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ABSTRACT: We report on the effect of synthetic extracellular matrix (ECM) scaffold in the form of uniformly-spaced nanogrooved surfaces in dermal wound healing. The rate of wound coverage was measured on various nanotopographical densities with vertical or parallel orientation using nanogrooves of 550 nm width with three different gaps of 550, 1100, and 2750 nm (spacing ratio: 1:1, 1:2 and 1:5). Guided by the nanotopographical cues in the absence of growth factors in wound healing process, the cultured NIH-3T3 cells demonstrated distinctly different migration speed, cell division, and ECM production as dictated by the topographical density and orientation, whereas the proliferation rate turned out to be nearly the same. Based on our experimental results, the nanopattern of 1:2 spacing ratio yielded the best wound healing performance in terms of migration speed, which seems similar to the natural organization of collagen fibers.
Biomaterials 09/2012; 33(34):8782-92. · 7.40 Impact Factor
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ABSTRACT: 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.
Advanced drug delivery reviews 08/2012; · 11.96 Impact Factor
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ABSTRACT: 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.
Integrative Biology 08/2012; 4(9):1019-33. · 4.51 Impact Factor
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ABSTRACT: Flexible skin-attachable strain-gauge sensors are an essential component in the development of artificial systems that can mimic the complex characteristics of the human skin. In general, such sensors contain a number of circuits or complex layered matrix arrays. Here, we present a simple architecture for a flexible and highly sensitive strain sensor that enables the detection of pressure, shear and torsion. The device is based on two interlocked arrays of high-aspect-ratio Pt-coated polymeric nanofibres that are supported on thin polydimethylsiloxane layers. When different sensing stimuli are applied, the degree of interconnection and the electrical resistance of the sensor changes in a reversible, directional manner with specific, discernible strain-gauge factors. The sensor response is highly repeatable and reproducible up to 10,000 cycles with excellent on/off switching behaviour. We show that the sensor can be used to monitor signals ranging from human heartbeats to the impact of a bouncing water droplet on a superhydrophobic surface.
Nature Material 07/2012; 11(9):795-801. · 32.84 Impact Factor
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ABSTRACT: Polymers provide a versatile platform for mimicking various aspects of physiological extracellular matrix properties such as chemical composition, rigidity, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of patterning methods of various polymers with a particular focus on biocompatibility and processability. The materials highlighted here are widely used polymers including thermally curable polydimethyl siloxane, ultraviolet-curable polyurethane acrylate and polyethylene glycol, thermo-sensitive poly(N-isopropylacrylamide) and thermoplastic and conductive polymers. We also discuss how micro- and nanofabricated polymeric substrates of tunable elastic modulus can be used to engineer cell and tissue structure and function. Such synergistic effect of topography and rigidity of polymers may be able to contribute to constructing more physiologically relevant microenvironment.
Annals of biomedical engineering 01/2012; 40(6):1339-55. · 2.41 Impact Factor
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Advanced Functional Materials 09/2011; 21(19):3606 - 3616. · 10.18 Impact Factor
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ABSTRACT: We present a simple method to generate cracks with controllable size (depth and width) and space gradients using deep surface oxidation and anisotropic mechanical stretching. To generate a thick oxidation layer (<∼7 µm), a polydimethylsiloxane (PDMS) slab of uniform or varying thickness was exposed to UV/ozone for less than 30 min in the UV-C wavelength including wavelengths of 185 and 254 nm. Subsequently, the PDMS slab was wrapped on a cylindrical support (radius: 11 mm) to apply a uniform bending strain (<21%), resulting in equally separated, anisotropic cracks over a large area. By modulating initial oxidation depth and applied bending stress, cracks of varying sizes and spaces were formed on a single PDMS slab. Furthermore, multiple, sequential cracks were generated by increasing the strain in a step-wise fashion and multi-directional cracks by applying the strain with an orientation angle. Finally, size and space-varying cracks were formed between two adjacent large channels in an interconnected format by selective masking and irreversible bonding.
Lab on a Chip 11/2010; 11(4):717-22. · 5.67 Impact Factor
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ABSTRACT: A direct molding method for creating a homogeneous, polymer microfluidic channel is presented. By utilizing capillary rise and subsequent absorption of poly(methyl methacrylate) (PMMA) solution into a solvent-permeable poly(dimethyl siloxane) (PDMS) mold, various circular or elliptic polymer microchannels were fabricated without channel bonding and additional surface modification processes. In addition, the channel diameter was tunable from several micrometres to several hundreds of micrometres by controlling concentration and initial amount of polymer solution for a given PDMS mold geometry. The molded PMMA channels were used for two applications: blocking absorption of Rhodamine B dye and constructing artificial endothelial cell-cultured capillaries. It was observed that the molded PMMA channels effectively prevented absorption and diffusion of Rhodamine molecules over 5 h time span, demonstrating approximately 40 times higher blocking efficiency as compared to porous PDMS channels. Also, calf pulmonary artery endothelial cells (CPAEs) adhered, spread, and proliferated uniformly within the molded microchannels to form near confluency within 3 days and remained viable at day 6 without notable cell death, suggesting high biocompatibility and possibility for emulating in vivo-like three-dimensional architecture of blood vessels.
Lab on a Chip 10/2010; 10(23):3300-6. · 5.67 Impact Factor
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ABSTRACT: 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.
Biomaterials 03/2010; 31(15):4360-6. · 7.40 Impact Factor
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ABSTRACT: We investigated the capillary rise of a thin polymer solution in a simple soft lithographic technique termed "solvent-assisted molding (SAMo)" by using various mold rising angles and polymer concentrations in a good solvent. For patterning and mold materials, poly(methyl methacrylate) (PMMA, M(w) = 120,000) in toluene and poly(dimethyl siloxane) (PDMS) were mostly used. It was found that the capillary rise takes place in two steps: (i) a low-viscosity polymer solution rapidly rises into the cavity (<10 s) with the aid of solvent wetting and (ii) continuous solvent absorption into the mold and evaporation into air. In addition, five distinct microstructures were observed by testing 24 different experimental combinations, which can be classified into completely molded (I), humped (II), completely molded but non-fully filled (III), partially filled (IV), and partially filled meniscal (V) microstructures.
Langmuir 10/2009; 25(20):12024-9. · 4.19 Impact Factor
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ABSTRACT: 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 (approximately 26 N/cm(2) in maximum) in the angled direction and easy detachment (approximately 2.2 N/cm(2)) in the opposite direction, with a hysteresis value of approximately 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 microm) 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 x 37.5 cm(2), second-generation TFT-LCD glass), which could replace the current electrostatic transport/holding system with further optimization.
Proceedings of the National Academy of Sciences 05/2009; 106(14):5639-44. · 9.68 Impact Factor
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ABSTRACT: To estimate the extent of genetic variation at the DNA level, the histone 3 (H3) genes were sequenced from single individual each from the three cryptic species recognized based on allozyme analyses, YFS, J and T types of Conocephalum conicum and two closely related species, C. japonicum and Marchantia polymorpha. Although the H3 genes are known to be highly conserved, the nucleotide diversities were 0.128, 0.109, 0.108, 0.049 and 0.034. These values are 30 to 100 times higher than that in Drosophila melanogaster (0.001). Besides, there were considerable differences in the position, length and number of introns among the loci of H3 genes. The observed high level of nucleotide diversities was explained by the fixation of many random mutations, and non-concerted evolution that resulted from low rates of unequal crossing-over and gene conversion probably due to the dispersed structure of H3 genes on genome in this species. The non-concerted evolutionary pattern was established by the analysis of phylogenetic tree and divergence rates. This study confirmed previous results suggesting that natural populations of liverwort maintains high extent of variation at DNA level.
Genes & Genetic Systems 01/2005; 79(6):331-44. · 0.95 Impact Factor
