Penetrating Microindentation of Hyper-soft, Conductive Silicone Neural Interfaces in Vivo Reveals Significantly Lower Mechanical Stresses

MRS Advances ◽  
2019 ◽  
Vol 4 (46-47) ◽  
pp. 2551-2558
Author(s):  
Arati Sridharan ◽  
Vikram Kodibagkar ◽  
Jit Muthuswamy
Keyword(s):  
Steady State ◽  
Elastic Modulus ◽  
Mechanical Stresses ◽  
Neural Interface ◽  
Neural Interfaces ◽  
Neural Implants ◽  
Axial Forces ◽  
Multi Walled Carbon Nanotubes ◽  
Microindentation Technique

ABSTRACTThere is growing evidence that minimizing the mechanical mismatch between neural implants and brain tissue mitigates inflammatory, biological responses at the interface under long-term implant conditions. The goal of this study is to develop a brain-like soft, conductive neural interface and use an improvised, penetrating microindentation technique reported by us earlier to quantitatively assess the (a) elastic modulus of the neural interface after implantation, (b) mechanical stresses during penetration of the probe, and (c) periodic stresses at steady-state due to tissue micromotion around the probe. We fabricated poly- dimethylsiloxane (PDMS) matrices with multi-walled carbon nanotubes (MWCNTs) using two distinct but carefully calibrated cross-linking ratios, resulting in hard (elastic modulus∼484 kPa) or soft, brain-like (elastic modulus∼5.7 kPa) matrices, the latter being at least 2 orders of magnitude softer than soft neural interfaces reported so far. Subsequent loading of the hard and soft silicone based matrices with (100% w/w) low-molecular weight PDMS siloxanes resulted in further decrease in the elastic modulus of both matrices. Carbon probes with soft PDMS coating show significantly less maximum axial forces (-587 ± 51.5 µN) imposed on the brain than hard PDMS coated probes (-1,253 ± 252 µN) during and after insertion. Steady-state, physiological micromotion related stresses were also significantly less for soft- PDMS coated probes (55.5 ± 17.4 Pa) compared to hard-PDMS coated probes (141.0 ± 21.7 Pa). The penetrating microindentation technique is valuable to quantitatively assess the mechanical properties of neural interfaces in both acute and chronic conditions.

scholarly journals A 3D flexible neural interface based on a microfluidic interconnection cable capable of chemical delivery

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yoo Na Kang ◽  
Namsun Chou ◽  
Jae-Won Jang ◽  
Han Kyoung Choe ◽  
Sohee Kim
Keyword(s):  
Microelectrode Array ◽  
Neurological Diseases ◽  
Three Dimensional ◽  
Critical Issue ◽  
Neural Interface ◽  
Neural Interfaces ◽  
Dimensional Structure ◽  
Microfluidic Channels ◽  
Before And After

AbstractThe demand for multifunctional neural interfaces has grown due to the need to provide a better understanding of biological mechanisms related to neurological diseases and neural networks. Direct intracerebral drug injection using microfluidic neural interfaces is an effective way to deliver drugs to the brain, and it expands the utility of drugs by bypassing the blood–brain barrier (BBB). In addition, uses of implantable neural interfacing devices have been challenging due to inevitable acute and chronic tissue responses around the electrodes, pointing to a critical issue still to be overcome. Although neural interfaces comprised of a collection of microneedles in an array have been used for various applications, it has been challenging to integrate microfluidic channels with them due to their characteristic three-dimensional structures, which differ from two-dimensionally fabricated shank-type neural probes. Here we present a method to provide such three-dimensional needle-type arrays with chemical delivery functionality. We fabricated a microfluidic interconnection cable (µFIC) and integrated it with a flexible penetrating microelectrode array (FPMA) that has a 3-dimensional structure comprised of silicon microneedle electrodes supported by a flexible array base. We successfully demonstrated chemical delivery through the developed device by recording neural signals acutely from in vivo brains before and after KCl injection. This suggests the potential of the developed microfluidic neural interface to contribute to neuroscience research by providing simultaneous signal recording and chemical delivery capabilities.

Preparation and Biochemical Evaluation of Functionalized Multi-Walled Carbon Nanotubes with Punica granatum Extract

2019 ◽  
Vol 15 (1) ◽  
pp. 138-144 ◽  
Author(s):  
Ahmed A. Haroun ◽  
Abdel-Tawab H. Mossa ◽  
Samia M.M. Mohafrash
Keyword(s):  
Liver Enzymes ◽  
Histopathological Analysis ◽  
Pomegranate Peel ◽  
Liver And Kidney ◽  
Multi Walled Carbon Nanotubes ◽  
Pomegranate Peel Extract ◽  
Walled Carbon Nanotubes ◽  
Functionalized Mwcnts ◽  
Peel Extract

Background: Funcionalized multi-walled carbon nanotubes (ox-MWCNTs) were used for the preparation of therapeutic nanoparticles for delivery of some bioactive compounds. Consequently, this work deals with the preparation of grafted MWCNTs with n-vinyl caprolactam in the presence of pomegranate peel extract (P. granatum), titanium dioxide (TiO2) and/or silver nanoparticeles and their toxic effects on male mice using in vivo biological examination (liver and kidney dysfunction biomarkers) and the histopathological analysis. Methods: P. granatum extract was immobilized onto functionalized MWCNTs using simple adsorption technique. Moreover, The prepared materials were analyzed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM). In vivo examination using liver and kidney dysfunction biomarkers was investigated. In addition, the histopathological study was carried out. Results: The ox-MWCNTs induced significant elevation in the liver enzymes including AST, ALT and ALP relative to the control group. While, the treatment with P. granatum extract only did not induce any change in the liver and kidney biomarkers. In other words, P. granatum extract loaded onto functionalized MWCNTs showed low effects on liver enzymes and kidney function biomarkers in the treated mice in comparison with ox-MWCNTs and extract separately. Moreover, histopathological analysis revealed that the P. granatum extract functionalized MWCNTs exhibited normal renal tissue with no histopathological alteration. Conclusion: The grafted MWCNTs with n-vinyl caprolactam in the presence of pomegranate peel extract (P. granatum), titanium dioxide (TiO2) and/or silver nanoparticeles were successfully prepared. SEM-micrographs showed complete coating of MWCNTs fiber with the extract. The prepared materials resulted in no toxic effects and the histopathological findings were confirmed by inflammation of the liver and kidney tissues.

scholarly journals Progress and challenges of implantable neural interfaces based on nature-derived materials

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Eugenio Redolfi Riva ◽  
Silvestro Micera
Keyword(s):  
Interface Design ◽  
Specific Area ◽  
Building Blocks ◽  
Matrix Proteins ◽  
Neural Interface ◽  
Neural Interfaces ◽  
Biomedical Science ◽  
Chronic Inflammatory Response ◽  
The Impact

AbstractNeural interfaces are bioelectronic devices capable of stimulating a population of neurons or nerve fascicles and recording electrical signals in a specific area. Despite their success in restoring sensory-motor functions in people with disabilities, their long-term exploitation is still limited by poor biocompatibility, mechanical mismatch between the device and neural tissue and the risk of a chronic inflammatory response upon implantation.In this context, the use of nature-derived materials can help address these issues. Examples of these materials, such as extracellular matrix proteins, peptides, lipids and polysaccharides, have been employed for decades in biomedical science. Their excellent biocompatibility, biodegradability in the absence of toxic compound release, physiochemical properties that are similar to those of human tissues and reduced immunogenicity make them outstanding candidates to improve neural interface biocompatibility and long-term implantation safety. The objective of this review is to highlight progress and challenges concerning the impact of nature-derived materials on neural interface design. The use of these materials as biocompatible coatings and as building blocks of insulation materials for use in implantable neural interfaces is discussed. Moreover, future perspectives are presented to show the increasingly important uses of these materials for neural interface fabrication and their possible use for other applications in the framework of neural engineering.

scholarly journals Fabrication of 3D-Printed Interpenetrating Hydrogel Scaffolds for Promoting Chondrogenic Differentiation

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2146
Author(s):  
Jian Guan ◽  
Fu-zhen Yuan ◽  
Zi-mu Mao ◽  
Hai-lin Zhu ◽  
Lin Lin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Elastic Modulus ◽  
Chondrogenic Differentiation ◽  
Marker Genes ◽  
Self Healing ◽  
Polyethylene Glycol Diacrylate ◽  
3D Microenvironment ◽  
3D Printed

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.

scholarly journals Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity

2005 ◽  
Vol 169 (4) ◽  
pp. 569-576 ◽  
Author(s):  
Clare L. Bennett ◽  
Erwin van Rijn ◽  
Steffen Jung ◽  
Kayo Inaba ◽  
Ralph M. Steinman ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Steady State ◽  
Diphtheria Toxin ◽  
Langerhans Cells ◽  
Contact Hypersensitivity ◽  
Relative Importance ◽  
Skin Immunity

Langerhans cells (LC) form a unique subset of dendritic cells (DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC (dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/DT-based system to achieve inducible ablation of LC without affecting the skin environment. Within 24 h after intra-peritoneal injection of DT into Langerin-DTR mice LC are completely depleted from the epidermis and only begin to return 4 wk later. LC deletion occurs by apoptosis in the absence of inflammation and, in particular, the dDC compartment is not affected. In LC-depleted mice contact hypersensitivity (CHS) responses are significantly decreased, although ear swelling still occurs indicating that dDC can mediate CHS when necessary. Our results establish Langerin-DTR mice as a unique tool to study LC function in the steady state and to explore their relative importance compared with dDC in orchestrating skin immunity and tolerance.

Noradrenaline-induced calorigenesis in warm- or cold-acclimated rats. In vivo estimation of adrenoceptor concentration of noradrenaline effecting half-maximal response

1980 ◽  
Vol 58 (9) ◽  
pp. 1072-1077 ◽  
Author(s):  
Florent Depocas ◽  
Gloria Zaror-Behrens ◽  
Suzanne Lacelle
Keyword(s):  
Adipose Tissue ◽  
Steady State ◽  
Brown Adipose Tissue ◽  
Maximal Response ◽  
Brown Adipose ◽  
Acclimation Group ◽  
Arterial Plasma ◽  
State Concentration ◽  
Na Uptake

Desmethylimipramine (DMI, 1 mg DMI∙HCl kg−1) and normetanephrine (NMN, 1 μg min−1 g−0.74) were used to inhibit, respectively, neuronal and extraneuronal uptakes of noradrenaline (NA) during calorigenesis induced in barbital-sedated warm-acclimated (WA) or cold-acclimated (CA) rats by infusion of NA, a procedure which mimics the effects of NA released within calorigenic tissues in response to cold exposure. The doses of the inhibitors were selected for maximal effectiveness in potentiating calorigenic response and for minimal side effects. For rats of either acclimation group treated with DMI and NMN, with DMI only, or with neither inhibitor the doses of NA required to evoke approximately half-maximal calorigenic responses were, respectively, 0.5, 1.0, and 3.5 ng min−1 g−0.74. The corresponding steady-state concentrations of NA in arterial plasma averaged 14.3, 21.7, and 43.2 nM in the three groups of WA rats and 10.0, 14.8, and 31.9 nM in the three groups of CA rats. Reduction by NA uptake inhibitors of the circulating levels of NA necessary to stimulate calorigenesis, half-maximally, presumably in brown adipose tissue, indicates a reduction in the steepness of the NA concentration gradient between capillary plasma and synaptic clefts in that tissue. The steady-state concentration of NA in blood plasma of rats treated with DMI and NMN and infused with NA at a dose of 0.5 ng min−1 g−0.74 (~1 × 10−8 M) is a good estimate of the NA concentration required at calorigenic adrenoceptors to effect half-maximal activation. Presumably, this concentration is also an estimate of that resulting from NA released at nerve endings during cold-induced activation of nonshivering thermogenesis at half-maximal rates in brown adipose tissue.

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