Flexible and Extensible Ribbon-Cable Interconnects for Implantable Electrical Neural Interfaces.

The design and characterization of thin-film ribbon cables as electrical interconnects for implanted neural stimulation and recording devices are reported. Our goal is to develop flexible and extensible ribbon cables that integrate with thin-film, cortical penetrating microelectrode arrays (MEAs). Amorphous silicon carbide (a-SiC) and polyimide were employed as the structural elements of the ribbon cables and multilayer titanium/gold thin films as electrical traces.

Quantifying Spatial Patterns of Tissue Stiffness Within the Embryonic Mouse Kidney.

Biophysical factors, including changes in mechanical stiffness, have been shown to influence the morphogenesis of developing organs. There is a lack of experimental techniques, however, that can probe the mechanical properties of embryonic tissues-especially those which are not mechanically or optically accessible, such as the visceral organs of the developing mouse embryo. Here, using the embryonic kidney as a model system, we describe a method to use microindentation to quantify tissue-level regional differences in the mechanical properties of an embryonic organ.

Treatment with both TGF-β1 and PDGF-BB disrupts the stiffness-dependent myofibroblast differentiation of corneal keratocytes.

Unlabelled: During corneal wound healing, stromal keratocytes transform into a repair phenotype that is driven by the release of cytokines, like transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). Previous work has shown that TGF-β1 promotes the myofibroblast differentiation of corneal keratocytes in a manner that depends on PDGF signaling. In addition, changes in mechanical properties are known to regulate the TGF-β1-mediated differentiation of cultured keratocytes.

Corneal keratocytes, fibroblasts, and myofibroblasts exhibit distinct transcriptional profiles .

Purpose: After stromal injury to the cornea, the release of growth factors and pro-inflammatory cytokines promotes the activation of quiescent keratocytes into a migratory fibroblast and/or fibrotic myofibroblast phenotype. Persistence of the myofibroblast phenotype can lead to corneal fibrosis and scarring, which are leading causes of blindness worldwide. This study aims to establish comprehensive transcriptional profiles for cultured corneal keratocytes, fibroblasts, and myofibroblasts to gain insights into the mechanisms through which these phenotypic changes occur.

Fabrication of Micropatterns of Aligned Collagen Fibrils.

Many tissues in vivo contain aligned structures such as filaments, fibrils, and fibers, which expose cells to anisotropic structural and topographical cues that range from the nanometer to micrometer scales. Understanding how cell behavior is regulated by these cues during physiological and pathological processes (e.g.

Effects of Topography and PDGF on the Response of Corneal Keratocytes to Fibronectin-Coated Surfaces.

During corneal wound healing, corneal keratocytes are exposed to both biophysical and soluble cues that cause them to transform from a quiescent state to a repair phenotype. How keratocytes integrate these multiple cues simultaneously is not well understood. To investigate this process, primary rabbit corneal keratocytes were cultured on substrates patterned with aligned collagen fibrils and coated with adsorbed fibronectin.

Quantifying endodermal strains during heart tube formation in the developing chicken embryo.

In the early avian embryo, the developing heart forms when bilateral fields of cardiac progenitor cells, which reside in the lateral plate mesoderm, move toward the embryonic midline, and fuse above the anterior intestinal portal (AIP) to form a straight, muscle-wrapped tube. During this process, the precardiac mesoderm remains in close contact with the underlying endoderm. Previous work has shown that the endoderm around the AIP actively contracts to pull the cardiac progenitors toward the midline.

Focal sources of FGF-10 promote the buckling morphogenesis of the embryonic airway epithelium.

During airway branching morphogenesis, focal regions of FGF-10 expression in the pulmonary mesenchyme are thought to provide a local guidance cue, which promotes chemotactically the directional outgrowth of the airway epithelium. Here, however, we show that an ectopic source of FGF-10 induces epithelial buckling morphogenesis and the formation of multiple new supernumerary buds. FGF-10-induced budding can be modulated by altered epithelial tension and luminal fluid pressure.

Toward Measuring the Mechanical Stresses Exerted by Branching Embryonic Airway Epithelial Explants in 3D Matrices of Matrigel.

Numerous organs in the bodies of animals, including the lung, kidney, and mammary gland, contain ramified networks of epithelial tubes. These structures arise during development via a process known as branching morphogenesis. Previous studies have shown that mechanical forces directly impact this process, but the patterns of mechanical stress exerted by branching embryonic epithelia are not well understood.

Signaling Downstream of Focal Adhesions Regulates Stiffness-Dependent Differences in the TGF-1-Mediated Myofibroblast Differentiation of Corneal Keratocytes.

Following injury and refractive surgery, corneal wound healing can initiate a protracted fibrotic response that interferes with ocular function. This fibrosis is related, in part, to the myofibroblast differentiation of corneal keratocytes in response to transforming growth factor beta 1 (TGF-1). Previous studies have shown that changes in the mechanical properties of the extracellular matrix (ECM) can regulate this process, but the mechanotransductive pathways that govern stiffness-dependent changes in keratocyte differentiation remain unclear.

ECM stiffness modulates the proliferation but not the motility of primary corneal keratocytes in response to PDGF-BB.

During corneal wound healing, keratocytes present within the corneal stroma become activated into a repair phenotype upon the release of growth factors, such as transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). The process of injury and repair can lead to changes in the mechanical properties of the tissue, and previous work has shown that the TGF-β1-mediated myofibroblast differentiation of corneal keratocytes depends on substratum stiffness. It is still unclear, however, if changes in stiffness can modulate keratocyte behavior in response to other growth factors, such as PDGF-BB.

Insertion mechanics of amorphous SiC ultra-micro scale neural probes.

. Trauma induced by the insertion of microelectrodes into cortical neural tissue is a significant problem. Further, micromotion and mechanical mismatch between microelectrode probes and neural tissue is implicated in an adverse foreign body response (FBR).

ECM Stiffness Controls the Activation and Contractility of Corneal Keratocytes in Response to TGF-β1.

After surgery or traumatic injury, corneal wound healing can cause a scarring response that stiffens the tissue and impairs ocular function. This fibrosis is caused in part by the activation of corneal keratocytes from a native mechanically quiescent state to an activated myofibroblastic state. This transformation is tied to signaling downstream of transforming growth factor-β1 (TGF-β1).

Keratocyte mechanobiology.

In vivo, corneal keratocytes reside within a complex 3D extracellular matrix (ECM) consisting of highly aligned collagen lamellae, growth factors, and other extracellular matrix components, and are subjected to various mechanical stimuli during developmental morphogenesis, fluctuations in intraocular pressure, and wound healing. The process by which keratocytes convert changes in mechanical stimuli (e.g.

Anisotropic, porous hydrogels templated by lyotropic chromonic liquid crystals.

Approaches to control the microstructure of hydrogels enable the control of cell-material interactions and the design of stimuli-responsive materials. We report a versatile approach for the synthesis of anisotropic polyacrylamide hydrogels using lyotropic chromonic liquid crystal (LCLC) templating. The orientational order of LCLCs in a mold can be patterned by controlling surface anchoring conditions, which in turn patterns the polymer network.

Deployable, liquid crystal elastomer-based intracortical probes.

Intracortical microelectrode arrays (MEAs) are currently limited in their chronic functionality due partially to the foreign body response (FBR) that develops in regions immediately surrounding the implant (typically within 50-100 µm). Mechanically flexible, polymer-based substrates have recently been explored for MEAs as a way of minimizing the FBR caused by the chronic implantation. Nonetheless, the FBR degrades the ability of the device to record neural activity.

A high-throughput microfluidic method for fabricating aligned collagen fibrils to study Keratocyte behavior.

In vivo, keratocytes are surrounded by aligned type I collagen fibrils that are organized into lamellae. A growing body of literature suggests that the unique topography of the corneal stroma is an important regulator of keratocyte behavior. In this study we describe a microfluidic method to deposit aligned fibrils of type I collagen onto glass coverslips.

A Meta-Analysis of Intracortical Device Stiffness and Its Correlation with Histological Outcomes.

Neural implants offer solutions for a variety of clinical issues. While commercially available devices can record neural signals for short time periods, they fail to do so chronically, partially due to the sustained tissue response around the device. Our objective was to assess the correlation between device stiffness, a function of both material modulus and cross-sectional area, and the severity of immune response.

An In Vitro Model for Assessing Corneal Keratocyte Spreading and Migration on Aligned Fibrillar Collagen.

Background: Corneal stromal cells (keratocytes) are responsible for developing and maintaining normal corneal structure and transparency, and for repairing the tissue after injury. Corneal keratocytes reside between highly aligned collagen lamellae in vivo. In addition to growth factors and other soluble biochemical factors, feedback from the extracellular matrix (ECM) itself has been shown to modulate corneal keratocyte behavior.

Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development.

Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissue types present within a developing organ remains unclear. Here, we use bioengineered 'microfluidic chest cavities' to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis, the frequency of airway smooth muscle contraction, and the rate of developmental maturation of the lungs, as assessed by transcriptional analyses.

Thinking Small: Progress on Microscale Neurostimulation Technology.

Objectives: Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational, and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume which may improve selectivity of therapeutic stimuli.

Computational models of airway branching morphogenesis.

The bronchial network of the mammalian lung consists of millions of dichotomous branches arranged in a highly complex, space-filling tree. Recent computational models of branching morphogenesis in the lung have helped uncover the biological mechanisms that construct this ramified architecture. In this review, we focus on three different theoretical approaches - geometric modeling, reaction-diffusion modeling, and continuum mechanical modeling - and discuss how, taken together, these models have identified the geometric principles necessary to build an efficient bronchial network, as well as the patterning mechanisms that specify airway geometry in the developing embryo.

Localized Smooth Muscle Differentiation Is Essential for Epithelial Bifurcation during Branching Morphogenesis of the Mammalian Lung.

The airway epithelium develops into a tree-like structure via branching morphogenesis. Here, we show a critical role for localized differentiation of airway smooth muscle during epithelial bifurcation in the embryonic mouse lung. We found that during terminal bifurcation, changes in the geometry of nascent buds coincided with patterned smooth muscle differentiation.

Pushing, pulling, and squeezing our way to understanding mechanotransduction.

Mechanotransduction is often described in the context of force-induced changes in molecular conformation, but molecular-scale mechanical stimuli arise in vivo in the context of complex, multicellular tissue structures. For this reason, we highlight and review experimental methods for investigating mechanotransduction across multiple length scales. We begin by discussing techniques that probe the response of individual molecules to applied force.