Magnetic Click Colloidal Assembly

We introduce a new class of spherical colloids that reversibly self-assemble into well-defined nonlinear structures by virtue of “magnetic patches”. This assembly is driven by tunable magnetostatic binding forces that originate from microscopic permanent magnets embedded underneath the surface of the particles. The resulting clusters form spontaneously in the absence of external magnetizing fields, and their geometry is determined by an interplay between magnetic, steric, and electrostatic interactions. Imposing an external magnetic field enables the clusters to unbind or change their geometry allowing, in principle, the creation of materials with a reconfigurable structural arrangement.

Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform

Important insights into aging have been generated with the genetically tractable and short-lived budding yeast. However, it is still impossible today to continuously track cells by high-resolution microscopic imaging (e.g., fluorescent imaging) throughout their entire lifespan. Instead, the field still needs to rely on a 50-y-old laborious and time-consuming method to assess the lifespan of yeast cells and to isolate differentially aged cells for microscopic snapshots via manual dissection of daughter cells from the larger mother cell. Here, we are unique in achieving continuous and high-resolution microscopic imaging of the entire replicative lifespan of single yeast cells. Our microfluidic dissection platform features an optically prealigned single focal plane and an integrated array of soft elastomer-based micropads, used together to allow for trapping of mother cells, removal of daughter cells, monitoring gradual changes in aging, and unprecedented microscopic imaging of the whole aging process. Using the platform, we found remarkable age-associated changes in phenotypes (e.g., that cells can show strikingly differential cell and vacuole morphologies at the moment of their deaths), indicating substantial heterogeneity in cell aging and death. We envision the microfluidic dissection platform to become a major tool in aging research.

Glass Nanopillar Arrays with Nanogap-Rich Silver Nanoislands for Highly Intense Surface Enhanced Raman Scattering

The enhancement of surface enhanced Raman scattering (SERS) with nanogap-rich silver nanoislands surrounding glass nanopillars at wafer level is reported. High-density hot spots are generated by increasing the number of nanogap-rich nanoislands within a detection volume. The SERS substrate shows a high enhancement factor of over 10⁷ with excellent signal uniformity (∼7.8%) and it enables the label-free detection of aqueous DNA base molecules at nanomolar level.

Biomimetic Droplets for Artificial Engagement of Living Cell Surface Receptors: The Specific Case of the T-Cell

Liquid colloids, in the form of droplets grafted with specific biomolecules, are emerging as potential biomimetic systems. Here we show for the first time the possibility of forming hybrid conjugates between an advanced living cell model, the T-cell of the Jurkat cell line, and a specifically grafted droplet. Using T-cells expressing a fluorescent chimeric protein associated with the TCR/CD3 complex and fluorescent ligand-grafted droplets, we demonstrate formation of an interfacial contact concentrated in linking molecules, the morphology and dynamics of which strongly depend on the targeted receptor. The sequence of events ranges from the initial concentration of molecules following an unbound molecule gradient to active actin-driven spreading and fragmentation of the contact, ending with droplet internalization. We observed synchronized colocalization of receptors and ligands driven by cell dynamics and closely mirrored by the droplet interface. Using intracellular calcium probe Fura-2, we also showed that the cell/droplet interaction can trigger the T-cell signaling cascade. By examining molecular dynamics using FRAP measurements, we observed a nearly frozen cell droplet joining interface. Taken together, our results point to liquid colloids as promising new tools both for probing cell surface interactions and receptor dynamics and for manipulating biological cell functions.

Role of Anisotropy in Electrodynamically Induced Colloidal Aggregates

We investigate the assembly of spherical and anisotropic colloidal particles with the shape of peanuts when subjected to an external alternating electric field. By varying the strength and frequency of the applied field, we observe that both types of particles form clusters at low frequencies due to attractive electrohydrodynamic interactions or disperse into a liquidlike phase at high frequencies due to repulsive dipolar interactions. We characterize the observed structures via pair correlation functions and radius of gyration, and observe a clear difference in the ordering process between the isotropic and anisotropic colloids. Further on, we interpret the cluster formation kinetics in terms of dynamic scaling theory, and observe a faster aggregation of the anisotropic colloids with respect to the isotropic ones.

Selective droplet coalescence using microfluidic systems

We report a microfluidic approach, which allows selective and controlled 1:1, 2:1 or 3:1 droplet fusion. A surfactant-stabilized droplet with an interfacial surfactant coverage, Γ, of >98% will fuse spontaneously with a second droplet when Γ of the latter droplet is <16%. However, when Γ of the second droplet is 66%, the two droplets will not fuse, unless they have previously been brought into contact for critical time τ. Therefore, controlling the number of droplets in contact for time τ allows precise control over the number of fused droplets. We have demonstrated efficient (proportion of droplets coalesced p(c) = 1.0, n > 1000) and selective 1:1, 2:1 or 3:1 droplet fusion (proportion of correctly fused droplets p(s) > 0.99, n > 1000). Coalescence in this regime is induced by hydrodynamic flow causing interface separation and is efficient at different Ca numbers and using different dispersed phases, continuous phases and surfactants. However, when Γ of the second droplet is 96% coalescence is no longer observed. Droplet-based microfluidic systems, in which each droplet functions as an independent microreactor, are proving a promising tool for a wide range of ultrahigh-throughput applications in biology and chemistry. The addition of new reagents to pre-formed droplets is critical to many of these applications and we believe the system described here is a simple and flexible method to do so, as well as a new tool to study interfacial stability phenomena.

Direct observation of columnar liquid crystal droplets

While the columnar liquid crystalline phase in suspensions of plate-like colloids is by now well-established, little is known about the pathway leading to the formation of this highly ordered, self-assembled structure. Here, we present direct observations of the morphology and structure of micrometer-sized droplets of the columnar phase formed in the nematic phase in suspensions of colloidal gibbsite plates. From polarized light microscopy and optical Bragg reflection measurements we deduce that these droplets consist of stacks of platelets in a hexagonal arrangement, forming a disk-shaped droplet. We discuss the relation of this droplet structure to the nucleation pathway of the columnar phase and to the anisotropic nematic–columnar interfacial tension.

Can Janus particles give thermodynamically stable Pickering emulsions?

Emulsions stabilised by solid particles with homogeneous surfaces are thought to be kinetically rather than thermodynamically stable. In the absence of effects due to negative line tension in the contact line around adsorbed particles, the free energy of forming an emulsion droplet coated with a monolayer of adsorbed spherical particles is expected always to be positive, and is dominated by the presence of a fraction of uncovered oil–water interface on the droplet between the particles. It is believed however that particles with well-defined surface areas of different wettability (Janus particles) can be adsorbed considerably more strongly than particles of homogeneous wettability. Here we explore how the greater magnitude of the adsorption free energy of Janus particles can affect the free energy of emulsion formation and show, using a simple approach, that negative free energy changes appear possible. We take into account lateral interactions between adsorbed particles at droplet surfaces arising from electrical, hydration and van der Waals forces.

Renewable Cathode Materials from Biopolymer/Conjugated Polymer Interpenetrating Networks

Renewable and cheap materials in electrodes could meet the need for low-cost, intermittent electrical energy storage in a renewable energy system if sufficient charge density is obtained. Brown liquor, the waste product from paper processing, contains lignin derivatives. Polymer cathodes can be prepared by electrochemical oxidation of pyrrole to polypyrrole in solutions of lignin derivatives. The quinone group in lignin is used for electron and proton storage and exchange during redox cycling, thus combining charge storage in lignin and polypyrrole in an interpenetrating polypyrrole/lignin composite.

“Fluidic batteries” as low-cost sources of power in paper-based microfluidic devices

This communication describes the first paper-based microfluidic device that is capable of generating its own power when a sample is added to the device. The microfluidic device contains galvanic cells (that we term “fluidic batteries”) integrated directly into the microfluidic channels, which provides a direct link between a power source and an analytical function within the device. This capability is demonstrated using an example device that simultaneously powers a surface-mount UV LED and conducts an on-chip fluorescence assay.

Nanoemulsion Composite Microgels for Orthogonal Encapsulation and Release

Crosslinkable nanoemulsions are combined with flow lithography for the synthesis of structured composite microgels with controlled hydrophobic compartments. The microgels are used to demonstrate a number of motifs for controlled encapsulation and release of active compounds, including small molecules, proteins, and nanoparticles, from a single material platform.

Magnetic Transport, Mixing and Release of Cargo with Tailored Nanoliter Droplets

Tailored nanoliter single and double emulsions that can be transported, collected/chained, and purposefully fused using magnetophoretic techniques are demonstrated. We show that such emulsions can be used for mixing, release and reaction of minor amounts of encapsulated cargo with spatial and temporal control, offering promise in applications requiring on-demand cargo release and in droplet-based high-throughput analytics.

Microfabricated Biomaterials for Engineering 3D Tissues

Mimicking natural tissue structure is crucial for engineered tissues with intended applications ranging from regenerative medicine to biorobotics. Native tissues are highly organized at the microscale, thus making these natural characteristics an integral part of creating effective biomimetic tissue structures. There exists a growing appreciation that the incorporation of similar highly organized microscale structures in tissue engineering may yield a remedy for problems ranging from vascularization to cell function control/determination. In this review, we highlight the recent progress in the field of microscale tissue engineering and discuss the use of various biomaterials for generating engineered tissue structures with microscale features. In particular, we will discuss the use of microscale approaches to engineer the architecture of scaffolds, generate artificial vasculature, and control cellular orientation and differentiation. In addition, the emergence of microfabricated tissue units and the modular assembly to emulate hierarchical tissues will be discussed.

Dynamic Electrostatic Lithography: Multiscale On-Demand Patterning on Large-Area Curved Surfaces

Dynamic electrostatic lithography is invented to dynamically generate various patterns on large-area and curved polymer surfaces under the control of electrical voltages. The shape of the pattern can be tuned from random creases and craters to aligned creases, craters and lines, and the size of the pattern from millimeters to sub-micrometers.

Facile Fabrication of Light, Flexible and Multifunctional Graphene Fibers

Macroscopic graphene fibers with strength comparable to carbon nanotube yarns have been fabricated with a facile dimensionally-confined hydrothermal strategy from low-cost, aqueous graphite oxide suspensions, which is shapable, weavable, and has a density of less than 1/7 conventional carbon fibers. In combination with the easy in situ and post-synthesis functionalization, the highly flexible graphene fibers could be woven into smart textiles.

Nanocomposite “Superhighways” by Solution Assembly of Semiconductor Nanostructures with Ligand-Functionalized Conjugated Polymers

Poly(3-hexyl thiophene) containing chain-end thiols or phosphonic acids is crystallized to yield nanowires with the functional groups at the wire edges. CdSe quantum dots and nanorods associate with these fibrils, leading to ‘superhighways’ that consist of alternating parallel lanes of conjugated polymer and CdSe.

Magnetic Electrospun Fibers for Cancer Therapy

Iron oxide nanoparticles (IONPs) for magnetic hyperthermia in cancer treatment have recently gained substantial interest. Unfortunately, the use of free IONPs still faces major challenges such as poor tumor targetability, high variability in the amount of IONPs taken up by the tumor and the IONP leakage from dead cancer cells into the surrounding healthy tissues. The present work reports on electrospun fiber webs, heavily loaded with 50 nm sized IONPs. The high loading capacity of the fibers enables significant heating of the environment upon applying an alternating magnetic field. Furthermore, magnetic fibers can be repeatedly heated without loss of heating capacity or release of IONPs. Upon functionalization of the fiber surface with collagen, human SKOV-3 ovarian cancer cells attached well to the fibers. Applying an alternating magnetic field during 10 minutes to the fiber webs killed all fiber-associated cancer cells. Killing the cells using this method seemed more efficient compared to the use of a warm water bath. As the fiber webs can be i) loaded with a well-controlled amount of IONPs and ii) localized in the body by Magnetic Resonance Imaging, magnetic electrospun fibers may become promising materials for a highly reproducible (repeated) heating of cancer tissues in vivo.

Biomimetic Scaffolds for Tissue Engineering

Biomimetic scaffolds mimic important features of the extracellular matrix (ECM) architecture and can be finely controlled at the nano- or microscale for tissue engineering. Rational design of biomimetic scaffolds is based on consideration of the ECM as a natural scaffold; the ECM provides cells with a variety of physical, chemical, and biological cues that affect cell growth and function. There are a number of approaches available to create 3D biomimetic scaffolds with control over their physical and mechanical properties, cell adhesion, and the temporal and spatial release of growth factors. Here, an overview of some biological features of the natural ECM is presented and a variety of original engineering methods that are currently used to produce synthetic polymer-based scaffolds in pre-fabricated form before implantation, to modify their surfaces with biochemical ligands, to incorporate growth factors, and to control their nano- and microscale geometry to create biomimetic scaffolds are discussed. Finally, in contrast to pre-fabricated scaffolds composed of synthetic polymers, injectable biomimetic scaffolds based on either genetically engineered- or chemically synthesized-peptides of which sequences are derived from the natural ECM are discussed. The presence of defined peptide sequences can trigger in situ hydrogelation via molecular self-assembly and chemical crosslinking. A basic understanding of the entire spectrum of biomimetic scaffolds provides insight into how they can potentially be used in diverse tissue engineering, regenerative medicine, and drug delivery applications.

Direct Gravure Printing of Silicon Nanowires Using Entropic Attraction Forces

The development of a method for large-scale printing of nanowire (NW) arrays onto a desired substrate is crucial for fabricating high-performance NW-based electronics. Here, the alignment of highly ordered and dense silicon (Si) NW arrays at anisotropically etched micro-engraved structures is demonstrated using a simple evaporation process. During evaporation, entropic attraction combined with the internal flow of the NW solution induced the alignment of NWs at the corners of pre-defined structures, and the assembly characteristics of the NWs were highly dependent on the polarity of the NW solutions. After complete evaporation, the aligned NW arrays are subsequently transferred onto a flexible substrate with 95% selectivity using a direct gravure printing technique. As a proof-of-concept, flexible back-gated NW field-effect transistors (FETs) are fabricated. The fabricated FETs have an effective hole mobility of 17.1 cm2·V−1·s−1 and an on/off ratio of ∼2.6 × 105.

Carbon Nanotubes Induce Bone Calcification by Bidirectional Interaction with Osteoblasts

Multi-walled carbon nanotubes (MWCNTs) promote calcification during hydroxyapatite (HA) formation by osteoblasts. Primary cultured osteoblasts are incubated with MWCNTs or carbon black. After culture for 3 weeks, the degree of calcification is very high in the 50 μg mL⁻¹ MWCNT group. Transmission electron microscopy shows needle-like crystals around the MWCNTs, and diffraction patterns reveal that the peak of the crystals almost coincides with the known peak of HA.

DFT-Chemical Pressure Analysis: Visualizing the Role of Atomic Size in Shaping the Structures of Inorganic Materials

Atomic size effects have long played a role in our empirical understanding of inorganic crystal structures. At the level of electronic structure calculations, however, the contribution of atomic size remains difficult to analyze, both alone and relative to other influences. In this paper, we extend the concepts outlined in a recent communication to develop a theoretical method for revealing the impact of the space requirements of atoms: the density functional theory-chemical pressure (DFT-CP) analysis. The influence of atomic size is most pronounced when the optimization of bonding contacts is impeded by steric repulsion at other contacts, resulting in nonideal interatomic distances. Such contacts are associated with chemical pressures (CPs) acting upon the atoms involved. The DFT-CP analysis allows for the calculation and interpretation of the CP distributions within crystal structures using DFT results. The method is demonstrated using the stability of the Ca₂Ag₇ structure over the simpler CaCu₅-type alternative adopted by its Sr-analogue, SrAg₅. A hypothetical CaCu₅-type CaAg₅ phase is found to exhibit large negative pressures on each Ca atom, which are concentrated in two symmetry-related interstitial spaces on opposite sides of the Ca nucleus. In moving to the Ca₂Ag₇ structure, relief comes to each Ca atom as a defect plane is introduced into one of these two negative-pressure regions, breaking the symmetry equivalence of the two sides and yielding a more compact Ca coordination environment. These results illustrate how the DFT-CP analysis can visually and intuitively portray how atomic size interacts with electronics in determining structure, and bridge theoretical and experimental approaches toward understanding the structural chemistry of inorganic materials.

Catalytic Janus Motors on Microfluidic Chip: Deterministic Motion for Targeted Cargo Delivery

We fabricated self-powered colloidal Janus motors combining catalytic and magnetic cap structures, and demonstrated their performance for manipulation (uploading, transportation, delivery) and sorting of microobjects on microfluidic chips. The specific magnetic properties of the Janus motors are provided by ultrathin multilayer films that are designed to align the magnetic moment along the main symmetry axis of the cap. This unique property allows a deterministic motion of the Janus particles at a large scale when guided in an external magnetic field. The observed directional control of the motion combined with extensive functionality of the colloidal Janus motors conceptually opens a straightforward route for targeted delivery of species, which are relevant in the field of chemistry, biology, and medicine.

Controlled Synthesis of Cell-Laden Microgels by Radical-Free Gelation in Droplet Microfluidics

Micrometer-sized hydrogel particles that contain living cells can be fabricated with exquisite control through the use of droplet-based microfluidics and bioinert polymers such as polyethyleneglycol (PEG) and hyperbranched polyglycerol (hPG). However, in existing techniques, the microgel gelation is often achieved through harmful reactions with free radicals. This is detrimental for the viability of the encapsulated cells. To overcome this limitation, we present a technique that combines droplet microfluidic templating with bio-orthogonal thiol–ene click reactions to fabricate monodisperse, cell-laden microgel particles. The gelation of these microgels is achieved via the nucleophilic Michael addition of dithiolated PEG macro-cross-linkers to acrylated hPG building blocks and does not require any initiator. We systematically vary the microgel properties through the use of PEG linkers with different molecular weights along with different concentrations of macromonomers to investigate the influence of these parameters on the viability and proliferation of encapsulated yeast cells. We also demonstrate the encapsulation of mammalian cells including fibroblasts and lymphoblasts.

Tuning Multiphase Amphiphilic Rods to Direct Self-Assembly

New methods to direct the self-assembly of particles are highly sought after for multiple applications, including photonics, electronics, and drug delivery. Most techniques, however, are limited to chemical patterning on spherical particles, limiting the range of possible structures. We developed a lithographic technique for fabrication of chemically anisotropic rod-like particles in which we can specify both the size and shape of particles and implement multiple diverse materials to control interfacial interactions. Multiphase rod-like particles, including amphiphilic diblock, triblock, and multiblock were fabricated in the same template mold having a tunable hydrophilic/hydrophobic ratio. Self-assembly of diblock or triblock rods at a water/oil interface led to the formation of bilayer or ribbon-like structures.

Capillary bond between rod-like particles and the micromechanics of particle-laden interfaces

Rod-like microparticles assemble by capillarity at fluid interfaces to make distinctively different microstructures depending on the details of the particle shape. Ellipsoidal particles assemble in side-to-side orientations to form flexible chains, whereas cylinders assemble end-to-end to form rigid chains. To understand these differences, we simulate the near-field capillary interactions between pairs of rod-like particles subject to bond-stretching and bond-bending deformations. By comparing ellipsoids, cylinders, and cylinders with smooth edges, we show that geometric details dramatically affect the magnitude and shape of the capillary energy landscape. We relate this energy landscape to the mechanics of the chains, predicting the flexural rigidity for chains of ellipsoids, and a complex, non-elastic response for chains of cylinders. These results have implications in the design of particle laden interfaces for emulsion stabilization and encapsulation, and for oriented assembly of anisotropic materials.

A three-dimensional polymer scaffolding material exhibiting a zero Poisson's ratio

Poisson's ratio describes the degree to which a material contracts (expands) transversally when axially strained. A material with a zero Poisson's ratio does not transversally deform in response to an axial strain (stretching). In tissue engineering applications, scaffolding having a zero Poisson's ratio (ZPR) may be more suitable for emulating the behavior of native tissues and accommodating and transmitting forces to the host tissue site during wound healing (or tissue regrowth). For example, scaffolding with a zero Poisson's ratio may be beneficial in the engineering of cartilage, ligament, corneal, and brain tissues, which are known to possess Poisson's ratios of nearly zero. Here, we report a 3D biomaterial constructed from polyethylene glycol (PEG) exhibiting in-plane Poisson's ratios of zero for large values of axial strain. We use digital micro-mirror device projection printing (DMD-PP) to create single- and double-layer scaffolds composed of semi-re-entrant pores whose arrangement and deformation mechanisms contribute to the zero Poisson's ratio. Strain experiments prove the zero Poisson's behavior of the scaffolds and that the addition of layers does not change the Poisson's ratio. Human mesenchymal stem cells (hMSCs) cultured on biomaterials with zero Poisson's ratio demonstrate the feasibility of utilizing these novel materials for biological applications which require little to no transverse deformations resulting from axial strains. Techniques used in this work allow Poisson's ratio to be both scale-independent and independent of the choice of strut material for strains in the elastic regime, and therefore ZPR behavior can be imparted to a variety of photocurable biomaterials.

Sonic Hedgehog-activated engineered blood vessels enhance bone tissue formation

Large bone defects naturally regenerate via a highly vascularized tissue which progressively remodels into cartilage and bone. Current approaches in bone tissue engineering are restricted by delayed vascularization and fail to recapitulate this stepwise differentiation toward bone tissue. Here, we use the morphogen Sonic Hedgehog (Shh) to induce the in vitro organization of an endothelial capillary network in an artificial tissue. We show that endogenous Hedgehog activity regulates angiogenic genes and the formation of vascular lumens. Exogenous Shh further induces the in vitro development of the vasculature (vascular lumen formation, size, distribution). Upon implantation, the in vitro development of the vasculature improves the in vivo perfusion of the artificial tissue and is necessary to contribute to, and enhance, the formation of de novo mature bone tissue. Similar to the regenerating callus, the artificial tissue undergoes intramembranous and endochondral ossification and forms a trabecular-like bone organ including bone-marrow-like cavities. These findings open the door for new strategies to treat large bone defects by closely mimicking natural endochondral bone repair.

From soft to hard: the generation of functional and complex colloidal monolayers for nanolithography

Take polymer colloids—simple to make and ubiquitously available—let them self-assemble into a monolayer and you have, readily engineered, a sophisticated mask to create highly symmetric surface patterns with nanometre precision. Thirty years after its invention, this process, commonly referred to as colloidal lithography, is far from being old news and an ever-increasing range of scientists continues to use their creativity to come up with increasingly more complex surface patterns. As intriguing this technique is, the devil is in the details and it is far from trivial to achieve high order in a colloidal monolayer. This article reviews available crystallization techniques and discusses their scope and limitations in order to provide just the right method for your next experiment.

Simple Localization of Nanofiber Scaffolds via SU-8 Photoresist and Their Use for Parallel 3D Cellular Assays

A simple, new approach to localizing electrospun nanofiber scaffolds simply by direct writing of SU-8 photoresist followed by UV polymerization is presented. This method allows 3D cell culture arrays to be produced (see figure) and it can be integrated with microfluidic devices easily to enable low-cost high-throughput cellular assays within an addressable 3D environment, which is attractive for use in drug screening, stem cell research, tissue engineering, and regenerative medicine.

Copper ion liquid-like thermoelectrics

Advanced thermoelectric technology offers a potential for converting waste industrial heat into useful electricity, and an emission-free method for solid state cooling^{1, 2}. Worldwide efforts to find materials with thermoelectric figure of merit, zT values significantly above unity, are frequently focused on crystalline semiconductors with low thermal conductivity². Here we report on Cu_2−xSe, which reaches a zT of 1.5 at 1,000 K, among the highest values for any bulk materials. Whereas the Se atoms in Cu_2−xSe form a rigid face-centred cubic lattice, providing a crystalline pathway for semiconducting electrons (or more precisely holes), the copper ions are highly disordered around the Se sublattice and are superionic with liquid-like mobility. This extraordinary ‘liquid-like’ behaviour of copper ions around a crystalline sublattice of Se in Cu_2−xSe results in an intrinsically very low lattice thermal conductivity which enables high zT in this otherwise simple semiconductor. This unusual combination of properties leads to an ideal thermoelectric material. The results indicate a new strategy and direction for high-efficiency thermoelectric materials by exploring systems where there exists a crystalline sublattice for electronic conduction surrounded by liquid-like ions.

Controlling Liquid Drops with Texture Ratchets

Controlled vibration selectively propels multiple microliter-sized drops along microstructured tracks, leading to simple microfluidic systems that rectify oscillations of the three-phase contact line into asymmetric pinning forces that propel each drop in the direction of higher pinning.

Cardiac tissue engineering using tissue printing technology and human cardiac progenitor cells

Tissue engineering is emerging as a potential therapeutic approach to overcome limitations of cell therapy, like cell retention and survival, as well as to mechanically support the ventricular wall and thereby prevent dilation. Tissue printing technology (TP) offers the possibility to deliver, in a defined and organized manner, scaffolding materials and living cells. The aim of our study was to evaluate the combination of TP, human cardiac-derived cardiomyocyte progenitor cells (hCMPCs) and biomaterials to obtain a construct with cardiogenic potential for in vitro use or in vivo application. With this approach, we were able to generate an in vitro tissue with homogenous distribution of cells in the scaffold. Cell viability was determined after printing and showed that 92% and 89% of cells were viable at 1 and 7 days of culturing, respectively. Moreover, we demonstrated that printed hCMPCs retained their commitment for the cardiac lineage. In particular, we showed that 3D culture enhanced gene expression of the early cardiac transcription factors Nkx2.5, Gata-4 and Mef-2c as well as the sarcomeric protein TroponinT. Printed cells were also able to migrate from the alginate matrix and colonize a matrigel layer, thereby forming tubular-like structures. This indicated that printing can be used for defined cell delivery, while retaining functional properties.

Biomimetic cilia arrays generate simultaneous pumping and mixing regimes



Living systems employ cilia to control and to sense the flow of fluids for many purposes, such as pumping, locomotion, feeding, and tissue morphogenesis. Beyond their use in biology, functional arrays of artificial cilia have been envisaged as a potential biomimetic strategy for inducing fluid flow and mixing in lab-on-a-chip devices. Here we report on fluid transport produced by magnetically actuated arrays of biomimetic cilia whose size approaches that of their biological counterparts, a scale at which advection and diffusion compete to determine mass transport. Our biomimetic cilia recreate the beat shape of embryonic nodal cilia, simultaneously generating two sharply segregated regimes of fluid flow: Above the cilia tips their motion causes directed, long-range fluid transport, whereas below the tips we show that the cilia beat generates an enhanced diffusivity capable of producing increased mixing rates. These two distinct types of flow occur simultaneously and are separated in space by less than 5 μm, approximately 20% of the biomimetic cilium length. While this suggests that our system may have applications as a versatile microfluidics device, we also focus on the biological implications of our findings. Our statistical analysis of particle transport identifying an enhanced diffusion regime provides novel evidence for the existence of mixing in ciliated systems, and we demonstrate that the directed transport regime is Poiseuille–Couette flow, the first analytical model consistent with biological measurements of fluid flow in the embryonic node.

Designing Responsive Buckled Surfaces by Halftone Gel Lithography

Self-actuating materials capable of transforming between three-dimensional shapes have applications in areas as diverse as biomedicine, robotics, and tunable micro-optics. We introduce a method of photopatterning polymer films that yields temperature-responsive gel sheets that can transform between a flat state and a prescribed three-dimensional shape. Our approach is based on poly(N-isopropylacrylamide) copolymers containing pendent benzophenone units that allow cross-linking to be tuned by irradiation dose. We describe a simple method of halftone gel lithography using only two photomasks, wherein highly cross-linked dots embedded in a lightly cross-linked matrix provide access to nearly continuous, and fully two-dimensional, patterns of swelling. This method is used to fabricate surfaces with constant Gaussian curvature (spherical caps, saddles, and cones) or zero mean curvature (Enneper’s surfaces), as well as more complex and nearly closed shapes.