Kahp Y. Suh

Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs

Heart tissue possesses complex structural organization on multiple scales, from macro- to nano-, but nanoscale control of cardiac function has not been extensively analyzed. Inspired by ultrastructural analysis of the native tissue, we constructed a scalable, nanotopographically controlled model of myocardium mimicking the in vivo ventricular organization. Guided by nanoscale mechanical cues provided by the underlying hydrogel, the tissue constructs displayed anisotropic action potential propagation and contractility characteristic of the native tissue. Surprisingly, cell geometry, action potential conduction velocity, and the expression of a cell–cell coupling protein were exquisitely sensitive to differences in the substratum nanoscale features of the surrounding extracellular matrix. We propose that controlling cell–material interactions on the nanoscale can stipulate structure and function on the tissue level and yield novel insights into in vivo tissue physiology, while providing materials for tissue repair.

A nontransferring dry adhesive with hierarchical polymer nanohairs

We present a simple yet robust method for fabricating angled, hierarchically patterned high-aspect-ratio polymer nanohairs to generate directionally sensitive dry adhesives. The slanted polymeric nanostructures were molded from an etched polySi substrate containing slanted nanoholes. An angled etching technique was developed to fabricate slanted nanoholes with flat tips by inserting an etch-stop layer of silicon dioxide. This unique etching method was equipped with a Faraday cage system to control the ion-incident angles in the conventional plasma etching system. The polymeric nanohairs were fabricated with tailored leaning angles, sizes, tip shapes, and hierarchical structures. As a result of controlled leaning angle and bulged flat top of the nanohairs, the replicated, slanted nanohairs showed excellent directional adhesion, exhibiting strong shear attachment (≈26 N/cm2 in maximum) in the angled direction and easy detachment (≈2.2 N/cm2) in the opposite direction, with a hysteresis value of ≈10. In addition to single scale nanohairs, monolithic, micro-nanoscale combined hierarchical hairs were also fabricated by using a 2-step UV-assisted molding technique. These hierarchical nanoscale patterns maintained their adhesive force even on a rough surface (roughness <20 μm) because of an increase in the contact area by the enhanced height of hierarchy, whereas simple nanohairs lost their adhesion strength. To demonstrate the potential applications of the adhesive patch, the dry adhesive was used to transport a large-area glass (47.5 × 37.5 cm2, second-generation TFT-LCD glass), which could replace the current electrostatic transport/holding system with further optimization.

Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/groove pattern arrays

Human embryonic stem cells (hESCs) are pluripotent cells that have the potential to be used for tissue engineering and regenerative medicine. Repairing nerve injury by differentiating hESCs into a neuronal lineage is one important application of hESCs. Biochemical and biological agents are widely used to induce hESC differentiation. However, it would be better if we could induce differentiation of hESCs without such agents because these factors are expensive and it is difficult to control the optimal concentrations for efficient differentiation with reduced side effects. Moreover, the mechanism of differentiation induced by these factors is still not fully understood. In this study, we present evidence that nanoscale ridge/groove pattern arrays alone can effectively and rapidly induce the differentiation of hESCs into a neuronal lineage without the use any differentiation-inducing agents. Using UV-assisted capillary force lithography, we constructed nanoscale ridge/groove pattern arrays with a dimension and alignment that were finely controlled over a large area. Human embryonic stem cells seeded onto the 350-nm ridge/groove pattern arrays differentiated into neuronal lineage after five days, in the absence differentiation-inducing agents. This nanoscale technique could be used for a new neuronal differentiation protocol of hESCs and may also be useful for nanostructured scaffolding for nerve injury repair.

Nanotopography-guided tissue engineering and regenerative medicine ☆

Human tissues are intricate ensembles of multiple cell types embedded in complex and well-defined structures of the extracellular matrix (ECM). The organization of ECM is frequently hierarchical from nano to macro, with many proteins forming large scale structures with feature sizes up to several hundred microns. Inspired from these natural designs of ECM, nanotopography-guided approaches have been increasingly investigated for the last several decades. Results demonstrate that the nanotopography itself can activate tissue-specific function in vitro as well as promote tissue regeneration in vivo upon transplantation. In this review, we provide an extensive analysis of recent efforts to mimic functional nanostructures in vitro for improved tissue engineering and regeneration of injured and damaged tissues. We first characterize the role of various nanostructures in human tissues with respect to each tissue-specific function. Then, we describe various fabrication methods in terms of patterning principles and material characteristics. Finally, we summarize the applications of nanotopography to various tissues, which are classified into four types depending on their functions: protective, mechano-sensitive, electro-active, and shear stress-sensitive tissues. Some limitations and future challenges are briefly discussed at the end.

Rational design and enhanced biocompatibility of a dry adhesive medical skin patch.

This work was supported by National Research Foundation of Korea (NRF) grant (No. 20110017530), WCU (World Class University) program (R31-2008-000-10083-0) on multiscale mechanical design, and Basic Science Research Program (2010-0027955) funded by the Ministry of Education, Science, and Technology (MEST). This work was supported in part by the Award No KUK-F1-037-02, made by King Abdullah University of Science and Technology (KAUST) and Institute of Advanced Machinery and Design (IAMD) of Seoul National University.

Cell research with physically modified microfluidic channels: A review

An overview of the use of physically modified microfluidic channels towards cell research is presented. The physical modification can be realized either by combining embedded physical micro/nanostructures or a topographically patterned substrate at the micro- or nanoscale inside a channel. After a brief description of the background and the importance of the physically modified microfluidic system, various fabrication methods are described based on the materials and geometries of physical structures and channels. Of many operational principles for microfluidics (electrical, magnetic, optical, mechanical, and so on), this review primarily focuses on mechanical operation principles aided by structural modification of the channels. The mechanical forces are classified into (i) hydrodynamic, (ii) gravitational, (iii) capillary, (iv) wetting, and (v) adhesion forces. Throughout this review, we will specify examples where necessary and provide trends and future directions in the field.

Fabrication of three-dimensional microstructures by soft molding

We have developed soft molding as a method for meso-scale-area fabrication of three-dimensional structures. The soft molding, which is a form of soft lithography, involves placing an elastomeric mold on the surface of a spin-coated polymer film with a slight pressure (<1 N/cm2), allowing the mold to absorb solvent, releasing the pressure, and then letting the mold and the substrate remain undisturbed for a period of time. The three-dimensional structure thus formed is robust in that the pattern fidelity is preserved without any distortion or defects. For the soft molding to be successful, the rate of solvent absorption by the mold should be larger than the rate of solvent evaporation. The method is demonstrated with several three-dimensional structures.

Stretchable, Adhesion-Tunable Dry Adhesive by Surface Wrinkling

We introduce a simple yet robust method of fabricating a stretchable, adhesion-tunable dry adhesive by combining replica molding and surface wrinkling. By utilizing a thin, wrinkled polydimethyl siloxane (PDMS) sheet with a thickness of 1 mm with built-in micropillars, active, dynamic control of normal and shear adhesion was achieved. Relatively strong normal (approximately 10.8 N/cm(2)) and shear adhesion (approximately 14.7 N/cm(2)) forces could be obtained for a fully extended (strained) PDMS sheet (prestrain of approximately 3%), whereas the forces could be rapidly reduced to nearly zero once the prestrain was released (prestrain of approximately 0.5%). Moreover, durability tests demonstrated that the adhesion strength in both the normal and shear directions was maintained over more than 100 cycles of attachment and detachment.

Nanopatterned cardiac cell patches promote stem cell niche formation and myocardial regeneration.

Stem cell-based methods for myocardial regeneration suffer from considerable cell attrition. Artificial matrices reproducing mechanical and structural properties of the native tissue may facilitate survival, retention and functional integration of adult stem or progenitor cells, by conditioning the cells prior to, and during, transplantation. Here we combined autologous cardiosphere-derived cells (CDCs) with nanotopographically defined hydrogels mimicking the native myocardial matrix, to form in vitro cardiac stem cell niches, and control cell function and fate. These platforms were used to produce cardiac patches that could be transplanted at the site of infarct. In culture, highly anisotropic, but not more randomized nanotopographic, control augmented cell adhesion, migration, and proliferation. It also dramatically enhanced early, and, in the presence of mature cardiomyocytes, late cardiomyogenesis. Nanotopography sensing and transcriptional response was mediated via p190RhoGAP. In a rat infarction model, engraftment of nanofabricated scaffolds with CDCs enhanced retention and growth of transplanted cells, and their integration with the host tissue. The infarcted ventricle wall increased in thickness, with higher cell viability and better collagen organization. These results suggest that nanostructured polymeric materials that closely mimic the extracellular matrix structure on which cardiac cells reside in vivo can be both very effective tools in investigating the mechanisms of cardiac differentiation and the basis for cardiac tissue engineering, thus facilitating stem cell-based therapy in the heart.

Bio-inspired slanted polymer nanohairs for anisotropic wetting and directional dry adhesion

Slanted polymer nanohairs possess a number of attractive properties in terms of anisotropic wetting and directional adhesion. This highlight provides an overview of the recent progress in the development of bio-inspired slanted polymer nanohairs and their applications towards anisotropic wetting and directional dry adhesion properties. With the advanced nano-fabrication techniques, it is possible to fabricate angled, directionally bent polymer nanohairs in a highly reproducible and geometry-controllable manner. The fabrication methods can be categorized into two streams: direct replica molding from a master with slanted structure or nanofabrication (photolithography or molding) with post treatment such as e-beam exposure, thermal annealing and mechanical compression. In this highlight, the fabrication methods for angled, high aspect ratio polymer nanohairs are briefly described along with their potential applications in anisotropic wetting and directional adhesion. Particular emphasis is given to recent achievements and future directions in biomimetic functional surfaces.