CCN2/CTGF-A Modulator of the Optic Nerve Head Astrocyte.

In primary open-angle glaucoma (POAG), a neurodegenerative disease of the optic nerve (ON) and leading cause of blindness, the optic nerve head (ONH) undergoes marked structural extracellular matrix (ECM) changes, which contribute to its permanent deformation and to degeneration of ON axons. The remodeling process of the ECM causes changes in the biomechanical properties of the ONH and the peripapillary sclera, which is accompanied by an increased reactivity of the resident astrocytes. The molecular factors involved in the remodeling process belong to the Transforming growth factor (TGF)-ß superfamily, especially TGF-ß2. In previous publications we showed that TGF-ß2 induced ECM alterations are mediated by Cellular Communication Network Factor (CCN)2/Connective Tissue Growth Factor (CTGF) and recently we showed that CCN2/CTGF is expressed by astrocytes of the ON under normal conditions. In this study we wanted to get a better understanding of the function of CCN2/CTGF under normal and pathologic conditions. To this end, we analyzed the glial lamina and peripapillary sclera of CCN2/CTGF overexpressing mice and studied the effect of CCN2/CTGF and increasing substratum stiffness on murine ON astrocytes in vitro. We observed enhanced astrocyte reactivity in the ONH, increased ECM protein synthesis in the peripapillary sclera and increased Ccn2/Ctgf expression in the ONH during the pathologic development in situ. CCN2/CTGF treatment of primary murine ON astrocytes induced a higher migration rate, and increase of ECM proteins including fibronectin, elastin and collagen type III. Furthermore, the astrocytes responded to stiffer substratum with increased glial fibrillary acidic protein, vimentin, actin and CCN2/CTGF synthesis. Finally, we observed the reinforced appearance of CCN2/CTGF in the lamina cribrosa of glaucomatous patients. We conclude that reactive changes in ONH astrocytes, induced by the altered biomechanical characteristics of the region, give rise to a self-amplifying process that includes increased TGF-ß2/CCN2/CTGF signaling and leads to the synthesis of ECM molecules and cytoskeleton proteins, a process that in turn augments the stiffness at the ONH. Such a scenario may finally result in a vicious circle in the pathogenesis of POAG. The transgenic CTGF-overexpressing mouse model might be an optimal model to study the chronic pathological POAG changes in the ONH.

Bio-Inspired Shape-Adaptive Soft Robotic Grippers Augmented with Electroadhesion Functionality.

Soft robotic grippers (SRGs) have been extensively employed in robotic grasping and manipulation applications due to the fact that they are beneficial for pick-and-place of difficult-to-handle and delicate objects with various geometries and stiffness in a comfortable and safer way. This article presents a bio-inspired and shape-adaptive SRG augmented with electroadhesion (EA) functionality, FinEA, by a cost-effective combination of a Fin Ray structured two-fingered SRG with two soft-stretchable EA pads. The EA pads were manufactured by screen printing a layer of electrically conductive and elastomeric carbon black powder mixed with polydimethylsiloxane onto a dielectric substrate. The compliant Fin Ray fingers, composed of soft longitudinal beams and rigid cross beams, were structurally optimized by the finite element method using ABAQUS/CAE based on three key parameters: the open angle of the longitudinal beams, the spacing between the cross beams, and the incline angle of the cross beams. The soft beams were produced by a traditional soft lithography method, whereas the rigid cross beams were three-dimensionally printed. The resultant FinEA grippers were capable of lifting not only flat/thin materials without distorting them due to the employment of EA, but also concave and convex objects due to the passively shape-adaptive Fin Ray structure and the EA functionality. In addition, the proposed FinEA grippers were able to grasp delicate materials and objects whose diameters are larger than the overall gripper length. Furthermore, 65% more weight in shear were picked up by the FinEA gripper when 4 kV was applied compared with 0 V. The FinEA concept provides useful and alternative solution for controllable adhesion-based SRGs and may facilitate the inspiration and development of future SRGs with added functionality and enhanced versatility.

Experimental study of the magnetic field enhanced Payne effect in magnetorheological elastomers.

The dynamic modulus and the loss factor of magnetorheological elastomers (MREs) of various compositions and anisotropies are studied by dynamic torsion oscillations performed in the absence and in the presence of an external magnetic field. The emphasis is on the Payne effect, i.e. the dependence of the elastomer magnetorheological characteristics on the strain amplitude and their evolution with cyclically increasing and decreasing strain amplitudes. MREs are based on two silicone matrices differing in storage modulus (soft, G' ∼ 10(3) Pa, and hard, G' ∼ 10(4) Pa, matrices). For each matrix, the concentration of carbonyl iron particles with diameters of 3-5 µm was equal to 70 and 82 mass% (22 and 35 vol%, respectively) in the composite material. Samples for each filler content, isotropic and aligned-particles, are investigated. It is found that the Payne effect significantly increases in the presence of an external magnetic field and varies with the cyclical loading which reaches saturation after several cycles. The results are interpreted as the processes of formation-destruction-reformation of the internal filler structure under the simultaneously applied mechanical force and magnetic field. Impacts of matrix elasticity and magnetic interactions on the filler alignment are elucidated.

Ultra-soft PDMS-based magnetoactive elastomers as dynamic cell culture substrata.

Mechanical cues such as extracellular matrix stiffness and movement have a major impact on cell differentiation and function. To replicate these biological features in vitro, soft substrata with tunable elasticity and the possibility for controlled surface translocation are desirable. Here we report on the use of ultra-soft (Young's modulus <100 kPa) PDMS-based magnetoactive elastomers (MAE) as suitable cell culture substrata. Soft non-viscous PDMS (<18 kPa) is produced using a modified extended crosslinker. MAEs are generated by embedding magnetic microparticles into a soft PDMS matrix. Both substrata yield an elasticity-dependent (14 vs. 100 kPa) modulation of α-smooth muscle actin expression in primary human fibroblasts. To allow for static or dynamic control of MAE material properties, we devise low magnetic field (≈40 mT) stimulation systems compatible with cell-culture environments. Magnetic field-instigated stiffening (14 to 200 kPa) of soft MAE enhances the spreading of primary human fibroblasts and decreases PAX-7 transcription in human mesenchymal stem cells. Pulsatile MAE movements are generated using oscillating magnetic fields and are well tolerated by adherent human fibroblasts. This MAE system provides spatial and temporal control of substratum material characteristics and permits novel designs when used as dynamic cell culture substrata or cell culture-coated actuator in tissue engineering applications or biomedical devices.

Nonlinear magnetoelectric response of planar ferromagnetic-piezoelectric structures to sub-millisecond magnetic pulses.

The magnetoelectric response of bi- and symmetric trilayer composite structures to pulsed magnetic fields is experimentally investigated in detail. The structures comprise layers of commercially available piezoelectric (lead zirconate titanate) and magnetostrictive (permendur or nickel) materials. The magnetic-field pulses have the form of a half-wave sine function with duration of 450 µs and amplitudes ranging from 500 Oe to 38 kOe. The time dependence of the resulting voltage is presented and explained by theoretical estimations. Appearance of voltage oscillations with frequencies much larger than the reciprocal pulse length is observed for sufficiently large amplitudes (~1-10 kOe) of the magnetic-field pulse. The origin of these oscillations is the excitation of bending and planar acoustic oscillations in the structures. Dependencies of the magnetoelectric voltage coefficient on the excitation frequency and the applied magnetic field are calculated by digital signal processing and compared with those obtained by the method of harmonic field modulation. The results are of interest for developing magnetoelectric sensors of pulsed magnetic fields as well as for rapid characterization of magnetoelectric composite structures.

Technologies for haptic systems in telemedicine.

The ability to image the elastic properties of tissue is potentially useful in a variety of applications. The field of elastic imaging has grown in response to the potential use of such information in medical diagnosis. Real time ultrasound elastography represents a recent development in determining strain and elasticity distributions. Nevertheless, commonly used imaging techniques rely on the interpretation of two dimensional visual data displayed on a video screen. In reality however, physicians often prefer tactile exploration making the simultaneous portrayal of both video and haptic information most desirable. Since the 1970's many alphanumeric to tactile data conversion methods have been investigated, mainly with the ultimate aim of assisting the blind. More recently, interest has been directed toward the display of pictures on haptically explorable surfaces--Tactile imaging. Such a system would allow surgeons to examine hard sectors contained within soft tissue, and thereby assist in operations held remotely. The expansion of ultrasound elastography to 3D formats would mean the ability to haptically explore regions of the body normally inaccessible to human hands. For three-dimensional imaging the acquisition of sequential tomographic slices using Elastography, combined with image segmentation, enables the reconstruction, quantification and visualisation of tumour volumes. In a collaborative project between four research institutes, the aim is to produce a prototype three dimensional tactile displays comprising electrically switchable micromachined cells, whose mechanical moduli are governed by phase changes experienced by electrorheological and/or magnetorheological fluids. This will be integrated with a sensory ultrasonic elastography in order to present the human fingers with controllable surfaces capable of emulating biological tissue, muscle and bone.