Biofouling resistance of boron-doped diamond neural stimulation electrodes is superior to titanium nitride electrodes in vivo.

OBJECTIVE: The goal of this study was to assess the electrochemical properties of boron-doped diamond (BDD) electrodes in relation to conventional titanium nitride (TiN) electrodes through in vitro and in vivo measurements. APPROACH: Electrochemical impedance spectroscopy, cyclic voltammetry and voltage transient (VT) measurements were performed in vitro after immersion in a 5% albumin solution and in vivo after subcutaneous implantation in rats for 6 weeks. MAIN RESULTS: In contrast to the TiN electrodes, the capacitance of the BDD electrodes was not significantly reduced in albumin solution. Furthermore, BDD electrodes displayed a decrease in the VTs and an increase in the pulsing capacitances immediately upon implantation, which remained stable throughout the whole implantation period, whereas the opposite was the case for the TiN electrodes. SIGNIFICANCE: These results reveal that BDD electrodes possess a superior biofouling resistance, which provides significantly stable electrochemical properties both in protein solution as well as in vivo compared to TiN electrodes.

Critical steps in the isolation and expansion of adipose-derived stem cells for translational therapy.

Since the discovery of adipose-derived stem cells (ASCs), there have been high expectations of their putative clinical use. Recent advances support these expectations, and it is expected that the transition from pre-clinical and clinical studies to implementation as a standard treatment modality is imminent. However ASCs must be isolated and expanded according to good manufacturing practice guidelines and a basic assurance of quality, safety, and medical effectiveness is needed for authorisation by regulatory agencies, such as European Medicines Agency and US Food and Drug Administration. In this review, a collection of studies investigating the influence of different steps of the isolation and expansion protocol on the yield and functionality of ASCs has been presented in an attempt to come up with best recommendations that ensure potential beneficial clinical outcome of using ASCs in any therapeutic setting. If the findings confirm the initial observations of beneficial effects of ASCs, the path is paved for implementing these ASC-based therapies as standard treatment options.

Increased connective tissue attachment to silicone implants by a water vapor plasma treatment.

Polydimethylsiloxane (PDMS) is the most common type of silicone polymer for the fabrication of implantable medical devices. Because of its inherent hydrophobic nature, the PDMS surface does not readily promote cellular adhesion, which leads to diverse clinical issues. Previously, we reported a simple water vapor plasma treatment of PDMS surfaces that resulted in stable long-term wettability and excellent in vitro cell compatibility. In this work, we report investigation of the in vivo local responses to PDMS implants treated by water vapor plasma using a subcutaneous rat model. The local tissue responses were assessed after 2 and 4 weeks of implantation by means of macroscopic and histomorphometric analysis. After 2 weeks of implantation, the plasma-treated implants elicited the formation of fibrous tissue capsules that were significantly thinner, more adherent, and vascularized than the control counterparts. The improved cell adhesion was correlated with an increased amount of cells attached to the implant surface after retrieval. There was no difference in the inflammatory response between untreated and treated samples. This study provides a rational approach to optimize the long-term performance of silicone implants, which is likely to have a significant impact in clinical applications demanding enhanced tissue integration of the implants.

Responses of fibroblasts and glial cells to nanostructured platinum surfaces.

The chronic performance of implantable neural prostheses is affected by the growth of encapsulation tissue onto the stimulation electrodes. Encapsulation is associated with activation of connective tissue cells at the electrode's metallic contacts, usually made of platinum. Since surface nanotopography can modulate the cellular responses to materials, the aim of the present work was to evaluate the 'in vitro' responses of connective tissue cells to platinum strictly by modulating its surface nanoroughness. Using molecular beam epitaxy combined with sputtering, we produced platinum nanostructured substrates consisting of irregularly distributed nanopyramids and investigated their effect on the proliferation, cytoskeletal organization and cellular morphology of primary fibroblasts and transformed glial cells. Cells were cultured on these substrates and their responses to surface roughness were studied. After one day in culture, the fibroblasts were more elongated and their cytoskeleton less mature when cultured on rough substrates. This effect increased as the roughness of the surface increased and was associated with reduced cell proliferation throughout the observation period (4 days). Morphological changes also occurred in glial cells, but they were triggered by a different roughness scale and did not affect cellular proliferation. In conclusion, surface nanotopography modulates the responses of fibroblasts and glial cells to platinum, which may be an important factor in optimizing the tissue response to implanted neural electrodes.

The influence of glancing angle deposited nano-rough platinum surfaces on the adsorption of fibrinogen and the proliferation of primary human fibroblasts.

We have used the glancing angle deposition (GLAD) method as a simple and fast method to generate nano-rough surfaces for protein adsorption experiments and cell assays. The surface roughness and the detailed geometrical surface morphology of the thin films were characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). As the GLAD deposition angle approaches grazing incidence, sharp and whisker-like columnar protrusions are formed. Smaller and less sharp surface features appear for the thin films synthesized at higher deposition angles. By changing the GLAD deposition angle together with the total amount of mass deposited per area on the respective surfaces, the size of the surface features can be varied on the nanoscale. Using the GLAD topographies as model surfaces, we have investigated the influence of the nano-roughness on fibrinogen adsorption and on the proliferation of primary human fibroblasts. It is found that fibrinogen, an important blood protein, preferentially adheres on the whisker-like nano-rough substrates in comparison to a flat surface. Furthermore, the proliferation of the human fibroblasts is significantly reduced on the nano-rough substrates. These results demonstrate that the GLAD technique can be used to fabricate nano-rough surface morphologies that significantly influence both protein and cellular adhesion to surfaces and are therefore well suited for biological assays.

Spatial distribution of the electric potential from photosystem I reaction centers in lipid vesicles.

Photosynthetic reaction centers are integral membrane complexes that produce a net transmembrane charge separation in response to light. The Photosystem I (PSI) complex is a thoroughly studied reaction center that has been proposed as a nanoscale photovoltaic structure in diverse applications, including activation of excitable cells by triggering of voltage-gated ion channels. An electrostatic model of a spherical lipid vesicle embedded with PSI and suspended in an aqueous medium is presented. The distribution of the electric potential is obtained by solving the nonlinear Poisson-Boltzmann equation with the finite-element method. The model predicts a maximum potential difference of 1.3 V between charges. This value depends mostly on the intrinsic dielectric constants of the reaction center and distance between charges. However, the potential distribution near the reaction center depends on the ionic strength of the aqueous medium. When the ionic strength is zero, the vesicle develops a transmembrane potential that increases linearly with the density of reaction centers. When the ionic strength increases, this potential difference approaches to zero. The main results of the simulations are consistent with previously reported experimental data. Based on the presented results, the potential application of PSI to light activation of voltage-gated ion channels is discussed.