Effect of Porous Substrate Topographies on Cell Dynamics: A Computational Study.

Controlling cell-substrate interactions via the microstructural characteristics of biomaterials offers an advantageous path for modulating cell dynamics, mechanosensing, and migration, as well as for designing immune-modulating implants, all without the drawbacks of chemical-based triggers. Specifically, recent in vivo studies have suggested that a porous implant's microscale curvature landscape can significantly impact cell behavior and ultimately the immune response. To investigate such cell-substrate interactions, we utilized a 3D computational model incorporating the minimum necessary physics of cell migration and cell-substrate interactions needed to replicate known in vitro behaviors. This model specifically incorporates the effect of membrane tension, which was found to be necessary to replicate in vitro cell behavior on curved surfaces. Our simulated substrates represent two classes of porous materials recently used in implant studies, which have markedly different microscale curvature distributions and pore geometries. We found distinct differences between the overall migration behaviors, shapes, and actin polymerization dynamics of cells interacting with the two substrates. These differences were correlated to the shape energy of the cells as they interacted with the porous substrates, in effect interpreting substrate topography as an energetic landscape interrogated by cells. Our results demonstrate that microscale curvature directly influences cell shape and migration and, therefore, is likely to influence cell behavior. This supports further investigation of the relationship between the surface topography of implanted materials and the characteristic immune response, a complete understanding of which would broadly advance principles of biomaterial design.

Enhanced Capillary Wicking through Hierarchically Porous Constructs Derived from Bijel Templates.

Liquid capillarity through porous media can be enhanced by a rational design of hierarchically porous constructs that suggest sufficiently large liquid pathways from an upper-level hierarchy as well as capillary pressure enabled by a lower hierarchy. Here, we demonstrate a material design strategy utilizing a new class of self-assembled soft materials, called bicontinuous interfacially jammed emulsion gels (bijels), to produce hierarchically porous copper, which enables the unique combination of unprecedented control over both macropores and mesopores in a regular, uniform, and continuous arrangement. The dynamic droplet topologies on the hierarchically copper pores prove the significant enhancement in liquid capillarity compared to homogeneous porous structures. The role of nanoscale morphology in liquid infiltration is further investigated through environmental scanning electron microscopy, in which wetting through the mesopores occurs at the beginning, followed by liquid transport through macropores. This understanding on capillary wicking will allow us to design better hierarchically porous media that can address performance breakthroughs in interfacial applications, ranging from battery electrodes, cell delivery in biomedical devices, to capillary-fed thermal management systems.

Bijel rheology reveals a 2D colloidal glass wrapped in 3D.

We present rheological evidence demonstrating the glass-like nature of bicontinuous interfacially jammed emulsion gels (bijels). Under small amplitude oscillatory shear, bijels exhibited rheological signatures akin to α and ß relaxation that are also invariable to interfacial tension changes, behaviors which are reminiscent of caged particle dynamics found in colloidal glasses, and well described by a previously reported adaptation of mode-coupling theory for colloidal glass rheology. Guided by their rheological signatures and supported by particle detachment and attraction energy approximations, we rationalize that bijels can be represented as 2-dimensional (2D) colloidal glasses that percolate in 3-dimensional (3D) space, and attractive interactions are not required for their stability. To provide further support for this conjecture, we qualitatively compare the rheology of bijels and a capillary suspension that is stabilized by strong, rigid capillary bridges between the particles, beyond their limit of linear viscoelasticity. Our results demonstrate that the strong adsorption of particles to the continuous interface and the lack of strong attractive interparticle forces enable recovery by interfacial tension into new jammed configurations after shear deformation. These behaviors are qualitatively different from those in the capillary suspension, where the breaking of attractive interparticle bonds results in dramatic changes to the microstructure and rheology over a narrow range of shear amplitudes. Our findings unveil bijels as 2D colloidal glasses weaving in 3D space and establish that interparticle attractions are not required for stability in bijels, and interfacial jamming alone is sufficient to impart viscoelasticity and gel-like rheology to these materials.

Mitigating Bubble Traffic in Gas-Evolving Electrodes via Spinodally Derived Architectures.

Porous electrodes are widely used in the industry because of their high surface area to volume ratio. However, the stochastic morphology of most commercially available porous electrodes results in poor electrical connections in the solid phase and inefficient mass transport through the pore phase. This can be especially detrimental for gas-evolving processes such as water electrolysis for hydrogen and oxygen generation. Bicontinuous interfacially jammed emulsion gels (bijels) offer templates from which to create porous electrodes with robust solid-state interconnectivity and a uniform pore structure that facilitate improved electron and mass transport. In this study, gas release rates and electrochemical experiments are utilized to study the effects of powder- and bijel-derived microstructures on hydrogen generation by water electrolysis. The bijel-derived electrodes are shown to expel product gas faster and require up to 25% less overpotential to drive water electrolysis over the range of current densities tested (-5 to -40 mA/cm2) than their powder-derived analogs. Our findings suggest that the uniform and bicontinuous domains of bijel-derived porous electrodes can mitigate the limited current distribution and deleterious bubble effect found in stochastic electrodes, in turn improving the overall performance of electrolytic processes requiring transport of gaseous species.

Laser cavitation rheology for measurement of elastic moduli and failure strain within hydrogels.

We introduce laser cavitation rheology (LCR) as a minimally-invasive optical method to characterize mechanical properties within the interior of biological and synthetic aqueous soft materials at high strain-rates. We utilized time-resolved photography to measure cavitation bubble dynamics generated by the delivery of focused 500 ps duration laser radiation at λ = 532 nm within fibrin hydrogels at pulse energies of Ep = 12, 18 µJ and within polyethylene glycol (600) diacrylate (PEG (600) DA) hydrogels at Ep = 2, 5, 12 µJ. Elastic moduli and failure strains of fibrin and PEG (600) DA hydrogels were calculated from these measurements by determining parameter values which provide the best fit of the measured data to a theoretical model of cavitation bubble dynamics in a Neo-Hookean viscoelastic medium subject to material failure. We demonstrate the use of this method to retrieve the local, interior elastic modulus of these hydrogels and both the radial and circumferential failure strains.

Boiling Heat Transfer with a Well-Ordered Microporous Architecture.

Boiling heat transfer through a porous medium offers an attractive combination of enormous liquid-vapor interfacial area and high bubble nucleation site density. In this work, we characterize the boiling performances of porous media by employing the well-ordered and highly interconnected architecture of inverse opals (IOs). The boiling characterization identifies hydrodynamic mechanisms through which structural characteristics affect the boiling performance of metallic microporous architecture by validating empirical measurements. The boiling performances can be optimized through the rational design of both the structural thicknesses and pore diameters of IOs, which demonstrate up to 336% enhancement in boiling heat-transfer coefficient (HTC) over smooth surfaces. The optimal HTC and critical heat flux occur at approximately 3-4 µm in porous structure thickness, which is manifested through the balance of liquid-vapor occupation within the spatial confinement of the IO structure. The optimization of boiling performances with varying pore diameters (0.3-1.0 µm) can be attributed to the hydraulic competitions between permeability and viscous resistance to liquid-vapor transport. This study unveils thermophysical understandings to enhance multiphase heat transfer in microporous media for ultrahigh heat flux thermal management.

Impact of Particle Size on Droplet Coalescence in Solid-Stabilized High Internal Phase Emulsions.

High internal phase emulsions (HIPEs) comprise highly faceted droplets separated by thin films of fluid. Though surfactants are traditionally used in formulating HIPEs, growing interest in solid-stabilized HIPEs calls for a better understanding of how particles may affect the coalescence of droplets at high volume fractions of the dispersed phase. In this study, we address the effect of particle size on this issue. Using confocal microscopy, we examine the microstructures of four different solid-stabilized emulsion series and quantify droplet coalescence in each. We show that, systematically, HIPEs stabilized with smaller particles show a greater propensity for film rupture and the presence of partially coalesced droplets, whereas the use of larger particles results in a higher fraction of bridged particle monolayers between neighboring droplets. This result is in contrast with the behavior of dilute emulsions, where the use of smaller particles has been shown to impart greater stability against droplet coalescence. Utilizing a simple model of film rupture, we rationalize our experimental findings in the context of the capillary pressure profile within a solid-stabilized liquid film, and show that bridged monolayer formation is directly linked to improved film stability at high volume fractions of the dispersed phase. Therefore, particle size can impact the stability of solid-stabilized HIPEs by influencing their propensity for monolayer formation.

Bijel-templated implantable biomaterials for enhancing tissue integration and vascularization.

Mitigation of the foreign body response (FBR) and successful tissue integration are essential to ensuring the longevity of implanted devices and biomaterials. The use of porous materials and coatings has been shown to have an impact, as the textured surfaces can mediate macrophage interactions with the implant and influence the FBR, and the pores can provide space for vascularization and tissue integration. In this study, we use a new class of implantable porous biomaterials templated from bicontinuous interfacially jammed emulsion gels (bijels), which offer a fully percolating, non-constricting porous network with a uniform pore diameter on the order of tens of micrometers, and surfaces with consistent curvature. We demonstrate that these unique morphological features, inherent to bijel-templated materials (BTMs), can enhance tissue integration and vascularization, and reduce the FBR. Cylindrical polyethylene glycol diacrylate (PEGDA) BTMs, along with PEGDA particle-templated materials (PTMs), and non-templated materials (NTMs), were implanted into the subcutaneous space of athymic nude mice. After 28 days, implants were retrieved and analyzed via histological techniques. Within BTMs, blood vessels of increased size and depth, changes in collagen deposition, and increased presence of pro-healing macrophages were observed compared to that of PTM and NTM implants. Bijel templating offers a new route to biomaterials that can improve the function and longevity of implantable devices. STATEMENT OF SIGNIFICANCE: All implanted biomaterials are subject to the foreign body response (FBR) which can have a detrimental effect on their efficacy. Altering the surface chemistry can decrease the FBR by limiting the amount of proteins adsorbed to the implant. This effect can be enhanced by including pores in the biomaterial to allow new tissue growth as the implant becomes integrated in the body. Here, we introduce a new class of self-assembled biomaterials comprising a fully penetrating, non-constricting pore phase with hyperbolic (saddle) surfaces for enhanced tissue integration. These unique morphological characteristics result in dense blood vessel formation and favorable tissue response properties demonstrated in a four-week implantation study.

Role of particles in the rheology of solid-stabilized high internal phase emulsions.

HYPOTHESIS: The presence of colloidal particles on fluid interfaces can have a significant impact on the rheology of solid-stabilized high internal phase emulsions (HIPEs). EXPERIMENTS: Using dynamic oscillatory rheometry and confocal microscopy, we investigate a broad array of solid-stabilized HIPEs formulated along four different compositional trajectories in their ternary state diagram, using particles of three different sizes and two different surface chemistries. FINDINGS: We unveil three important consequences of the use of particles, in lieu of surfactants, on the rheology of HIPEs. First, particle excluded volume interactions take a pronounced role in the transition to solid-like rheology due to crowding. An effective dispersed phase volume fraction, taking into account the particle three-phase contact angle, must be defined to account for the dependence of the mixture's rheology on its composition. Second, weak, chemistry-dependent attractive colloidal interactions through the continuous phase result in a finite elastic modulus at low effective dispersed phase volume fractions. Third, we observe a secondary rise in the mixture's elastic modulus at increasingly high dispersed-to-continuous-phase volumetric ratios. We postulate these interactions stem from attractive lateral capillary interactions between the particles, due to thinning of the continuous fluid film between faceted droplets.

Scalable synthesis of gyroid-inspired freestanding three-dimensional graphene architectures.

Three-dimensional porous architectures of graphene are desirable for energy storage, catalysis, and sensing applications. Yet it has proven challenging to devise scalable methods capable of producing co-continuous architectures and well-defined, uniform pore and ligament sizes at length scales relevant to applications. This is further complicated by processing temperatures necessary for high quality graphene. Here, bicontinuous interfacially jammed emulsion gels (bijels) are formed and processed into sacrificial porous Ni scaffolds for chemical vapor deposition to produce freestanding three-dimensional turbostratic graphene (bi-3DG) monoliths with high specific surface area. Scanning electron microscopy (SEM) images show that the bi-3DG monoliths inherit the unique microstructural characteristics of their bijel parents. Processing of the Ni templates strongly influences the resultant bi-3DG structures, enabling the formation of stacked graphene flakes or fewer-layer continuous films. Despite the multilayer nature, Raman spectra exhibit no discernable defect peak and large relative intensity for the Raman 2D mode, which is a characteristic of turbostratic graphene. Moiré patterns, observed in scanning tunneling microscopy images, further confirm the presence of turbostratic graphene. Nanoindentation of macroscopic pillars reveals a Young's modulus of 30 MPa, one of the highest recorded for sp2 carbon in a porous structure. Overall, this work highlights the utility of a scalable self-assembly method towards porous high quality graphene constructs with tunable, uniform, and co-continuous microstructure.

Composite bijel-templated hydrogels for cell delivery.

Numerous processing techniques aim to impart interconnected, porous structures within regenerative medicine materials to support cell delivery and direct tissue growth. Many of these techniques lack predictable control of scaffold architecture, and rapid prototyping methods are often limited by time-consuming, layer-by-layer fabrication of micro-features. Bicontinuous interfacially jammed emulsion gels (bijels) offer a robust, self-assembly-based platform for synthesizing a new class of morphologically unique cell delivery biomaterials. Bijels form via kinetic arrest of temperature-driven spinodal decomposition in partially miscible binary liquid systems. These non-equilibrium soft materials are comprised of co-continuous, fully percolating, non-constricting liquid domains separated by a nanoparticle monolayer. Through the selective introduction of biocompatible precursors, hydrogel scaffolds displaying the morphological characteristics of the parent bijel can be formed. We report using bijel templating to generate structurally unique, fibrin-loaded polyethylene glycol hydrogel composites. Demonstration of composite bijel-templated hydrogels (CBiTHs) as a new cell delivery system was carried out in vitro using fluorescence-based tracking of cells delivered to previously acellular fibrin gels. Imaging analysis confirmed repeatable delivery of normal human dermal fibroblasts to acellular fibrin gels.

Evaluation of Heating and Shearing on the Viscoelastic Properties of Calcium Hydroxyapatite Used in Injection Laryngoplasty.

OBJECTIVE: To compare the viscoelastic properties of calcium hydroxyapatite (CaHA) to carboxymethylcellulose (CMC) injectables used for injection laryngoplasty and determine if they are affected by heating and shearing. STUDY DESIGN: Experimental. SETTING: University laboratory. SUBJECTS AND METHODS: Vocal fold injection laryngoplasty with CaHA is oftentimes challenging due to the amount of pressure necessary to push the injectate through a needle. Anecdotal techniques, such as heating the product, have been suggested to facilitate injection. The viscoelastic properties of CaHA and CMC were measured with a rheometer. The effects of heating and shearing on sample viscoelasticity were recorded. RESULTS: CaHA was 9.5 times more viscous than CMC (43,100 vs 4540 Pa·s). Heating temporarily decreased the viscosity of CaHA by 32%. However, it also caused the viscosity to subsequently increase after time. Shearing of CaHA reduced its viscosity by 26%. Heating and shearing together temporarily reduced the viscosity of CaHA by 52%. CONCLUSION: A combination of heating and shearing had a more profound effect than heating or shearing alone on the viscosity of CaHA, potentially making it easier to inject temporarily. Long-term and in vivo studies are required to further analyze the effect of heating and shearing on CaHA injectables.

Expanding functionality of recombinant human collagen through engineered non-native cysteines.

Collagen is the most abundant protein in extracellular matrices and is commonly used as a tissue engineering scaffold. However, collagen and other biopolymers from native sources can exhibit limitations when tuning mechanical and biological properties. Cysteines do not naturally occur within the triple-helical region of any native collagen. We utilized a novel modular synthesis strategy to fabricate variants of recombinant human collagen that contained 2, 4, or 8 non-native cysteines at precisely defined locations within each biopolymer. This bottom-up approach introduced capabilities using sulfhydryl chemistry to form hydrogels and immobilize bioactive factors. Collagen variants retained their triple-helical structure and supported cellular adhesion. Hydrogels were characterized using rheology, and the storage moduli were comparable to fibrillar collagen gels at similar concentrations. Furthermore, the introduced cysteines functioned as anchoring sites, with TGF-ß1-conjugated collagens promoting myofibroblast differentiation. This approach demonstrates the feasibility to produce custom-designed collagens with chemical functionality not available from native sources.

Two-step yielding and directional strain-induced strengthening in dilute colloidal gels.

We investigate the nonlinear rheology of dilute, depletion-induced colloidal gels and report that these systems yield via a two-step process. We propose the two yield points to be associated with interparticle bond rotation and bond breakage, respectively. These distinct yielding mechanisms lead to remarkable creep profiles at intermediate values of the applied stress, highlighted by an anisotropic shear-induced strengthening and flow arrest at very large accumulated strains (γ∼ 80). The possible microstructural origins of this behavior are discussed.

Characteristics of pickering emulsion gels formed by droplet bridging.

We experimentally characterize the microstructure and rheology of a carefully designed mixture of immiscible fluids and near-neutral-wetting colloidal particles. Particle bridging across two fluid interfaces provides a route to highly stable gel-like emulsions at volume fractions of the dispersed phase well below the random close-packing limit for spheres. We investigate the microstructural origins of this behavior by confocal microscopy and reveal a percolating network of colloidal particles that serves as a cohesive scaffold, bridging together droplets of the dispersed phase. Remarkably, the mixture's salient rheological characteristics are governed predominantly by the solids loading and can be tailored irrespective of the droplet volume fraction. The identification of this rheological hallmark could provide a means toward the improved design of modern products that utilize solid-stabilized interfaces.

Dynamics of shear-induced yielding and flow in dilute colloidal gels.

The transient microstructural response of dilute, depletion-induced colloidal gels to shear deformation is probed using a custom-built cone-and-plate shear cell mounted on a fast scanning confocal microscope. We directly unveil an important mode of nonlinear gel yielding, which marks the transition from an immobilized gel network to disconnected flowing clusters at large values of the accumulated strain (γ ~ 0.7). The transition is mediated by a cascade of local rupture events that initiate at the sample's outer edges and propagate inward, resulting in transient dynamic and microstructural heterogeneities in the gel network. Based on the findings, we propose solvent-induced drag as the primary cause of nonlinear rupture, and discuss the coupling between the microstructural evolution and transient rheology in this system.

Hierarchically porous silver monoliths from colloidal bicontinuous interfacially jammed emulsion gels.

Silver monoliths with interconnected hierarchical pore networks and three-dimensional (3D) bicontinuous morphology are synthesized from a colloidal bicontinuous interfacially jammed emulsion gel (bijel) via reduction of silver ions within a nanoporous cross-linked polymer template. The pore sizes may be tuned independently and range from tens of nanometers to over a hundred micrometers. The method is straightforward as well as flexible and can pave the way to a host of hierarchical materials for current technologies.

Relationship between microstructure, dynamics, and rheology in polymer-bridging colloidal gels.

We investigate the link between the microstructure, dynamics, and rheological properties in dense (phi = 0.3) mixtures of charge-stabilized colloidal silica and oppositely charged poly(ethylene imine) polymer in a mixed DMSO/H(2)O solvent. Over a finite range of polymer concentrations, the addition of polymer results in the formation of sample-spanning, self-supporting gel networks. As the polymer concentration is increased, a reentrant rheological transition is observed where the gel's elastic modulus and yield stress initially increase and subsequently drop. The dynamic and microstructural changes associated with this transition are resolved using quantitative confocal microscopy. Within the initial regime, a biphasic system consisting of a mixture of arrested and diffusive particles is observed. We segregate the particles with high accuracy into mobile and arrested populations based on their dynamics. The addition of polymer in this regime systematically decreases the proportion of free particles, until all the particles are arrested. Concurrent with this transition, the elastic modulus and yield stress go through their corresponding maxima. However, over the range of polymer concentrations studied, the reentrant transition to weak gels is not captured by the particle dynamics but is instead accompanied by subtle changes in the microstructure of the arrested phase. We discuss two possible scenarios for this behavior in view of the strength of interparticle bonds.