Topography-Guided Control of Local Migratory Behaviors and Protein Expression of Cancer Cells.

In vivo cancer cell migration and invasion are directed by biophysical guidance mechanisms such as pre-existing microtracks and basement membrane extracellular matrices. Here, this paper reports the correlation of the local migratory behavior of cancer cells and the biochemical signal expression using the topography that can guide or inhibit cell behaviors. To this end, the local apparent migration and the protein expression level are investigated with respect to the topographical feature size (flat, nanoline, and microline) and orientation (microline, microconcentric, and microradial) with the collectively migrating (A431) and individually migrating (MDA-MB-231 and U-87-MG) cancer cells.

3D tissue formation by stacking detachable cell sheets formed on nanofiber mesh.

We present a novel approach for assembling 3D tissue by layer-by-layer stacking of cell sheets formed on aligned nanofiber mesh. A rigid frame was used to repeatedly collect aligned electrospun PCL (polycaprolactone) nanofiber to form a mesh structure with average distance between fibers 6.4 µm.

Artificial Slanted Nanocilia Array as a Mechanotransducer for Controlling Cell Polarity.

We present a method to induce cell directional behavior using slanted nanocilia arrays. NIH-3T3 fibroblasts demonstrated bidirectional polarization in a rectangular arrangement on vertical nanocilia arrays and exhibited a transition from a bidirectional to a unidirectional polarization pattern when the angle of the nanocilia was decreased from 90° to 30°. The slanted nanocilia guided and facilitated spreading by allowing the cells to contact the sidewalls of the nanocilia, and the directional migration of the cells opposed the direction of the slant due to the anisotropic bending stiffness of the slanted nanocilia.

Nonlinear Frameworks for Reversible and Pluripotent Wetting on Topographic Surfaces.

Soft, ultrathin frameworks nonlinearly organized in tandem are presented to realize both reversible and pluripotent wetting on topographic surfaces. A design rule is introduced by establishing and proving the theoretical model upon hierarchical textures. Nonlinear frameworks can be conformally and reversibly wet upon complex topography in nature, thereby overcoming the wetting problems in previous conventional solid systems.

Directed migration of cancer cells guided by the graded texture of the underlying matrix.

Living cells and the extracellular matrix (ECM) can exhibit complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration-which we term 'topotaxis'-guided by the gradient of the nanoscale topographic features in the cells' ECM environment. We show that the direction of topotaxis is reflective of the effective cell stiffness, and that it depends on the balance of the ECM-triggered signalling pathways PI(3)K-Akt and ROCK-MLCK.

Creation of a Hybrid Scaffold with Dual Configuration of Aligned and Random Electrospun Fibers.

A novel hybrid construct was developed by combining aligned fibers (AFs) and random fibers (RFs) to form a scaffolding system. Homogeneous fiber-based structures were fabricated by electrospinning, which produced both random and aligned fiber mats depending on the collection method. The upper part of the scaffold contained an AF layer, which possessed a well-organized configuration that provided uniaxial topographic guidance.

Remote Manipulation of Droplets on a Flexible Magnetically Responsive Film.

The manipulation of droplets is used in a wide range of applications, from lab-on-a-chip devices to bioinspired functional surfaces. Although a variety of droplet manipulation techniques have been proposed, active, fast and reversible manipulation of pure discrete droplets remains elusive due to the technical limitations of previous techniques. Here, we describe a novel technique that enables active, fast, precise and reversible control over the position and motion of a pure discrete droplet with only a permanent magnet by utilizing a magnetically responsive flexible film possessing actuating hierarchical pillars on the surface.

Multiplex lithography for multilevel multiscale architectures and its application to polymer electrolyte membrane fuel cell.

The production of multiscale architectures is of significant interest in materials science, and the integration of those structures could provide a breakthrough for various applications. Here we report a simple yet versatile strategy that allows for the LEGO-like integrations of microscale membranes by quantitatively controlling the oxygen inhibition effects of ultraviolet-curable materials, leading to multilevel multiscale architectures. The spatial control of oxygen concentration induces different curing contrasts in a resin allowing the selective imprinting and bonding at different sides of a membrane, which enables LEGO-like integration together with the multiscale pattern formation.

Robust microzip fastener: repeatable interlocking using polymeric rectangular parallelepiped arrays.

We report a highly repeatable and robust microzip fastener based on the van der Waals force-assisted interlocking between rectangular parallelepiped arrays. To investigate zipperlike interlocking behaviors, various line arrays were fabricated with three different spacing ratios (1, 3, and 5 of 800 nm in width) and width of parallelepipeds (400 nm, 800 nm, and 5 μm with the spacing ratio of 1). In addition, the different rigidity of line arrays was inspected for a repeatable microzip fastener.

Ultrasensitive mechanical crack-based sensor inspired by the spider sensory system.

Recently developed flexible mechanosensors based on inorganic silicon, organic semiconductors, carbon nanotubes, graphene platelets, pressure-sensitive rubber and self-powered devices are highly sensitive and can be applied to human skin. However, the development of a multifunctional sensor satisfying the requirements of ultrahigh mechanosensitivity, flexibility and durability remains a challenge. In nature, spiders sense extremely small variations in mechanical stress using crack-shaped slit organs near their leg joints.

Microfluidic platforms with monolithically integrated hierarchical apertures for the facile and rapid formation of cargo-carrying vesicles.

We fabricated a simple yet robust microfluidic platform with monolithically integrated hierarchical apertures. This platform showed efficient diffusive mixing of the introduced lipids through approximately 8000 divisions with tiny pores (~5 μm in diameter), resulting in massive, real-time production of various cargo-carrying particles via multi-hydrodynamic focusing.

Repetitive cleavage of elastomeric membrane via controlled interfacial fracture.

Here, we report a method of fabricating thin layer of polydimethylsiloxane (PDMS), with a thickness in the range of 60-80 nm, which can be repeatedly generated (more than 10 times) from the same block of PDMS via controlled interfacial fracture. The thin layers can be transferred to various substrates by peeling off from the bulk PDMS. The cleavage is attributed to the built-in stress at the fracture interface due to plasma treatment, resulting in the repetitive formation of the thin membranes, with no residue from processing, and with a surface roughness of ∼5 nm.

Janus-compartmental alginate microbeads having polydiacetylene liposomes and magnetic nanoparticles for visual lead(II) detection.

Janus-compartmental alginate microbeads having two divided phases of sensory polydiacetylene (PDA) liposomes and magnetic nanoparticles were fabricated for facile sensory applications. The sensory liposomes are composed of PDA for label-free signal generation and 1,2-dipalmitoyl-sn-glycero-3-galloyl (DPGG) lipids whose galloyl headgroup has specific interactions with lead(II). The second phase having magnetic nanoparticles is designed for convenient handling of the microbeads, such as washing, solvent exchange, stirring, and detection, by applying magnetic field.

Hierarchical multilayer assembly of an ordered nanofibrous scaffold via thermal fusion bonding.

A major challenge in muscle tissue engineering is mimicking the ordered nanostructure of native collagen fibrils in muscles. Electrospun nanofiber constructs have been proposed as promising candidate alternatives to natural extracellular matrix. Here, we introduce a novel method to fabricate a two-dimension (2D) sheet-type and three-dimensionally integrated nanofibrous scaffolds by combining electrospinning and rapid prototyping.

T cells sense biophysical cues using lamellipodia and filopodia to optimize intraluminal path finding.

Intraluminal crawling is considered to be important for extravasation of leukocytes in blood vessels, but biochemical/biophysical cues guiding the crawling of leukocytes have not been clearly understood. Here we provide evidence that T cells sense the topography of luminal surfaces and the nuclei of endothelial cells (ECs) using lamellipodia and filopodia, respectively, to optimize path finding during intraluminal crawling. Well-aligned EC layers or replicas of EC layers, which exhibit topography similar to that of EC layers, were fabricated, and flow was applied either parallel or perpendicular to the orientation of EC alignment.

Replication of flexible polymer membranes with geometry-controllable nano-apertures via a hierarchical mould-based dewetting.

Membranes with nano-apertures are versatile templates that possess a wide range of electronic, optical and biomedical applications. However, such membranes have been limited to silicon-based inorganic materials to utilize standard semiconductor processes. Here we report a new type of flexible and free-standing polymeric membrane with nano-apertures by exploiting high-wettability difference and geometrical reinforcement via multiscale, multilevel architecture.

Spatial control of adult stem cell fate using nanotopographic cues.

Adult stem cells hold great promise as a source of diverse terminally differentiated cell types for tissue engineering applications. However, due to the complexity of chemical and mechanical cues specifying differentiation outcomes, development of arbitrarily complex geometric and structural arrangements of cells, adopting multiple fates from the same initial stem cell population, has been difficult. Here, we show that the topography of the cell adhesion substratum can be an instructive cue to adult stem cells and topographical variations can strongly bias the differentiation outcome of the cells towards adipocyte or osteocyte fates.

25th anniversary article: scalable multiscale patterned structures inspired by nature: the role of hierarchy.

Multiscale, hierarchically patterned surfaces, such as lotus leaves, butterfly wings, adhesion pads of gecko lizards are abundantly found in nature, where microstructures are usually used to strengthen the mechanical stability while nanostructures offer the main functionality, i.e., wettability, structural color, or dry adhesion.

Designing nanotopographical density of extracellular matrix for controlled morphology and function of human mesenchymal stem cells.

Inspired by ultrastructural analysis of ex vivo human tissues as well as the physiological importance of structural density, we fabricated nanogrooves with 1:1, 1:3, and 1:5 spacing ratio (width:spacing, width = 550 nm). In response to the nanotopographical density, the adhesion, migration, and differentiation of human mesenchymal stem cells (hMSCs) were sensitively controlled, but the proliferation showed no significant difference. In particular, the osteo- or neurogenesis of hMSCs were enhanced at the 1:3 spacing ratio rather than 1:1 or 1:5 spacing ratio, implying an existence of potentially optimized nanotopographical density for stem cell function.

Nanopatterned muscle cell patches for enhanced myogenesis and dystrophin expression in a mouse model of muscular dystrophy.

Skeletal muscle is a highly organized tissue in which the extracellular matrix (ECM) is composed of highly-aligned cables of collagen with nanoscale feature sizes, and provides structural and functional support to muscle fibers. As such, the transplantation of disorganized tissues or the direct injection of cells into muscles for regenerative therapy often results in suboptimal functional improvement due to a failure to integrate with native tissue properly. Here, we present a simple method in which biodegradable, biomimetic substrates with precisely controlled nanotopography were fabricated using solvent-assisted capillary force lithography (CFL) and were able to induce the proper development and differentiation of primary mononucleated cells to form mature muscle patches.

Instantly switchable adhesion of bridged fibrillar adhesive via gecko-inspired detachment mechanism and its application to a transportation system.

Inspired by the exceptional climbing ability of gecko lizards, artificial fibrillar adhesives have been extensively studied over the last decade both experimentally and theoretically. Therefore, a new leap towards practical uses beyond the academic horizon is timely and highly anticipated. To this end, we present a fibrillar adhesive in the form of bridged micropillars and its application to a transportation system with the detachment mechanism inspired by the climbing behaviour of gecko lizards.

Stimuli-responsive hydrogel patterns for smart microfluidics and microarrays.

In this review, we highlight the properties, functions and applications of stimuli-responsive hydrogel patterns in bioanalytical applications. Stimuli-responsive hydrogel patterns can be realized by well-established micro- and nanofabrication technologies such as photolithography and micromolding, and are currently adopted as active components for manipulation of flow and biosamples in microchannel and microarray systems. We overview the properties of stimuli-responsive hydrogel materials and their fabrication methods along with some representative examples in microfluidics and microarrays.

Hybrid microfabrication of nanofiber-based sheets and rods for tissue engineering applications.

Electrospun nanofibers have been developed into a variety of forms for tissue engineering scaffolds to regulate the cellular functions guided by nanotopographical cues. Here, we have successfully fabricated nanofiber-based scaffold complexes of rod and sheet type by combining the three microfabrication techniques of electrospinning, spin coating, and polymer melt deposition. It was demonstrated that this hybrid fabrication could produce uniaxially aligned nanofiber scaffolds supported by a thin film, allowing for a mechanically enforced substrate for cell culture as well as facile scaffold manipulation.

Directional oil sliding surfaces with hierarchical anisotropic groove microstructures.

A robust directional oil sliding surface is presented by utilizing re-entrant micro-groove arrays inspired from the microgrooves of rice leaf. The overhang micro-groove arrays are shown to provide two primary goals of "omniphobicty" and "anisotropic sliding" with DI water (γlv = 72.1 mN/m) as well as mineral oil (γlv = 28 mN/m) and conventional photoresist.

Synergistic effects of nanotopography and co-culture with endothelial cells on osteogenesis of mesenchymal stem cells.

Inspired by the aligned nanostructures and co-existence of vascular cells and stem cells in human cancellous bone, we quantitatively investigated the relative contributions of nanotopography and co-culture with human umbilical endothelial cells (HUVECs) to the osteogenesis of human mesenchymal stem cells (hMSCs). Although both nanotopography and co-culture independently enhanced the osteogenesis of hMSCs, osteogenesis was further enhanced by the two factors in combination, indicating the importance of synergistic cues in stem cell engineering. Interestingly, nanotopography provided a larger relative contribution to the osteogenesis of hMSCs than did co-culture with HUVECs.