SignificanceImplantable electronic medical devices (IEMDs) are used for some clinical applications, representing an exciting prospect for the transformative treatment of intractable conditions such ...Parkinson's disease, deafness, and paralysis. The use of IEMDs is limited at the moment because, over time, a foreign body reaction (FBR) develops at the device-neural interface such that ultimately the IEMD fails and needs to be removed. Here, we show that macrophage nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity drives the FBR in a nerve injury model yet integration of an NLRP3 inhibitor into the device prevents FBR while allowing full healing of damaged neural tissue to occur.
Bio-inspired nano tools for neuroscience Das, Suradip; Carnicer-Lombarte, Alejandro; Fawcett, James W ...
Progress in neurobiology,
07/2016, Volume:
142
Journal Article
Peer reviewed
Research and treatment in the nervous system is challenged by many physiological barriers posing a major hurdle for neurologists. The CNS is protected by a formidable blood brain barrier (BBB) which ...limits surgical, therapeutic and diagnostic interventions. The hostile environment created by reactive astrocytes in the CNS along with the limited regeneration capacity of the PNS makes functional recovery after tissue damage difficult and inefficient. Nanomaterials have the unique ability to interface with neural tissue in the nano-scale and are capable of influencing the function of a single neuron. The ability of nanoparticles to transcend the BBB through surface modifications has been exploited in various neuro-imaging techniques and for targeted drug delivery. The tunable topography of nanofibers provides accurate spatio-temporal guidance to regenerating axons. This review is an attempt to comprehend the progress in understanding the obstacles posed by the complex physiology of the nervous system and the innovations in design and fabrication of advanced nanomaterials drawing inspiration from natural phenomenon. We also discuss the development of nanomaterials for use in Neuro-diagnostics, Neuro-therapy and the fabrication of advanced nano-devices for use in opto-electronic and ultrasensitive electrophysiological applications. The energy efficient and parallel computing ability of the human brain has inspired the design of advanced nanotechnology based computational systems. However, extensive use of nanomaterials in neuroscience also raises serious toxicity issues as well as ethical concerns regarding nano implants in the brain. In conclusion we summarize these challenges and provide an insight into the huge potential of nanotechnology platforms in neuroscience.
Objective. High-density electrode arrays are a powerful tool in both clinical neuroscience and basic research. However, current manufacturing techniques require the use of specialised techniques and ...equipment, which are available to few labs. We have developed a high-density electrode array with customisable design, manufactured using simple printing techniques and with commercially available materials. Approach. Electrode arrays were manufactured by thick-film printing a platinum-gold alloy (Pt/Au) and an insulating dielectric on 96% alumina ceramic plates. Arrays were conditioned in serum and serum-free conditions, with and without 1 kHz, 200 µA, charge balanced stimulation for up to 21 d. Array biocompatibility was assessed using an extract assay and a PC-12 cell contact assay. Electrode impedance, charge storage capacity and charge injection capacity were before and after array conditioning. Main results. The manufactured Pt/Au electrodes have a highly porous surface and exhibit electrical properties comparable to arrays manufactured using alternative techniques. Materials used in array manufacture were found to be non-toxic to L929 fibroblasts by extract assay, and neuronal-like PC-12 cells adhered and extended neurites on the array surfaces. Arrays remained functional after long-term delivery of electrical pulses while exposed to protein-rich environments. Charge storage capacities and charge injection capacities increased following stimulation accounted for by an increase in surface index (real surface area) observed by vertical scanning interferometry. Further, we observed accumulation of proteins at the electrode sites following conditioning in the presence of serum. Significance. This study demonstrates the in vitro biocompatibility of commercially available thick-film printing materials. The printing technique is both simple and versatile, with layouts readily modified to produce customized electrode arrays. Thick-film electrode arrays are an attractive tool that may be implemented for general tissue engineering and neuroscience research.
Implantable medical devices are increasingly being used to perform electrophysiological stimulation, thus calling for wireless implantable neural stimulators for which wireless power transfer is ...needed. Compared with radio frequency and inductive coupling wireless power transfer methods, acoustic wireless power transfer features lower attenuation, a smaller size and a higher safe power threshold. This paper demonstrates the design, fabrication, assembly and characterization of a mm-sized acoustic wireless implantable neural stimulator based on a piezoelectric micromachined ultrasound transducer. Ex vivo experiments in water are conducted to characterize the power transfer link, showing improvement of the power transfer efficiency by more than two times with a matching circuit. Following FDA guidelines, the wireless implantable neural stimulator achieves a 3.24 μW output power in tissue. The feasibility for rat sciatic nerve stimulation is successfully demonstrated in vivo by the implantable prototype with a size of 5 × 5.5 × 2.5 mm3. The proposed solution has the potential to shrink the entire implanted system to a monolithic transducer-IC chip, paving the way toward an acoustic wireless implantable neural stimulator with higher levels of biocompatibility, integration and miniaturization.
•The acoustic wireless implantable neural stimulator is tiny in size and biocompatible.•The stimulator is based on piezoelectric micromachined ultrasound transducers.•In vivo test shows successful and repeatable sciatic nerve stimulation of rats.•Sciatic nerve stimulation is confirmed by leg twitch and electromyography feedback.•The solution has the potential to shrink the entire system to a monolithic chip.
Tungsten microwires are commonly used in neuroscience for their high mechanical strength, flexibility, which allows tailoring them to brain and peripheral nerve implantations, and cost-effectiveness ...compared to other electrode materials. However, challenges such as high impedance and foreign body reactions limit their use as acute and chronic electrophysiology tools. In this work, we propose a novel method for successfully coating tungsten microwires with PEDOT (poly(3,4-ethylenedioxythiophene)) doped with perchlorate anions ClO
4
−
using electropolymerization. Pre-treatment of the microwires with annealing resulted in the formation of a WO
3
coating that facilitated the nucleation and deposition of PEDOT, which was more homogeneous than that on gold microwires under the same conditions.
In vitro
, PEDOT decreased the impedance and increased the capacitance compared to bare tungsten microwires.
In vivo
, the PEDOT coating enhanced the signal-to-noise ratio and reduced the standard deviation of noise in acute preliminary electrophysiology recordings of spontaneous activity in the brain and evoked activity in the sciatic nerve of the rat.
A novel simple and inexpensive methodology based on electrodeposition of PEDOT is presented to improve the properties of tungsten microwires, making them a safe and accessible tool in electrophysiology studies.
Tungsten microwires are commonly used in neuroscience for their high mechanical strength, flexibility, which allows tailoring them to brain and peripheral nerve implantations, and cost-effectiveness ...compared to other electrode materials. However, challenges such as high impedance and foreign body reactions limit their use as acute and chronic electrophysiology tools. In this work, we propose a novel method for successfully coating tungsten microwires with PEDOT (poly(3,4-ethylenedioxythiophene)) doped with perchlorate anions ClO
4
−
using electropolymerization. Pre-treatment of the microwires with annealing resulted in the formation of a WO
3
coating that facilitated the nucleation and deposition of PEDOT, which was more homogeneous than that on gold microwires under the same conditions.
In vitro
, PEDOT decreased the impedance and increased the capacitance compared to bare tungsten microwires.
In vivo
, the PEDOT coating enhanced the signal-to-noise ratio and reduced the standard deviation of noise in acute preliminary electrophysiology recordings of spontaneous activity in the brain and evoked activity in the sciatic nerve of the rat.
The development of neural interfaces with superior biocompatibility and improved tissue integration is vital for treating and restoring neurological functions in the nervous system. A critical factor ...is to increase the resolution for mapping neuronal inputs onto implants. For this purpose, we have developed a new category of neural interface comprising induced pluripotent stem cell (iPSC)-derived myocytes as biological targets for peripheral nerve inputs that are grafted onto a flexible electrode arrays. We show long-term survival and functional integration of a biohybrid device carrying human iPSC-derived cells with the forearm nerve bundle of freely moving rats, following 4 weeks of implantation. By improving the tissue-electronics interface with an intermediate cell layer, we have demonstrated enhanced resolution and electrical recording in vivo as a first step toward restorative therapies using regenerative bioelectronics.
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