Stefanie Utech

Microfluidic Generation of Monodisperse, Structurally Homogeneous Alginate Microgels for Cell Encapsulation and 3D Cell Culture.

Monodisperse alginate microgels (10-50 μm) are created via droplet-based microfluidics by a novel crosslinking procedure. Ionic crosslinking of alginate is induced by release of chelated calcium ions. The process separates droplet formation and gelation reaction enabling excellent control over size and homogeneity under mild reaction conditions. Living mesenchymal stem cells are encapsulated and cultured in the generated 3D microenvironments.

A review of hydrogel-based composites for biomedical applications: enhancement of hydrogel properties by addition of rigid inorganic fillers

There is a growing demand for three-dimensional scaffolds for expanding applications in regenerative medicine, tissue engineering, and cell culture techniques. The material requirements for such three-dimensional structures are as diverse as the applications themselves. A wide range of materials have been investigated in the recent decades in order to tackle these requirements and to stimulate the anticipated biological response. Among the most promising class of materials are inorganic/organic hydrogel composites for regenerative medicine. The generation of synergetic effects by hydrogel composite systems enables the design of materials with superior properties including biological performance, stiffness, and degradation behavior in vitro and in vivo. Here, we review the most important organic and inorganic materials used to fabricate hydrogel composites. We highlight the advantages of combining different materials with respect to their use for biofabrication and cell encapsulation as well as their application as injectable materials for tissue enhancement and regeneration.Graphical abstract

Deterministic encapsulation of single cells in thin tunable microgels for niche modelling and therapeutic delivery

Existing techniques to encapsulate cells into microscale hydrogels generally yield high polymer-to-cell ratios and lack control over the hydrogel’s mechanical properties1. Here, we report a microfluidic-based method for encapsulating single cells in a ~6 micron layer of alginate that increases the proportion of cell-containing microgels by 10-fold, with encapsulation efficiencies over 90%. We show that in vitro cell viability was maintained over a three-day period, that the microgels are mechanically tractable, and that for microscale cell assemblages of encapsulated marrow stromal cells cultured in microwells, osteogenic differentiation of encapsulated cells depends on gel stiffness and cell density. We also show that intravenous injection of singly-encapsulated marrow stromal cells into mice delays clearance kinetics and sustains donor-derived soluble factors in vivo. The encapsulation of single cells in tunable hydrogels should find use in a variety of tissue engineering and regenerative medicine applications.

Color from hierarchy: Diverse optical properties of micron-sized spherical colloidal assemblies

Significance Controlling the internal structure over multiple length scales can produce materials with superior properties. This hierarchical design is ubiquitous in nature where materials have evolved to show maximum functionality from a limited choice of available building blocks. Mimicking the emergence of functionality from simple building blocks is a key challenge for man-made materials. Here, we show how a simple confined self-assembly of colloidal particles leads to a complex geometry that displays a surprising variety of optical effects. These effects are a result of the intricate interaction of light with the structural features at different length scales, and the geometry of the self-assembled structure. The results underline the importance of controlling assembly processes over multiple length scales to tailor properties and maximize performance. Materials in nature are characterized by structural order over multiple length scales have evolved for maximum performance and multifunctionality, and are often produced by self-assembly processes. A striking example of this design principle is structural coloration, where interference, diffraction, and absorption effects result in vivid colors. Mimicking this emergence of complex effects from simple building blocks is a key challenge for man-made materials. Here, we show that a simple confined self-assembly process leads to a complex hierarchical geometry that displays a variety of optical effects. Colloidal crystallization in an emulsion droplet creates micron-sized superstructures, termed photonic balls. The curvature imposed by the emulsion droplet leads to frustrated crystallization. We observe spherical colloidal crystals with ordered, crystalline layers and a disordered core. This geometry produces multiple optical effects. The ordered layers give rise to structural color from Bragg diffraction with limited angular dependence and unusual transmission due to the curved nature of the individual crystals. The disordered core contributes nonresonant scattering that induces a macroscopically whitish appearance, which we mitigate by incorporating absorbing gold nanoparticles that suppress scattering and macroscopically purify the color. With increasing size of the constituent colloidal particles, grating diffraction effects dominate, which result from order along the crystal’s curved surface and induce a vivid polychromatic appearance. The control of multiple optical effects induced by the hierarchical morphology in photonic balls paves the way to use them as building blocks for complex optical assemblies—potentially as more efficient mimics of structural color as it occurs in nature.

Tailoring re-entrant geometry in inverse colloidal monolayers to control surface wettability

Controlling the microscopic wetting state of a liquid in contact with a structured surface is the basis for the design of liquid repellent as well as anti-fogging coatings by preventing or enabling a given liquid to infiltrate the surface structures. Similarly, a liquid can be confined to designated surface areas by locally controlling the wetting state, with applications ranging from liquid transport on a surface to creating tailored microenvironments for cell culture or chemical synthesis. The control of the wetting of a low-surface-tension liquid is substantially more difficult compared to water and requires surface structures with overhanging features, known as re-entrant geometries. Here, we use colloidal self-assembly and templating to create two-dimensional nanopore arrays with tailored re-entrant geometry. These pore arrays, termed inverse monolayers, are prepared by backfilling a sacrificial colloidal monolayer with a silica sol–gel precursor material. Varying the precursor concentration enables us to control the degree to which the colloids are embedded into the silica matrix. Upon calcination, nanopores with different opening angles result. The pore opening angle directly correlates with the re-entrant curvature of the surface nanostructures and can be used to control the macroscopic wetting behavior of a liquid sitting on the surface structures. We characterize the wetting of various liquids by static and dynamic contact angles and find correlation between the experimental results and theoretical predictions of the wetting state based on simple geometric considerations. We demonstrate the creation of omniphobic surface coatings that support Cassie–Baxter wetting states for liquids with low surface tensions, including octane (γ = 21.7 mN m−1). We further use photolithography to spatially confine such low-surface-tension liquids to desired areas of the substrate with high accuracy.

Colloidal Polymers with Controlled Sequence and Branching Constructed from Magnetic Field Assembled Nanoparticles

The assembly of nanoparticles into polymer-like architectures is challenging and usually requires highly defined colloidal building blocks. Here, we show that the broad size-distribution of a simple dispersion of magnetic nanocolloids can be exploited to obtain various polymer-like architectures. The particles are assembled under an external magnetic field and permanently linked by thermal sintering. The remarkable variety of polymer-analogue architectures that arises from this simple process ranges from statistical and block copolymer-like sequencing to branched chains and networks. This library of architectures can be realized by controlling the sequencing of the particles and the junction points via a size-dependent self-assembly of the single building blocks.

Hierarchical structural control of visual properties in self-assembled photonic-plasmonic pigments

We present a simple one-pot co-assembly method for the synthesis of hierarchically structured pigment particles consisting of silica inverse-opal bricks that are doped with plasmonic absorbers. We study the interplay between the plasmonic and photonic resonances and their effect on the visual appearance of macroscopic collections of photonic bricks that are distributed in randomized orientations. Manipulating the pore geometry tunes the wavelength- and angle-dependence of the scattering profile, which can be engineered to produce angle-dependent Bragg resonances that can either enhance or contrast with the color produced by the plasmonic absorber. By controlling the overall dimensions of the photonic bricks and their aspect ratios, their preferential alignment can either be encouraged or suppressed. This causes the Bragg resonance to appear either as uniform color travel in the former case or as sparse iridescent sparkle in the latter case. By manipulating the surface chemistry of these photonic bricks, which introduces a fourth length-scale (molecular) of independent tuning into our design, we can further engineer interactions between liquids and the pores. This allows the structural color to be maintained in oil-based formulations, and enables the creation of dynamic liquid-responsive images from the pigment.

Microfluidic Templated Multicompartment Microgels for 3D Encapsulation and Pairing of Single Cells

Controlled encapsulation and pairing of single cells within a confined 3D matrix can enable the replication of the highly ordered cellular structure of human tissues. Microgels with independently controlled compartments that can encapsulate cells within separately confined hydrogel matrices would provide precise control over the route of pairing single cells. Here, a one-step microfluidic method is presented to generate monodisperse multicompartment microgels that can be used as a 3D matrix to pair single cells in a highly biocompatible manner. A method is presented to induce microgels formation on chip, followed by direct extraction of the microgels from oil phase, thereby avoiding prolonged exposure of the microgels to the oil. It is further demonstrated that by entrapping stem cells with niche cells within separate but adjacent compartments of the microgels, it can create complex stem cell niche microenvironments in a controlled manner, which can serve as a useful tool for the study of cell-cell interactions. This microfluidic technique represents a significant step toward high-throughput single cells encapsulation and pairing for the study of intercellular communications at single cell level, which is of significant importance for cell biology, stem cell therapy, and tissue engineering.