Conductive polymers are of great interest in the field of neural electrodes because of their potential to improve the interfacial properties of electrodes. In particular, the conductive polymer poly (3,4)-ethylenedioxithiophene (PEDOT) has been widely studied for neural applications. Objective: This review compares methods for electrodeposition of PEDOT on metal neural electrodes, and analyses the effects of deposition methods on morphology and electrochemical performance. Approach: Electrochemical performances were analysed against several deposition method choices, including deposition charge density and co-ion, and correlations were explained to morphological and structural arguments as well as characterisation methods choices. Main results: Coating thickness and charge storage capacity are positively correlated with PEDOT electrodeposition charge density. We also show that PEDOT coated electrode impedance at 1 kHz, the only consistently reported impedance quantity, is strongly dependent upon electrode radius across a wide range of studies, because PEDOT coatings reduces the reactance of the complex impedance, conferring a more resistive behaviour to electrodes (at 1 kHz) dominated by the solution resistance and electrode geometry. This review also summarises how PEDOT co-ion choice affects coating structure and morphology and shows that co-ions notably influence the charge injection limit but have a limited influence on charge storage capacity and impedance. Finally we discuss the possible influence of characterisation methods to assess the robustness of comparisons between published results using different methods of characterisation. Significance: This review aims to serve as a common basis for researchers working with PEDOT by showing the effects of deposition methods on electrochemical performance, and aims to set a standard for accurate and uniform reporting of methods.

With the ageing population, musculoskeletal conditions are becoming more inherent. Delayed union is defined as a slower than normal fracture healing response, with no healing after 4 to 6 months; however, the union is anticipated given sufficient time. In the context of delayed/non-union, fragility fractures in osteoporotic populations carry significant patient morbidity and socioeconomic costs. Multiple mechanisms hinder fracture healing in osteoporotic patients, imbalanced bone remodelling leads to impaired bone microarchitecture due to reduced osteoblast number and activity and as such, callus formation is diminished. Since stem cells can self-renew and differentiate into various tissue lineages, they are becoming very popular in tissue regeneration in musculoskeletal conditions. In this review, we discuss the role of stem cells in physiological fracture healing and their potential therapeutic use following a fracture. We explore the potential of stem cells, the release of chemokines and cytokines to reduce fracture risk in osteoporosis.

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. 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. 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. 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.

This paper presents a fully implantable closed-loop device for use in freely moving rodents to investigate new treatments for motor neuron disease. The 0.18 µm CMOS integrated circuit comprises 4 stimulators, each featuring 16 channels for optical and electrical stimulation using arbitrary current waveforms at frequencies from 1.5 Hz to 50 kHz, and a bandwidth programmable front-end for neural recording. The implant uses a Qi wireless inductive link which can deliver >100 mW power at a maximum distance of 2 cm for a freely moving rodent. A backup rechargeable battery can support 10 mA continuous stimulation currents for 2.5 hours in the absence of an inductive power link. The implant is controlled by a graphic user interface with broad programmable parameters via a Bluetooth low energy bidirectional data telemetry link. The encapsulated implant is 40 mm × 20 mm × 10 mm. Measured results are presented showing the electrical performance of the electronics and the packaging method.

Infection is the primary failure modality for transcutaneous implants because the skin breach provides a route for pathogens to enter the body. Intraosseous transcutaneous amputation prostheses (ITAP) are being developed to overcome this problem by creating a seal at the skin-implant interface. Oral gingival epithelial cell attachment creates an infection-free seal around dental implants. However, this has yet to be achieved consistently outside of the oral environment. Epithelial cells attach to metal substrates by means of hemidesmosomes and focal adhesions. Their density per unit cell is an indicator of attachment strength. We postulate that gingival epithelial cells express more hemidesmosomes and focal adhesions at earlier time points, compared with epidermal keratinocytes, and this increased speed and strength of attachment may be the reason why an infection-free seal is often achieved around dental implants but less frequently around ITAP. The aim of this study was to compare epidermal keratinocyte with oral gingival cell attachment on titanium alloy in vitro, to determine whether these two cell types differ in their speed and strength of attachment. We aimed to test the hypothesis that gingival cells up-regulate focal adhesion and hemidesmosome formation at earlier time points compared with extra-oral keratinocytes. To test this hypothesis we cultured epidermal keratinocytes and oral gingival cells on titanium alloy substrates and assessed cell attachment by focal adhesions and hemidesmosome expression at 4, 24, 48 and 72 hours. Formation and expression of hemidesmosomes temporally lagged behind that of focal adhesions in both cell types. Gingival derived cells up-regulated focal adhesion and hemidesmosome expression at earlier time points compared with epidermal keratinocytes. Hemidesmosome expression in oral gingival cells was 3 times greater compared with epidermal keratinocytes at 4 hours. Our findings indicate that earlier attachment may be key to the success of the dental implant transcutaneous interface.

The use of a bone-anchored device to transmit electrical signals from internalized muscle electrodes was studied in a sheep model. The bone-anchored device was used as a conduit for the passage of a wire connecting an internal epimysial electrode to an external signal-recording device. The bone-anchored device was inserted into an intact tibia and the electrode attached to the adjacent M. peroneus tertius. “Physiological” signals with low signal-to-noise ratios were successfully obtained over a 12-week period by walking the sheep on a treadmill. Reliable transmission of multiple muscle signals across the skin barrier is essential for providing intuitive, biomimetic upper limb prostheses. This technology has the potential to provide a better functional and reliable solution for upper limb amputee rehabilitation: attachment and control.