important factor affecting gelation, host-biomaterial interface, as well intra-lesion distribution., Statement of Significance: Extracellular matrix (ECM) hydrogel promotes constructive tissue remodeling in many tissues. Minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form that exists in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. We here report the rheological characterization of an injectable ECM hydrogel and its concentration-dependent delivery into a lesion cavity formed after a stroke based on MRI-guidance. The concentration of ECM determined its retention within the cavity or permeation into tissue and hence influenced its interaction with the host brain. This study demonstrates the importance of understanding the structure-function relationship of biomaterials to guide particular clinical applications., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

We report two-dimensional (2D) photonic crystal (PC) sensing materials that selectively detect Candida albicans (C. albicans). These sensors utilize Concanavalin A (Con A) protein hydrogels with a 2D PC embedded on the Con A protein hydrogel surface, that multivalently and selectively bind to mannan on the C. albicans cell surface to form crosslinks. The resulting crosslinks shrink the Con A protein hydrogel, reduce the 2D PC particle spacing, and blue-shift the light diffracted from the PC. The diffraction shifts can be visually monitored, measured with a spectrometer, or determined from the Debye diffraction ring diameter. Our unoptimized hydrogel sensor has a detection limit of around 32 CFU/mL for C. albicans. This sensor distinguishes between C. albicans and those microbes devoid of cell-surface mannan such as the gram-negative bacterium E. coli. This sensor provides a proof-of-concept for utilizing recognition between lectins and microbial cell surface carbohydrates to detect microorganisms in aqueous environments., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We examine the buckling of a thin elastic film floating on a viscous liquid layer which is itself supported on a prestretched rubber sheet. Releasing the prestretch in the rubber induces a viscous stress in the liquid, which in turn induces a compressive stress in the elastic film, leading to buckling. Unlike many previous studies on wrinkling of floating films, the buckling process in the present study is dominated by viscous effects whereas gravitational effects are negligible. An approximate shear lag model predicts the evolution of the stress profile in the unbuckled film that depends on three parameters: the rate at which the prestretch is released, the thickness of the liquid layer, and the length of the elastic film. A linear perturbation analysis is developed to predict the wavelength of wrinkles. Numerical simulations are conducted to predict nonlinear evolution of the wrinkle wavelength and amplitude. Experiments using elastic polymer films and viscous polymer liquids show trends that are qualitatively consistent with the predictions although quantitatively, the experimentally-observed wrinkle wavelengths are longer than predicted. Although this article is focused only on small-strain wrinkling behavior, we show that application of large nominal strains (on the order of 100%) leads to sharply localized folds. Thus this approach may be useful for developing buckled features with high aspect ratio on surfaces.

We investigate capillary bridging-induced gelation phenomena in silica particle suspensions and pastes, where a particle-wetting fluid is added as the third component. Increasing the wetting fluid loading in the ternary system induces a morphological transition from a pendular network to compact capillary aggregates network, with an intermediate funicular state. To our knowledge, the formation of percolated structures from compact capillary aggregates when the volume fraction of a wetting fluid approaches that of the particles is unprecedented. Such structures appear to result from the arrested coalescence of compact capillary aggregates due to the balance between the Laplace pressure and solid-like properties (yield stress, elasticity) of the aggregates. Shear-induced yielding of the ternary systems, linked to their percolating nature, is strongly influenced by the amount of wetting fluid phase. A non-monotonic dependence of the yield stress on the amount of wetting fluid is found, with the maximum yield stress obtained for a wetting fluid-to-particle volume fraction ratio of 0.2-0.3. For pendular systems, linear viscoelastic properties display a soft glassy rheological behavior above the percolation threshold (around 4 vol% particles), and complex viscosity data can be scaled using the high frequency plateau value, as well as a single characteristic relaxation time, which decreases when the particle concentration is increased. In addition, the particle concentration dependence of the yielding transition in the pendular regime appears to be efficiently described by two parameters extracted from the steady state flow curves: the yield stress and the limiting viscosity at a high shear rate. Although these non-colloidal networks result from flow-driven assembly, the scaling laws for our pendular gels are reminiscent of colloidal gels with a fractal geometry. Our studies pinpoint new pathways to create physical gels where the interparticle attraction strength is determined by capillary interactions.

A major component of cephalopod adaptive camouflage behavior has rarely been studied: their ability to change the three-dimensionality of their skin by morphing their malleable dermal papillae. Recent work has established that simple, conical papillae in cuttlefish (Sepia officinalis) function as muscular hydrostats; that is, the muscles that extend a papilla also provide its structural support. We used brightfield and scanning electron microscopy to investigate and compare the functional morphology of nine types of papillae of different shapes, sizes and complexity in six species: S. officinalis small dorsal papillae, Octopus vulgaris small dorsal and ventral eye papillae, Macrotritopus defilippi dorsal eye papillae, Abdopus aculeatus major mantle papillae, O. bimaculoides arm, minor mantle, and dorsal eye papillae, and S. apama face ridge papillae. Most papillae have two sets of muscles responsible for extension: circular dermal erector muscles arranged in a concentric pattern to lift the papilla away from the body surface and horizontal dermal erector muscles to pull the papilla's perimeter toward its core and determine shape. A third set of muscles, retractors, appears to be responsible for pulling a papilla's apex down toward the body surface while stretching out its base. Connective tissue infiltrated with mucopolysaccharides assists with structural support. S. apama face ridge papillae are different: the contraction of erector muscles perpendicular to the ridge causes overlying tissues to buckle. In this case, mucopolysaccharide-rich connective tissue provides structural support. These six species possess changeable papillae that are diverse in size and shape, yet with one exception they share somewhat similar functional morphologies. Future research on papilla morphology, biomechanics and neural control in the many unexamined species of octopus and cuttlefish may uncover new principles of actuation in soft, flexible tissue.

We report that a variety of ternary particle/liquid/liquid mixtures heavily aggregate or separate completely if (1) the particles are fully or almost fully wetted by one fluid, and (2) if the wetting fluid volume fraction is comparable to the particle volume fraction. Aggregation and separation do not happen if the particles are partially wetted by both fluids, in which case Pickering emulsions appear at all compositions. Rheological and geometric criteria for aggregation are proposed and compared with a state diagram of a ternary system composed of oil, water, and hydrophilic glass particles. Analogies are drawn to wet granulation and spherical agglomeration, two particle processing operations in which wetting phenomena are important.

Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of in vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote in vivo axonal repair., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The ECM of mammalian tissues has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. Such scaffolds are prepared in many forms including sheets, powders, and hydrogels. ECM hydrogels provide advantages such as injectability, the ability to fill an irregularly shaped space, and the inherent bioactivity of native matrix. However, material properties of ECM hydrogels and the effect of these properties upon cell behavior are neither well understood nor controlled. The objective of this study was to prepare and determine the structure, mechanics, and the cell response in vitro and in vivo of ECM hydrogels prepared from decellularized porcine dermis and urinary bladder tissues. Dermal ECM hydrogels were characterized by a more dense fiber architecture and greater mechanical integrity than urinary bladder ECM hydrogels, and showed a dose dependent increase in mechanical properties with ECM concentration. In vitro, dermal ECM hydrogels supported greater C2C12 myoblast fusion, and less fibroblast infiltration and less fibroblast mediated hydrogel contraction than urinary bladder ECM hydrogels. Both hydrogels were rapidly infiltrated by host cells, primarily macrophages, when implanted in a rat abdominal wall defect. Both ECM hydrogels degraded by 35 days in vivo, but UBM hydrogels degraded more quickly, and with greater amounts of myogenesis than dermal ECM. These results show that ECM hydrogel properties can be varied and partially controlled by the scaffold tissue source, and that these properties can markedly affect cell behavior., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

When a polymer film that is weakly attached to a rigid substrate is exposed to solvent, swelling-induced compressive stress nucleates buckle delamination of the film from the substrate. Surprisingly, the buckles do not have a sinusoidal profile, instead, the film near the delamination buckles slides toward the buckles causing growth of sharp folds of high aspect ratio. These folds do not result from a wrinkle-to-fold transition; instead, the film goes directly from a flat state to a folded state. The folds persist even after the solvent evaporates. We propose that patterned delamination and folding may be exploited to realize high-aspect ratio topological features on surfaces through control of a set of boundary constraints arising from the interrelation of film-surface adhesion, film thickness and degree of swellabilty., (© 2011 American Chemical Society)

When particles adsorb at a fluid/fluid interface at a sufficiently high concentration, the interface loses mobility and displays solidlike characteristics, a phenomenon called "interfacial jamming". Jamming can arrest interfacial tension-driven morphological coarsening in liquid/liquid or gas/liquid systems and therefore stabilize two phase morphologies with unusual interfacial shapes, for example, nonspherical drops and bubbles, and bijels. Here, we conduct a systematic study of interfacial tension-driven jamming of a particle monolayer using a spinning drop tensiometer (SDT). A drop of mineral oil surrounded by ethylene glycol was spun into a cylindrical shape in a SDT. With decreasing rotational rate, the cylindrical drop retracted due to interfacial tension, thus reducing the interfacial area. In the case of particle-covered drops, drop retraction caused an increase in interfacial particle concentration. Accordingly, when the specific interfacial area became comparable to that of a close packing of particles, interfacial jamming occurred and drop retraction was arrested. Fast interfacial contraction or low particle loadings led to less compact jammed monolayers, that is, with a larger specific interfacial area. There was also significant hysteresis between compressing versus expanding the jammed monolayer, suggesting that a certain minimum stress is required for unjamming. Limited experiments with the same particles at a mineral oil/silicone oil interface showed altogether different behavior. In this case, particles did not spread at the interface and a particle-free portion of the interface coexisted with a particle-covered portion. This suggests that the monolayer behavior at this nonpolar/nonpolar interface is dominated by interparticle attraction.

This paper reports a novel, physiologically significant, microfluidic phenomenon generated by nanomolar concentrations of drag-reducing polymers (DRP) dissolved in flowing blood, which may explain previously demonstrated beneficial effects of DRP on tissue perfusion. In microfluidic systems used in this study, DRP additives were found to significantly modify traffic of red blood cells (RBC) into microchannel branches as well as reduce the near-wall cell-free layer, which normally is found in microvessels with a diameter smaller than 0.3 mm. The reduction in plasma layer size led to attenuation of the so-called "plasma skimming" effect at microchannel bifurcations, increasing the number of RBC entering branches. In vivo, these changes in RBC traffic may facilitate gas transport by increasing the near vessel wall concentration of RBC and capillary hematocrit. In addition, an increase in near-wall viscosity due to the redirection of RBC in this region may potentially decrease vascular resistance as a result of increased wall shear stress, which promotes endothelium mediated vasodilation. These microcirculatory phenomena can explain the previously reported beneficial effects of DRP on hemodynamics in vivo observed in many animal studies. We also report here our finding that DRP additives reduce flow separations at microchannel expansions, deflecting RBC closer to the wall and eliminating the plasma recirculation zone. Although the exact mechanism of the DRP effects on RBC traffic in microchannels is yet to be elucidated, these findings may further DRP progress toward clinical use.

The effects of surfactants on the interfacial tension driven retraction of elongated drops were studied in a spinning drop tensiometer. Experiments were conducted on polypropylene glycol (PPG) drops suspended in polyethylene glycol (PEG), with Pluronic block copolymers as surfactants. Two unusual observations are reported here. In the first, initially-elongated drops generated at high rotational speed were allowed to retract by reducing the rotational speed. Pluronic-laden drops would not retract completely, but would instead maintain strongly nonspherical shapes indefinitely. We attribute such "nonretraction" to an interfacial yield stress induced by the Pluronic surfactant. In the second, drops being heated while spinning at a constant speed would elongate sharply at some temperature, and subsequently breakup. Such "autoextension" and breakup indicate complex nonmonotonic changes in interfacial tension with time during heating. We propose that autoextension occurs because at low temperature, interfacially-adsorbed surfactant is crystallized and hence trapped at the interface at a concentration far above equilibrium.

Biologic scaffolds composed of extracellular matrix (ECM) have been used to facilitate the repair and reconstruction of a variety of tissues in clinical and pre-clinical studies. The clinical utility of such scaffolds can be limited by the geometric and mechanical properties of the tissue or organ from which the ECM is harvested. An injectable gel form of ECM could potentially conform to any three-dimensional shape and could be delivered to sites of interest by minimally invasive techniques. The objectives of the present study were to prepare a gel form of ECM harvested from the urinary bladder (urinary bladder matrix or UBM), to characterize the rheological properties of the gel, and finally to evaluate the ability of the gel to support in vitro growth of smooth muscle cells. Following enzymatic solubilization with pepsin, UBM was induced to self-assemble into a gel when brought to physiological conditions. The UBM gel supported the adhesion and growth of rat aortic smooth muscle cells when cultured under static in vitro conditions. The present study showed that an intact form of UBM can be successfully solubilized without purification steps and induced to repolymerize into a gel form of the UBM biologic scaffold material.

Natural and synthetic soluble drag reducing polymers (DRP) have been shown to produce beneficial effects on blood circulation in various animal models and may represent a novel bioengineering way to treat cardiovascular disorders. These polymers are known to degrade when subjected to high shear stresses which could be a part of the process of their elimination from the vascular system. However, the relative rate of their degradation was not known especially in the presence of blood cells or particles. The hydrodynamic tests in this study demonstrated that DRP mechanical degradation was significantly increased by the presence of red blood cells (RBC) and even more so by the presence of rigid particles of similar size. Degradation rates increased with an increase in RBC or particle concentration. The natural DRP (derived from aloe) was shown to be much more resistant to flow-induced degradation than polyethylene oxide in the presence or absence of RBC.

Based upon the crystal structures of PcrA helicase, we have made and characterised mutations in a number of conserved helicase signature motifs around the ATPase active site. We have also determined structures of complexes of wild-type PcrA with ADPNP and of a mutant PcrA complexed with ADPNP and Mn2+. The kinetic and structural data define roles for a number of different residues in and around the ATP binding site. More importantly, our results also show that there are two functionally distinct conformations of ATP in the active site. In one conformation, ATP is hydrolysed poorly whereas in the other (activated) conformation, ATP is hydrolysed much more rapidly. We propose a mechanism to explain how the stimulation of ATPase activity afforded by binding of single-stranded DNA stabilises the activated conformation favouring Mg2+binding and a consequent repositioning of the gamma-phosphate group which promotes ATP hydrolysis. A part of the associated conformational change in the protein forces the side-chain of K37 to vacate the Mg2+binding site, allowing the cation to bind and interact with ATP., (Copyright 1999 Academic Press.)

We have determined two different structures of PcrA DNA helicase complexed with the same single strand tailed DNA duplex, providing snapshots of different steps on the catalytic pathway. One of the structures is of a complex with a nonhydrolyzable analog of ATP and is thus a "substrate" complex. The other structure contains a bound sulphate ion that sits in a position equivalent to that occupied by the phosphate ion produced after ATP hydrolysis, thereby mimicking a "product" complex. In both complexes, the protein is monomeric. Large and distinct conformational changes occur on binding DNA and the nucleotide cofactor. Taken together, these structures provide evidence against an "active rolling" model for helicase action but are instead consistent with an "inchworm" mechanism.