Electronic dura mater for long-term multimodal neural interfaces

Abstract

Abstract:We introduce a new class of neural implants with the topology and compliance of dura mater, the protective membrane of the brain and spinal cord. These neural interfaces, which we called e-dura, achieve chronic bio-integration within the subdural space where they conform to the statics and dynamics of neural tissue. e-dura embeds interconnects, electrodes and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. e-dura extracted cortical states in freely behaving animals for brain machine interface, and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury. e-dura offers a novel platform for chronic multimodal neural interfaces in basic research and neuroprosthetics.3 Neuroprosthetic medicine is improving the lives of countless individuals. Cochlear implants restore hearing in deaf children, deep brain stimulation alleviates Parkinsonian symptoms, and spinal cord neuromodulation attenuates chronic neuropathic pain (1). These interventions rely on implants developed in the 1980s (2, 3). Since then, advances in electroceutical, pharmaceutical, and more recently optogenetic treatments triggered development of myriad neural interfaces that combine multiple modalities (4-9). However, the conversion of these sophisticated technologies into chronic implants mediating long-lasting functional benefits has yet to be achieved. A recurring challenge restricting chronic bio-integration is the substantial biomechanical mismatch between implants and neural tissues (10-13). Here, we introduce a new class of soft multimodal neural interfaces that achieve chronic bio-integration, and we demonstrate their long-term efficacy in clinically relevant applications. e-dura fabrication. We designed and engineered soft interfaces that mimic the topology and mechanical behavior of the dura mater (Fig. 1A-B). The implant, which we called electronic dura mater or e-dura, integrates a transparent silicone substrate (120µm in thickness), stretchable gold interconnects (35nm in thickness), soft electrodes coated with a novel platinum-silicone composite (300µm in diameter), and a compliant fluidic microchannel (100µm x 50µm in crosssection) (Fig. 1C-D, fig. S1-S2-S3). The interconnects and electrodes transmit electrical excitation and transfer electrophysiological signals.The microfluidic channel, termed chemotrode (14), delivers drugs locally (Fig. 1C, fig. S3). Microcracks in the gold interconnects (15) and the newly developed soft platinum-silicone composite electrodes confer exceptional stretchability to the entire implant (Fig. 1B, Movie S1). The patterning techniques of metallization and microfluidics support rapid manufacturing of customized neuroprostheses.4 e-dura implantation. Most implants used experimentally or clinically to assess and treat neurological disorders are placed above the dura mater (3,(16)(17)(18). The compliance of e-...

3D Printing of Transparent and Conductive Heterogeneous Hydrogel–Elastomer Systems

“…[5][6][7][8] Although many stretchable conductors exist, including liquid metals, [9,10] nanowires, [11,12] nanoribbons [13] , pre-stretched elastomer fibers with conductive coatings, [14] and micro-cracked metals, [15,16] these materials have generally been unable to achieve high levels of optical transparency while maintaining high conductivities and stretchability; a feature that would enable their use in optogenetics [17] or allow optical imaging of the underlying substrate. Conventional strategies of incorporating metallic components with elastomers to attain stretchability also yield non-trivial failure modes such as liquid metal leakage [8] and hard-soft material interfacial failure [18] .…”

Toward Bioelectronic Medicine—Neuromodulation of Small Peripheral Nerves Using Flexible Neural Clip

“…The pelvic nerve is a promising stimulation target for the control of bladder function as it provides autonomic efferent inputs to contract the bladder detrusor muscle, and is anatomically and functionally more specific for bladder neuromodulation 19, 28, 29. However, the pelvic nerve is a small visceral nerve located deep within the body, which leads to difficulties in implantation, as well as maintaining contact for reliable stimulation if current neural electrodes are used 6, 12, 13, 30. We successfully performed stimulation of the pelvic nerves using a miniature FNC to control bladder function while monitoring bladder pressure ( Figure 3 a).…”

“…In case of NIT in the CNS applications, glial scar‐free neural recordings have been achieved using ultraflexible probes in the brains of rodents 10. Furthermore, the brain–spine interface was able to support the locomotion of monkeys using a multimodal neural interface, called e‐dura 11, 12…”

Blending Electronics with the Human Body: A Pathway toward a Cybernetic Future

“…In a recent cutting‐edge study by a group of scientists from École Polytechnique Fédérale de Lausanne (EPFL), this daunting challenge was addressed by embedding flexible Pt electrodes and interconnects within a soft and biocompatible silicone‐based substrate, which they coined electronic dura matter or simply “e‐Dura” ( Figure 13 ). 15 The e‐dura implant is composed of a highly elastic silicone substrate measuring 120 µm in thickness, stretchable Au interconnects (35 nm in thickness) and soft electrodes coated with a Pt–silicone composite (300 mm in diameter), which altogether enable the device to mediate electrical stimulation and transfer electrophysiological signals from the spinal cord tissue to a microcomputed tomography (CT) scanner for assessment of whole‐body movements during daily activities. As a new feature, a microfluidic‐based delivery system (100 mm × 50 mm in cross‐section) was incorporated into e‐Dura for controlled delivery of various chemical substances to the injury site.…”