Phase aberration correction for ultrasound imaging guided extracorporeal shock wave therapy (ESWT): Feasibility study.

Image guidance of extracorporeal shock wave therapy (ESWT) is important to enhance its efficacy while lowering pain in patients. Real-time ultrasound imaging is an appropriate modality for image guidance, but its image quality substantially reduces due to severe phase aberration from the different speed of sound between soft tissues and a gel pad, which is utilized to control a therapeutic focal point in ESWT. This paper presents a phase aberration correction method for improving image quality in the ultrasound imaging guided ESWT.

Switch-like enhancement of epithelial-mesenchymal transition by YAP through feedback regulation of WT1 and Rho-family GTPases.

Collective cell migration occurs in many patho-physiological states, including wound healing and invasive cancer growth. The integrity of the expanding epithelial sheets depends on extracellular cues, including cell-cell and cell-matrix interactions. We show that the nano-scale topography of the extracellular matrix underlying epithelial cell layers can strongly affect the speed and morphology of the fronts of the expanding sheet, triggering partial and complete epithelial-mesenchymal transitions (EMTs).

Efficient Direct Lineage Reprogramming of Fibroblasts into Induced Cardiomyocytes Using Nanotopographical Cues.

Induced cardiomyocytes (iCMs) generated via direct lineage reprogramming offer a novel therapeutic target for the study and treatment of cardiac diseases. However, the efficiency of iCM generation is significantly low for therapeutic applications. Here, we show an efficient direct conversion of somatic fibroblasts into iCMs using nanotopographic cues.

Mechanochemical feedback underlies coexistence of qualitatively distinct cell polarity patterns within diverse cell populations.

Cell polarization and directional cell migration can display random, persistent, and oscillatory dynamic patterns. However, it is not clear whether these polarity patterns can be explained by the same underlying regulatory mechanism. Here, we show that random, persistent, and oscillatory migration accompanied by polarization can simultaneously occur in populations of melanoma cells derived from tumors with different degrees of aggressiveness.

Directional Matrix Nanotopography with Varied Sizes for Engineering Wound Healing.

Topographic features play a crucial role in the regulation of physiologically relevant cell and tissue functions. Here, an analysis of feature-size-dependent cell-nanoarchitecture interactions is reported using an array of scaffolds in the form of uniformly spaced ridge/groove structures for engineering wound healing. The ridge and groove widths of nanopatterns are varied from 300 to 800 nm and the nanotopography features are classified into three size ranges: dense (300-400 nm), intermediate (500-600 nm), and sparse (700-800 nm).

Hierarchically Micro- and Nanopatterned Topographical Cues for Modulation of Cellular Structure and Function.

Living cells receive biochemical and physical information from the surrounding microenvironment and respond to this information. Multiscale hierarchical substrates with micro- and nanogrooves have been shown to mimic the native extracellular matrix (ECM) better than conventional nanopatterned substrates; therefore, substrates with hierarchical topographical cues are considered suitable for investigating the role of physical factors in tissue functions. In this study, precisely controllable, multiscale hierarchical substrates that could mimic the micro- and nanotopography of complex ECMs were fabricated and used to culture various cell types, including fibroblasts, endothelial cells, osteoblasts, and human mesenchymal stem cells.

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.

Nanogrooved substrate promotes direct lineage reprogramming of fibroblasts to functional induced dopaminergic neurons.

The generation of dopaminergic (DA) neurons via direct lineage reprogramming can potentially provide a novel therapeutic platform for the study and treatment of Parkinson's disease. Here, we showed that nanoscale biophysical stimulation can promote the direct lineage reprogramming of somatic fibroblasts to induced DA (iDA) neurons. Fibroblasts that were cultured on flat, microgrooved, and nanogrooved substrates responded differently to the patterned substrates in terms of cell alignment.

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.

Quantitative analysis of the combined effect of substrate rigidity and topographic guidance on cell morphology.

Live cells are exquisitely sensitive to both the substratum rigidity and texture. To explore cell responses to both these types of inputs in a precisely controlled fashion, we analyzed the responses of Chinese hamster ovary (CHO) cells to nanotopographically defined substrata of different rigidities, ranging from 1.8 MPa to 1.

Controlled mechanical fracture for fabricating microchannels with various size gradients.

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.

Effects of mold rising angle and polymer concentration in solvent-assisted molding.

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.