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Printable microscale interfaces for long-term peripheral nerve mapping and precision control.

ABSTRACT: The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying peripheral interfacing technologies. Here, we present a microscale implantable device - the nanoclip - for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high signal-to-noise ratio recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation within the confines of the small device can achieve multi-dimensional control of a small nerve. These results highlight the potential of new microscale design and fabrication techniques for realizing viable devices for long-term peripheral interfacing.

SUBMITTER: Otchy TM

PROVIDER: S-EPMC7442820 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Printable microscale interfaces for long-term peripheral nerve mapping and precision control.

Otchy Timothy M TM Michas Christos C Lee Blaire B Gopalan Krithi K Nerurkar Vidisha V Gleick Jeremy J Semu Dawit D Darkwa Louis L Holinski Bradley J BJ Chew Daniel J DJ White Alice E AE Gardner Timothy J TJ

Nature communications 20200821 1

The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying peripheral interfacing technologies. Here, we present a ...[more]

PMID: 32826892

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Project description:Introduction: Man-machine interfacing remains the main challenge for accurate and reliable control of bionic prostheses. Implantable electrodes in nerves and muscles may overcome some of the limitations by significantly increasing the interface's reliability and bandwidth. Before human application, experimental preclinical testing is essential to assess chronic in-vivo biocompatibility and functionality. Here, we analyze available animal models, their costs and ethical challenges in special regards to simulating a potentially life-long application in a short period of time and in non-biped animals. Methods: We performed a literature analysis following the PRISMA guidelines including all animal models used to record neural or muscular activity via implantable electrodes, evaluating animal models, group size, duration, origin of publication as well as type of interface. Furthermore, behavioral, ethical, and economic considerations of these models were analyzed. Additionally, we discuss experience and surgical approaches with rat, sheep, and primate models and an approach for international standardized testing. Results: Overall, 343 studies matched the search terms, dominantly originating from the US (55%) and Europe (34%), using mainly small animal models (rat: 40%). Electrode placement was dominantly neural (77%) compared to muscular (23%). Large animal models had a mean duration of 135 ± 87.2 days, with a mean of 5.3 ± 3.4 animals per trial. Small animal models had a mean duration of 85 ± 11.2 days, with a mean of 12.4 ± 1.7 animals. Discussion: Only 37% animal models were by definition chronic tests (>3 months) and thus potentially provide information on long-term performance. Costs for large animals were up to 45 times higher than small animals. However, costs are relatively small compared to complication costs in human long-term applications. Overall, we believe a combination of small animals for preliminary primary electrode testing and large animals to investigate long-term biocompatibility, impedance, and tissue regeneration parameters provides sufficient data to ensure long-term human applications.

Project description:BackgroundOnabotulinumtoxin A (BOTOX) is an FDA-approved treatment for chronic migraine headaches (MHs) that involves on-label, high-dose administration across 31 anatomic sites. Anatomically specific peripheral nerve trigger sites have been identified that contribute to MH pathogenesis and are amenable to both BOTOX injection and surgical decompression. These sites do not always correlate with the on-label FDA-approved injection pattern, but represent a more targeted approach. The efficacy of peripheral nerve-directed BOTOX injection as an independent long-term therapeutic option has not been investigated.MethodsThe technique for peripheral nerve-directed therapeutic long-term BOTOX injection is described. A retrospective review was subsequently completed for 223 patients with MH. Sixty-six patients elected to proceed with diagnostic BOTOX injections. Of these, 24 continued long-term therapeutic BOTOX injections, whereas 42 matriculated to surgery. Outcomes were tracked.ResultsInitial outcomes included significant improvement in migraine headache index (MHI) (53.5 ± 83.0, P < 0.006), headache days/mo (9.2 ± 12.7, P < 0.0009), and migraine severity (2.6 ± 2.5, P < 0.00008) versus baseline. MHI improved from the initiation of diagnostic injections to the establishment of steady-state injections (P < 0.002), and further improved over time (P < 0.05, mean follow-up 615 days) with no desensitization observed. Decompressive surgery resulted in significant improvement in MHI (100.8 ± 109.7, P < 0.0000005), headache days/mo (10.8 ± 12.7, P < 0.000002), migraine severity (3.0 ± 3.8, P < 0.00001), and migraine duration in hours (16.8 ± 21.6, P < 0.0007). MHI improvement with surgery was better than long-term BOTOX injections (P < 0.05).ConclusionsThough inferior to surgical decompression, preliminary data demonstrate that targeted peripheral nerve-directed BOTOX injection is an effective primary therapy for MH representing a possible alternative to nondirected BOTOX injection with decreased dosage requirements and potentially decreased cost.

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Printable microscale interfaces for long-term peripheral nerve mapping and precision control.

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Printable microscale interfaces for long-term peripheral nerve mapping and precision control.

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