Abstract
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.
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Acknowledgements
The authors would like to acknowledge Dr. Aaron Hucekly for assistance with some of the surgical procedures; Katie-Marie Buswell-Zuk and Ryan Edgar, and Katie Rousu for surgical monitoring and maintenance of anesthesia at the Ray Rajotte Surgical Medical Research Institute; Peter Seres for MRI scans; David Roszko, Michel Gautier and Rod Gramlich for technical assistance with electromechanical devices; and Dr. Leanne Paetkau, Dr. Nathan Bosvik and Isabelle Gauthier for veterinary support.
Funding
This work was funded in part by the US Department of Defense Congressionally-directed Medical Research Program—Spinal Cord Injury Research Program, Canadian Institutes of Health Research, Canada Foundation for Innovation, Prairies Economic Development Canada, University of Alberta Hospital Foundation, and Brain Canada Foundation. SM was supported by a Faculty of Medicine and Dentistry Dean’s Doctoral Scholarship, a 75th Anniversary Scholarship, an Alberta Graduate Excellence Studentship and an Alberta Innovates Graduate Studentship. CLO was supported by an Alberta Graduate Excellence Studentship and a Natural Science and Engineering Research Council Graduate Scholarship. AA was supported by a 75th Anniversary Faculty of Medicine and Dentistry Graduate Student Award and a Mary Louise Imrie Graduate Student Award. VKM is a Canada Research Chair (Tier 1) in Functional Restoration.
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V.K.M. conceived the experiments and secured funding. S.M. implemented the experiments, collected data, and wrote the first version of the manuscript. C.L.O. assisted with the experiments and led the immunohistochemistry work. A.A. assisted with the experiments and analyzed the range of movement and isometric force data. N.T. contributed to all experiments, assisted with anesthesia monitoring, and participated in tissue processing for histology and immunohistochemistry. K.S. assisted with the experiments and tissue processing. D.W. developed the bench testing setup for mechanical assessments. O.T. contributed to the development of the implantable stimulator. P.R.T. developed the implantable stimulator. R.F. performed the surgical procedures in most experiments. All authors reviewed the manuscript.
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Mirkiani, S., O’Sullivan, C.L., Arefadib, A. et al. A fully implantable intraspinal microstimulation device for early preclinical evaluation of feasibility, stability, and functionality. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42212-9
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DOI: https://doi.org/10.1038/s41598-026-42212-9


