Diamond/Porous Titanium Nitride Electrodes With Superior Electrochemical Performance for Neural Interfacing

Robust devices for chronic neural stimulation demand electrode materials which exhibit high charge injection (Qinj) capacity and long-term stability. Boron-doped diamond (BDD) electrodes have shown promise for neural stimulation applications, but their practical applications remain limited due to the poor charge transfer capability of diamond. In this work, we present an attractive approach to produce BDD electrodes with exceptionally high surface area using porous titanium nitride (TiN) as interlayer template. The TiN deposition parameters were systematically varied to fabricate a range of porous electrodes, which were subsequently coated by a BDD thin-film. The electrodes were investigated by surface analysis methods and electrochemical techniques before and after BDD deposition. Cyclic voltammetry (CV) measurements showed a wide potential window in saline solution (between −1.3 and 1.2 V vs. Ag/AgCl). Electrodes with the highest thickness and porosity exhibited the lowest impedance magnitude and a charge storage capacity (CSC) of 253 mC/cm2, which largely exceeds the values previously reported for porous BDD electrodes. Electrodes with relatively thinner and less porous coatings displayed the highest pulsing capacitances (Cpulse), which would be more favorable for stimulation applications. Although BDD/TiN electrodes displayed a higher impedance magnitude and a lower Cpulse as compared to the bare TiN electrodes, the wider potential window likely allows for higher Qinj without reaching unsafe potentials. The remarkable reduction in the impedance and improvement in the charge transfer capacity, together with the known properties of BDD films, makes this type of coating as an ideal candidate for development of reliable devices for chronic neural interfacing

ZAK beta is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle

Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAK beta is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKO's ability to recognize stress fibers in cells and Z-discs in muscle fibers when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.Peer reviewe

Histological evaluation of the male rabbit urethra: Regional and age-related variations and their relevance in tissue engineering and reconstructive surgery applications

Background data: The male rabbit is the most frequently utilized animal model for urethral preclinical experiments. Surprisingly, little is known about the regional variations in the tissue along the urethra, or how age influences these differences. Objective: To examine the histological changes during healthy ageing in the different regions of the rabbit urethra. Methods: Healthy New Zealand White rabbits of 3, 8 and 21 weeks of age were selected for the study. The rabbits’ urethrae were analyzed by histochemical and immunohistochemical methods, with focus on the smooth and skeletal muscle layers, and the extracellular matrix (ECM) components. Results: The rabbits' urethrae displayed significant similarities to human male urethra. The proximal and middle third of the urethrae were histologically characterized by an abundance of smooth muscle, while the distal third was composed of numerous sinusoids scattered among smooth muscle bundles that are decreasing in thickness and uniformity with increasing age. Age-related histological changes occurred in the urethra at a significant rate. Conclusion: Our results demonstrate that the male rabbit urethra displays significant regional differences, which are influenced by age. It is therefore crucial to select an appropriate age range when designing preclinical studies for the evaluation of urethral reconstruction approaches

From Acellular Matrices to Smart Polymers: Degradable Scaffolds that are Transforming the Shape of Urethral Tissue Engineering.

Several congenital and acquired conditions may result in severe narrowing of the urethra in men, which represent an ongoing surgical challenge and a significant burden on both health and quality of life. In the field of urethral reconstruction, tissue engineering has emerged as a promising alternative to overcome some of the limitations associated with autologous tissue grafts. In this direction, preclinical as well as clinical studies, have shown that degradable scaffolds are able to restore the normal urethral architecture, supporting neo-vascularization and stratification of the tissue. While a wide variety of degradable biomaterials are under scrutiny, such as decellularized matrices, natural, and synthetic polymers, the search for scaffold materials that could fulfill the clinical performance requirements continues. In this article, we discuss the design requirements of the scaffold that appear to be crucial to better resemble the structural, physical, and biological properties of the native urethra and are expected to support an adequate recovery of the urethral function. In this context, we review the biological performance of the degradable polymers currently applied for urethral reconstruction and outline the perspectives on novel functional polymers, which could find application in the design of customized urethral constructs

Hypoxia enhances the wound-healing potential of adipose-derived stem cells in a novel human primary keratinocyte-based scratch assay

WOS: 000397173200011PubMed ID: 28204820Preclinical studies have suggested that paracrine factors from adipose-derived stem cells (ASCs) promote the healing of chronic wounds, and that the exposure of ASCs to hypoxia enhances their wound healing effect. To aid the translation of these findings into clinical use, robust wound models are necessary to explore each aspect of wound healing. The aspect of re-epithelization is often studied in a scratch assay based on transformed keratinocytes. However, there are concerns regarding the validity of this model, since these cell lines differ from normal keratinocytes, both in terms of proliferative capacity and differentiation, and sensitivity to environmental cues. In this study, the main challenge of using primary keratinocytes to examine the effects of ASCs was identified to be their different requirements for calcium in the culture media. We confirmed that a high calcium content led to morphological and cytoskeletal changes in primary keratinocytes, and demonstrated that a low calcium content compromised the growth of ASCs. We found that it is possible to perform the wound healing assay with primary keratinocytes, if the conditioned media from the ASCs is dialyzed to reduce the calcium concentration. Additionally, using this model of re-epithelization, conditioned media from normoxic ASCs was shown to markedly increase the rate of wound closure by primary keratinocytes, and this effect was significantly enhanced with media from the hypoxia-exposed ASCs. These findings, which are in line with the observations from previous in vivo studies, highlight the validity of this modified assay to investigate the wound healing properties of ASCs in vitro.Lily Benthine Lunds fond; Grosserer L.F. Foghts Fond; Obelske family foundationThe authors acknowledge the technical assistance provided by O. Jensen and L. Sangenario. This study was supported in part by funds from Lily Benthine Lunds fond (S.R.), Grosserer L.F. Foghts Fond (V.Z.) and the Obelske family foundation (T.F.). The funding sources had no influence on either the study design, collection, analysis, interpretation of the data, the writing of the study, or on the decision to submit the study for publication. R.N., D.K., S.B. and M.V. are regular employees of ThermoFisher Scientific and have not received any financial gains. They hold some stocks of ThermoFisher Scientific as employees of ThermoFisher Scientific