Advanced Materials in Wireless, Implantable Electrical Stimulators that Offer Rapid Rates of Bioresorption for Peripheral Axon Regeneration

Abstract

Injured peripheral nerves typically exhibit unsatisfactory and incomplete functional outcomes, and there are no clinically approved therapies for improving regeneration. Post-operative electrical stimulation (ES) increases axon regrowth, but practical challenges, from the cost of extended operating room time to the risks and pitfalls associated with transcutaneous wire placement, have prevented broad clinical adoption. This study presents a possible solution in the form of advanced bioresorbable materials for a type of thin, flexible, wireless implant that provides precisely controlled ES of the injured nerve for a brief time in the immediate post-operative period. Afterward, rapid, complete, and safe modes of bioresorption naturally and quickly eliminate all of the constituent materials in their entirety, without the need for surgical extraction. The unusually high rate of bioresorption follows from the use of a unique, bilayer enclosure that combines two distinct formulations of a biocompatible form of polyanhydride as an encapsulating structure, to accelerate the resorption of active components and confine fragments until complete resorption. Results from mouse models of tibial nerve transection with re-anastomosis indicate that this system offers levels of performance and efficacy that match those of conventional wired stimulators, but without the need to extend the operative period or to extract the device hardware.

Implantation and Control of Wireless, Battery-free Systems for Peripheral Nerve Interfacing

“…In the sciatic nerve injury model, the implant is placed around the right sciatic nerve prior to end-to-end repair of the tibial nerve branch (Figure 3 of the CMAP from wire-based nerve stimulation 21 , well above the threshold required for therapeutic effects in clinical studies 6 , 7 , 8 , 9 . In the example shown, the longer latency of the wireless stimulator vs. wired stimulator was due to its greater distance from the recorded muscle.…”

“…We demonstrate how this novel class of biomedical implants can be used to deliver a therapeutic electrical stimulation paradigm shown to enhance axon regeneration in preclinical and clinical studies (for review, see 22 ). This protocol is uncomplicated and can be extrapolated to smaller animal models, such as mice 21 , as well as other wireless, battery-free, and fully implantable devices with functionality that includes optoelectronic and microfluidic peripheral nerve interfaces 18 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 . Also demonstrated is the approach using the rodent sciatic nerve, which is the most common experimental model 31 .…”

“…NOTE: Examining the recruitment of peripheral axons and induction of axonal regeneration by monophasic and biphasic stimuli, prior studies reported a negligible effect due to the differences in waveform characteristic 20 , and this group has been able to achieve therapeutic electrical stimulation enhancement with the same monophasic current parameters in mice 21 and rats 18 . Furthermore, prior studies examined biocompatibility in vivo and in vitro and did not find any evidence of tissue damage from heating effects or the materials themselves.…”

Physical Stimulation Combined with Biomaterials Promotes Peripheral Nerve Injury Repair

“…To solve this problem, scholars further developed absorbable nerve electrodes. Guo et al fabricated a bilayer biocompatible, wireless bioabsorbable nerve stimulator [ 47 ]. The study found that the device could operate stably in mice for 5 h, meeting the 1-h E.S.…”

Highly Sensitive Flexible Temperature Sensor Made Using PEDOT:PSS/PANI

“…Rigid equipment lacks flexibility, limiting the application of temperature sensors on complicated surfaces such as aircraft engines . To address this limitation, researchers have developed flexible temperature devices, which can be smoothly attached to a measured object’s surface and can monitor temperature continuously. ,− In addition, flexible temperature sensors could potentially play an essential role in personal health care and disease diagnosis in the near future. ,,− Sensors that have high sensitivity, fast response times, and high repeatability are in demand. ,,, …”