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<p>Electrical stimulation of the spinal cord has shown promise in restoring standing and walking after paralysis, yet key challenges remain in achieving selective and stable movements over long durations of stimulation. Intraspinal microstimulation (ISMS) provides precise and sustained activation of motor circuits in animal models. Nevertheless, translation of ISMS to humans requires assessment of surgical feasibility, safety and long-term stability in an animal model with spine and spinal cord size and morphology similar to those in humans. Here, we demonstrate the development and implementation of a fully implantable, wirelessly controlled ISMS device as well as its feasibility of implantation and functionality in domestic pigs. The ISMS implants contained strain relief mechanisms to improve mechanical compliance and minimize foreign body response. We tested the device in 4 pigs for periods of 8 to 14&#xa0;days to assess surgical feasibility and early implant stability. Following implantation, stimulation through the electrodes successfully generated functional muscle contractions, graded movements around the hip, knee, and ankle joints. Post-mortem magnetic resonance imaging of the spinal cord revealed that the electrodes remained in place. All animals implanted with the device experienced transient motor paralysis post-implantation, with recovery of muscle strength and coordination after one week. Immunohistochemical analysis revealed that glial encapsulation around the electrodes was confined to a 200&#xa0;µm region from the center of the implantation sites and showed no migration of the implant. This suggests that the transient deficits are likely the effects of the surgical procedure (laminectomy, durotomy and spinal cord manipulation), although a contribution from the penetrating electrodes cannot be excluded. Such complications can be minimized by optimized surgical protocols, particularly, the application of anti-inflammatory corticosteroids and epidural hemostatic agents. This work establishes the feasibility of ISMS for restoring standing and walking after spinal cord injury and demonstrates its capability of selectively targeting motor networks throughout the lumbar enlargement in a large-animal model.</p>

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A fully implantable intraspinal microstimulation device for early preclinical evaluation of feasibility, stability, and functionality

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月24日

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  • Soroush Mirkiani,
  • Carly L. O’Sullivan,
  • Amin Arefadib,
  • Neil Tyreman,
  • Katalin Sari,
  • Don Wilson,
  • Omar Tawakol,
  • Philip R. Troyk,
  • Richard Fox,
  • Vivian K. Mushahwar

摘要

Electrical stimulation of the spinal cord has shown promise in restoring standing and walking after paralysis, yet key challenges remain in achieving selective and stable movements over long durations of stimulation. Intraspinal microstimulation (ISMS) provides precise and sustained activation of motor circuits in animal models. Nevertheless, translation of ISMS to humans requires assessment of surgical feasibility, safety and long-term stability in an animal model with spine and spinal cord size and morphology similar to those in humans. Here, we demonstrate the development and implementation of a fully implantable, wirelessly controlled ISMS device as well as its feasibility of implantation and functionality in domestic pigs. The ISMS implants contained strain relief mechanisms to improve mechanical compliance and minimize foreign body response. We tested the device in 4 pigs for periods of 8 to 14 days to assess surgical feasibility and early implant stability. Following implantation, stimulation through the electrodes successfully generated functional muscle contractions, graded movements around the hip, knee, and ankle joints. Post-mortem magnetic resonance imaging of the spinal cord revealed that the electrodes remained in place. All animals implanted with the device experienced transient motor paralysis post-implantation, with recovery of muscle strength and coordination after one week. Immunohistochemical analysis revealed that glial encapsulation around the electrodes was confined to a 200 µm region from the center of the implantation sites and showed no migration of the implant. This suggests that the transient deficits are likely the effects of the surgical procedure (laminectomy, durotomy and spinal cord manipulation), although a contribution from the penetrating electrodes cannot be excluded. Such complications can be minimized by optimized surgical protocols, particularly, the application of anti-inflammatory corticosteroids and epidural hemostatic agents. This work establishes the feasibility of ISMS for restoring standing and walking after spinal cord injury and demonstrates its capability of selectively targeting motor networks throughout the lumbar enlargement in a large-animal model.