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.

Abstract-The use of a bone-anchored device to transmit electrical signals from internalised 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 boneanchored 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.

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 skinimplant 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.

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.

Selective MNIs with the peripheral nervous system may allow upper limb amputees to control prostheses intuitively.

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. This review compares methods for electrodeposition of PEDOT on metal neural electrodes, and analyses the effects of deposition methods on morphology and electrochemical performance. The findings of this review show that: 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 behavior 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.

This paper presents an active microchannel neural interface (MNI) using seven stacked application specific integrated circuits (ASICs). The approach provides a solution to the present problem of interconnect density in three-dimensional (3-D) MNIs. The 4 mm 2 ASIC is implemented in 0.35 µm high-voltage CMOS technology. Each ASIC is the base for seven microchannels each with three electrodes in a pseudo-tripolar arrangement. Multiplexing allows stimulating or recording from any one of 49 channels, across seven ASICs. Connections to the ASICs are made with a fiveline parallel bus. Current controlled biphasic stimulation from 5 to 500 µA has been demonstrated with switching between channels and ASICs. The high-voltage technology gives a compliance of 40 V for stimulation, appropriate for the high impedances within microchannels. High frequency biphasic stimulation, up to 40 kHz is achieved, suitable for reversible high frequency nerve blockades. Recording has been demonstrated with mV level signals; commonmode inputs are differentially distorted and limit the CMRR to 40 dB. The ASIC has been used in vitro in conjunction with an oversize (2 mm diameter) microchannel in phosphate buffered saline, demonstrating attenuation of interference from outside the microchannel and tripolar recording of signals from within the microchannel. By using five-lines for 49 active microchannels the device overcomes limitations when connecting many electrodes in a 3-D miniaturized nerve interface.

This article presents a versatile neurostimulation platform featuring a fully implantable multi-channel neural stimulator for chronic experimental studies with freely moving large animal models involving peripheral nerves. The implant is hermetically sealed in a ceramic enclosure and encapsulated in medical grade silicone rubber, and then underwent active tests at accelerated aging conditions at 100°C for 15 consecutive days. The stimulator microelectronics are implemented in a 0.6-μm CMOS technology, with a crosstalk reduction scheme to minimize cross-channel interference, and high-speed power and data telemetry for battery-less operation. A wearable transmitter equipped with a Bluetooth Low Energy radio link, and a custom graphical user interface provide real-time, remotely controlled stimulation. Three parallel stimulators provide independent stimulation on three channels, where each stimulator supports six stimulating sites and two return sites through multiplexing, hence the implant can facilitate stimulation at up to 36 different electrode pairs. The design of the electronics, method of hermetic packaging and electrical performance as well as in vitro testing with electrodes in saline are presented.