All-Polymer Printed Low-Cost Regenerative Nerve Cuff Electrodes

Abstract

Neural regeneration after lesions is still limited by several factors and new technologies are developed to address this issue. Here, we present and test in animal models a new regenerative nerve cuff electrode (RnCE). It is based on a novel low-cost fabrication strategy, called “Print and Shrink”, which combines the inkjet printing of a conducting polymer with a heat-shrinkable polymer substrate for the development of a bioelectronic interface. This method allows to produce miniaturized regenerative cuff electrodes without the use of cleanroom facilities and vacuum based deposition methods, thus highly reducing the production costs. To fully proof the electrodes performance in vivo we assessed functional recovery and adequacy to support axonal regeneration after section of rat sciatic nerves and repair with RnCE. We investigated the possibility to stimulate the nerve to activate different muscles, both in acute and chronic scenarios. Three months after implantation, RnCEs were able to stimulate regenerated motor axons and induce a muscular response. The capability to produce fully-transparent nerve interfaces provided with polymeric microelectrodes through a cost-effective manufacturing process is an unexplored approach in neuroprosthesis field. Our findings pave the way to the development of new and more usable technologies for nerve regeneration and neuromodulation.

In Vivo Organic Bioelectronics for Neuromodulation

“…Flexibility also allows for the development of nonplanar device geometries for various applications. Ferrari et al combined ink jet printing of PEDOT:PSS with a heat-shrinkable polymer substrate to form cuff electrodes for nerve regeneration applications . The device was able to stimulate regenerated motor axons to induce a muscular response 3 months after implantation.…”

“…Ferrari et al combined ink jet printing of PEDOT:PSS with a heat-shrinkable polymer substrate to form cuff electrodes for nerve regeneration applications. 141 The device was able to stimulate regenerated motor axons to induce a muscular response 3 months after implantation. In another approach, Tian et al used the flexibility of their parylene C–PEDOT:PSS microelectrodes to create a flexible tubular electrode with drug delivery capability.…”

Neural repair and regeneration interfaces: a comprehensive review

“…This innovative approach has facilitated long-term implantation throughout the entire lifespan of a mouse, with no discernable tissue damage [112] (figure 4(b)). Inkjet printers can directly pattern polymer substrates into neural regeneration cuff electrodes with PEDOT: PSS and heat-shrinkable polymers to regenerate motor axons and incite muscle responses three months postimplantation [116]. A miniaturized, wireless, and bioresorbable electrotherapy system has been demonstrated to effectively accelerate wound closure, particularly in chronic cases associated with diabetes, by guiding epithelial migration, modulating inflammation, and promoting vasculogenesis, offering a practical solution for electrical stimulation therapy [6].…”

Recent Advances in Decellularized Matrix-Derived Materials for Bioink and 3D Bioprinting

“…In rat models of chronic and acute nerve injury, the fabricated RnCE has been shown to heal sciatic nerve injuries. However, the unique regenerative PNI microelectrode sequence showed that the long-term implantation of this electrode could be harmful [ 104 ].…”