Thin-Film Peripheral Nerve Cuffs for Chronic High-Resolution Interfacing and Long-Term Stability

Peripheral nerve implants hold great potential for the development of treatments for a wide range of clinical conditions. Whether by recording electrical activity carried by nerves, or influencing it through electrical stimulation, implantable devices interfacing with the nerves of the body can modulate or gather information on the state of organs or structures to which any nerve connects. As individual nerves often connect to multiple target structures, such as multiple muscles or large areas of skin, devices containing high density arrays of electrodes to selectively record from distinct bundles of axons within individual nerves have been a particularly promising area of research.<br/>High-resolution nerve interfacing is, however, limited by a major drawback: the breakdown of the tissue-implant interface due to the development of the foreign body reaction (FBR) between the two over long periods of time. High-resolution nerve implants typically have to be inserted into the nerve itself, leading to axon death as a consequence of direct damage from the implant and inflammation. Moreover, these devices are often made using stiff materials such as silicon, which cause further damage to tissue and worsen FBR.<br/>We aimed to produce a peripheral nerve implant capable of high-resolution recording and stimulation while also improving tissue compatibility. Our devices are microfabricated using thin-film technology, and are composed of gold tracks insulated between two layers of parylene-C, forming a flexible sheet. The tracks terminate in high-density poly(ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)-based electrode arrays. The device is patterned into three sheets, each containing 9 to 12 electrodes 100x100 μm in size, with the sheets being able to be rolled into cuffs. This design allows our device to simultaneously cuff around three nerves, forming high-resolution interfaces around these for both stimulation and recording of sub-nerve compartments. By both using a flexible architecture and a non-penetrating cuff design, our implants are designed to minimize FBR and improve long-term tissue compatibility.<br/>To validate their function, we implant these devices into the ulnar, radial and median nerves controlling arm function in rat models, and show their ability to record nerve action potentials and stimulate muscle contraction. We further show that our thin-film cuffs exhibit good long-term tissue compatibility, exhibiting lower FBR and nerve damage than control materials commonly used in nerve cuffs (PDMS) when chronically implanted for four weeks. Finally, we implant the cuffs into the forearm nerves of rats trained to reach out and grasp sugar pellets, and route the connections of the cuffs subcutaneously to externalize them through a headcap. We demonstrate the ability of our device to perform in chronic implantation scenarios by recording sensorimotor nerve activity in chronically-implanted awake animals performing skilled behavioural grasping tasks.