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A fully implantable intraspinal microstimulation device for early preclinical evaluation of feasibility, stability, and functionality
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  • Published: 24 March 2026

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

  • Soroush Mirkiani1,2,
  • Carly L. O’Sullivan1,2,
  • Amin Arefadib1,2,
  • Neil Tyreman2,3,
  • Katalin Sari2,3,
  • Don Wilson2,3,
  • Omar Tawakol2,4,
  • Philip R. Troyk2,4,
  • Richard Fox2,5 &
  • …
  • Vivian K. Mushahwar1,2,3 

Scientific Reports , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Biotechnology
  • Engineering
  • Medical research
  • Neuroscience

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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Data availability

Data are provided within the manuscript.

References

  1. Ding, W. et al. Spinal cord injury: The global incidence, prevalence, and disability from the global burden of disease study 2019. Spine 47, 1532–1540 (2022).

    Google Scholar 

  2. Lu, Y. et al. Global incidence and characteristics of spinal cord injury since 2000–2021: A systematic review and meta-analysis. BMC Med. 22, 285 (2024).

    Google Scholar 

  3. National Spinal Cord Injury Statistical Center. Traumatic spinal cord injury facts and figures at a glance. Birmingham, AL: University of Alabama at Birmingham https://msktc.org/sites/default/files/Facts-and-Figures-2024-Eng-508.pdf (2024).

  4. Dimitrijevic, M. R., Gerasimenko, Y. & Pinter, M. M. Evidence for a spinal central pattern generator in humans a. Ann. N. Y. Acad. Sci. 860, 360–376 (1998).

    Google Scholar 

  5. Angeli, C. A. et al. Recovery of over-ground walking after chronic motor complete spinal cord injury. N. Engl. J. Med. 379, 1244–1250 (2018).

    Google Scholar 

  6. Harkema, S. et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: A case study. Lancet 377, 1938–1947 (2011).

    Google Scholar 

  7. Gill, M. L. et al. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat. Med. 24, 1677–1682 (2018).

    Google Scholar 

  8. Rowald, A. et al. Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis. Nat. Med. 28, 260–271 (2022).

    Google Scholar 

  9. Wagner, F. B. et al. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature 563, 65–71 (2018).

    Google Scholar 

  10. Mesbah, S. et al. Neuroanatomical mapping of the lumbosacral spinal cord in individuals with chronic spinal cord injury. Brain Commun. 5, fcac330 (2023).

    Google Scholar 

  11. Chalif, J. et al. Epidural spinal cord stimulation for spinal cord injury in humans: A systematic review. J. Clin. Med. 13, 1090 (2024).

    Google Scholar 

  12. Mushahwar, V. K. & Horch, K. W. Selective activation of muscle groups in the feline hindlimb through electrical microstimulation of the ventral lumbo-sacral spinal cord. IEEE Trans. Rehabil. Eng. 8, 11–21 (2000).

    Google Scholar 

  13. Bamford, J., Putman, C. & Mushahwar, V. Intraspinal microstimulation preferentially recruits fatigue-resistant muscle fibres and generates gradual force in rat. J. Physiol. 569, 873–884 (2005).

    Google Scholar 

  14. Saigal, R., Renzi, C. & Mushahwar, V. K. Intraspinal microstimulation generates functional movements after spinal-cord injury. IEEE. Trans. Neural Syst. Rehabil. Eng. 12, 430–440 (2004).

    Google Scholar 

  15. Holinski, B. et al. Intraspinal microstimulation produces over-ground walking in anesthetized cats. J. Neural Eng. 13, 056016 (2016).

    Google Scholar 

  16. Hachmann, J. T. et al. Large animal model for development of functional restoration paradigms using epidural and intraspinal stimulation. PLoS ONE 8, e81443 (2013).

    Google Scholar 

  17. Dalrymple, A. N. & Mushahwar, V. K. Intelligent control of a spinal prosthesis to restore walking after neural injury: Recent work and future possibilities. J. Med. Robot. Res. 5, 2041003 (2020).

    Google Scholar 

  18. Dalrymple, A. N., Roszko, D. A., Sutton, R. S. & Mushahwar, V. K. Pavlovian control of intraspinal microstimulation to produce over-ground walking. J. Neural Eng. 17, 036002 (2020).

    Google Scholar 

  19. Dalrymple, A. N., Everaert, D. G., Hu, D. S. & Mushahwar, V. K. A speed-adaptive intraspinal microstimulation controller to restore weight-bearing stepping in a spinal cord hemisection model. J. Neural Eng. 15, 056023 (2018).

    Google Scholar 

  20. Tawakol, O. et al. In-vivo testing of a novel wireless intraspinal microstimulation interface for restoration of motor function following spinal cord injury. Artif. Organs 48, 263–273 (2024).

    Google Scholar 

  21. Roszko, D. A. et al. Laser-microfabricated polymer multielectrodes for intraspinal microstimulation. IEEE Trans. Biomed. Eng. 70, 354–365 (2022).

    Google Scholar 

  22. Tawakol, O. S. M. S. A Wireless Intraspinal Microstimulation Interface for the Recovery of Motor Function Following Spinal Cord Injury. (Illinois: Illinois Institute of Technology, United States, 2024).

  23. Lau, B., Guevremont, L. & Mushahwar, V. K. Strategies for generating prolonged functional standing using intramuscular stimulation or intraspinal microstimulation. IEEE. Trans. Neural Syst. Rehabil. Eng. 15, 273–285 (2007).

    Google Scholar 

  24. Snow, S., Horch, K. W. & Mushahwar, V. K. Intraspinal microstimulation using cylindrical multielectrodes. IEEE Trans. Biomed. Eng. 53, 311–319 (2006).

    Google Scholar 

  25. Prochazka, A., Mushahwar, V. & Yakovenko, S. Activation and coordination of spinal motoneuron pools after spinal cord injury. Prog. Brain Res. 137, 109–124 (2002).

    Google Scholar 

  26. Guevremont, L. et al. Locomotor-related networks in the lumbosacral enlargement of the adult spinal cat: Activation through intraspinal microstimulation. IEEE Trans. Neural Syst. Rehabil. Eng. 14, 266–272 (2006).

    Google Scholar 

  27. Mushahwar, V., Aoyagi, Y., Stein, R. & Prochazka, A. Movements generated by intraspinal microstimulation in the intermediate gray matter of the anesthetized, decerebrate, and spinal cat. Can. J. Physiol. Pharmacol. 82, 702–714 (2004).

    Google Scholar 

  28. Zimmermann, J. B., Seki, K. & Jackson, A. Reanimating the arm and hand with intraspinal microstimulation. J. Neural Eng. 8, 054001 (2011).

    Google Scholar 

  29. Sharpe, A. N. & Jackson, A. Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord. J. Neural Eng. 11, 016005 (2014).

    Google Scholar 

  30. Tao, C. et al. Comparative study of intraspinal microstimulation and epidural spinal cord stimulation. in 3795–3798 (IEEE, 2019).

  31. Ibáñez, J., Angeli, C. A., Harkema, S. J., Farina, D. & Rejc, E. Recruitment order of motor neurons promoted by epidural stimulation in individuals with spinal cord injury. J. Appl. Physiol. 131, 1100–1110 (2021).

    Google Scholar 

  32. Gaunt, R. A., Prochazka, A., Mushahwar, V. K., Guevremont, L. & Ellaway, P. H. Intraspinal microstimulation excites multisegmental sensory afferents at lower stimulus levels than local α-motoneuron responses. J. Neurophysiol. 96, 2995–3005 (2006).

    Google Scholar 

  33. Mirkiani, S. et al. Functional motor mapping of domestic pig lumbar spinal cord using penetrating microelectrodes. J. Neuroeng. Rehabil. 22, 1–19 (2025).

    Google Scholar 

  34. Mushahwar, V. K., Collins, D. F. & Prochazka, A. Spinal cord microstimulation generates functional limb movements in chronically implanted cats. Exp. Neurol. 163, 422–429 (2000).

    Google Scholar 

  35. Bamford, J. A., Todd, K. G. & Mushahwar, V. K. The effects of intraspinal microstimulation on spinal cord tissue in the rat. Biomaterials 31, 5552–5563 (2010).

    Google Scholar 

  36. Ersen, A., Elkabes, S., Freedman, D. S. & Sahin, M. Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord. J. Neural Eng. 12, 016019 (2015).

    Google Scholar 

  37. Tsui, C. T., Lal, P., Fox, K. V., Churchward, M. A. & Todd, K. G. The effects of electrical stimulation on glial cell behaviour. BMC Biomed. Eng. 4, 7 (2022).

    Google Scholar 

  38. Polikov, V. S., Tresco, P. A. & Reichert, W. M. Response of brain tissue to chronically implanted neural electrodes. J. Neurosci. Methods. 148, 1–18 (2005).

    Google Scholar 

  39. Biran, R., Martin, D. C. & Tresco, P. A. Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays. Exp. Neurol. 195, 115–126 (2005).

    Google Scholar 

  40. Prasad, A. & Sanchez, J. C. Quantifying long-term microelectrode array functionality using chronic in vivo impedance testing. J. Neural Eng. 9, 026028 (2012).

    Google Scholar 

  41. McCreery, D., Pikov, V., Lossinsky, A., Bullara, L. & Agnew, W. Arrays for chronic functional microstimulation of the lumbosacral spinal cord. IEEE Trans. Neural Syst. Rehabil. Eng. 12, 195–207 (2004).

    Google Scholar 

  42. Toossi, A. et al. Comparative neuroanatomy of the lumbosacral spinal cord of the rat, cat, pig, monkey, and human. Sci. Rep. 11, 1955 (2021).

    Google Scholar 

  43. Toossi, A., Everaert, D. G., Azar, A., Dennison, C. R. & Mushahwar, V. K. Mechanically stable intraspinal microstimulation implants for human translation. Ann. Biomed. Eng. 45, 681–694 (2017).

    Google Scholar 

  44. Lee, J. H. et al. A novel porcine model of traumatic thoracic spinal cord injury. J. Neurotrauma 30, 142–159 (2013).

    Google Scholar 

  45. Zimmermann, J. B. & Jackson, A. Closed-loop control of spinal cord stimulation to restore hand function after paralysis. Front. Neurosci. 8, 87 (2014).

    Google Scholar 

  46. Toossi, A. et al. Effect of anesthesia on motor responses evoked by spinal neural prostheses during intraoperative procedures. J. Neural Eng. 16, 036003 (2019).

    Google Scholar 

  47. Toossi, A. et al. Ultrasound-guided spinal stereotactic system for intraspinal implants. J. Neurosurg. Spine 29, 292–305 (2018).

    Google Scholar 

  48. Mirkiani, S. et al. Safety of mapping the motor networks in the spinal cord using penetrating microelectrodes in Yucatan minipigs. J. Neurosurg. Spine. 1, 1–13 (2024).

    Google Scholar 

  49. Toossi, A., Everaert, D. G., Perlmutter, S. I. & Mushahwar, V. K. Functional organization of motor networks in the lumbosacral spinal cord of non-human primates. Sci. Rep. 9, 13539 (2019).

    Google Scholar 

  50. Borrell, J. A., Frost, S. B., Peterson, J. & Nudo, R. J. A 3D map of the hindlimb motor representation in the lumbar spinal cord in Sprague Dawley rats. J. Neural Eng. 14, 016007 (2016).

    Google Scholar 

  51. Krüger, J., Caruana, F. & Rizzolatti, G. Seven years of recording from monkey cortex with a chronically implanted multiple microelectrode. Front. Neuroeng. 3, 1314 (2010).

    Google Scholar 

  52. Wang, L. et al. High-density implantable neural electrodes and chips for massive neural recordings. Brain-X 2, e65 (2024).

    Google Scholar 

  53. Obaid, A. et al. Massively parallel microwire arrays integrated with CMOS chips for neural recording. Sci. Adv. 6, eaay2789 (2020).

    Google Scholar 

  54. Bamford, J. A., Lebel, R. M., Parseyan, K. & Mushahwar, V. K. The fabrication, implantation, and stability of intraspinal microwire arrays in the spinal cord of cat and rat. IEEE Trans. Neural Syst. Rehabil. Eng. 25, 287–296 (2016).

    Google Scholar 

  55. Cogan, S. F. Neural stimulation and recording electrodes. Annu. Rev. Biomed. Eng. 10, 275–309 (2008).

    Google Scholar 

  56. Kelly, A. et al. Laser-induced periodic surface structure enhances neuroelectrode charge transfer capabilities and modulates astrocyte function. ACS Biomater. Sci. Eng. 6, 1449–1461 (2020).

    Google Scholar 

  57. Pena, A. et al. Mechanical fatigue resistance of an implantable branched lead system for a distributed set of longitudinal intrafascicular electrodes. J. Neural Eng. 14, 066014 (2017).

    Google Scholar 

  58. Memberg, W. D., Stage, T. G. & Kirsch, R. F. A fully implanted intramuscular bipolar myoelectric signal recording electrode. Neuromodulation 17, 794–799 (2014).

    Google Scholar 

  59. Thota, A. K. et al. A Multi-lead Multi-electrode System for Neural-interface Enabled Advanced Prostheses. in 109–110 (IEEE, 2013).

  60. Thota, A. K., Jung, R. & Kuntaegowdanahalli, S. S. Multi-lead multi-electrode management system. (2016).

  61. Henderson, J. M., Schade, C., Sasaki, J., Caraway, D. L. & Oakley, J. C. Prevention of mechanical failures in implanted spinal cord stimulation systems. Neuromodulation 9, 183–191 (2006).

    Google Scholar 

  62. Shiroff, J. A., Skubitz, J. J. & Rawat, P. B. Electrode leads for use with implantable neuromuscular electrical stimulator. (2019).

  63. Machado, A. et al. Deep brain stimulation for Parkinson’s disease: Surgical technique and perioperative management. Mov. Disord. 21, S247–S258 (2006).

    Google Scholar 

  64. Hasoon, J. et al. Device-related complications associated with cylindrical lead spinal cord stimulator implants: A comprehensive review. Curr. Pain Headache Rep. 28, 941–947 (2024).

    Google Scholar 

  65. Dalrymple, A. N., Jones, S. T., Fallon, J. B., Shepherd, R. K. & Weber, D. J. Overcoming failure: Improving acceptance and success of implanted neural interfaces. Bioelectron. Med. 11, 6 (2025).

    Google Scholar 

  66. Huang, Y. et al. Crossed-wire laser microwelding of Pt-10 Pct Ir to 316 LVM stainless steel: Part II. Effect of orientation on joining mechanism. Metall. Mater. Trans. A 43, 1234–1243 (2012).

    Google Scholar 

  67. Quazi, M. M. et al. A comprehensive assessment of laser welding of biomedical devices and implant materials: recent research, development and applications. Crit. Rev. Solid State Mater. Sci. 46, 109–151 (2021).

    Google Scholar 

  68. Mirkiani, S. et al. Overground gait kinematics and muscle activation patterns in the Yucatan mini pig. J. Neural Eng. 19, 026009 (2022).

    Google Scholar 

  69. Lau, B., Guevremont, L. & Mushahwar, V. K. Strategies for generating prolonged functional standing using intramuscular stimulation or intraspinal microstimulation. IEEE Trans. Neural Syst. Rehabil. Eng. 15, 273–285 (2007).

    Google Scholar 

  70. Moritz, C. T., Lucas, T. H., Perlmutter, S. I. & Fetz, E. E. Forelimb movements and muscle responses evoked by microstimulation of cervical spinal cord in sedated monkeys. J. Neurophysiol. 97, 110–120 (2007).

    Google Scholar 

  71. Mushahwar, V. & Horch, K. Selective activation and graded recruitment of functional muscle groups through spinal cord stimulation. Ann. N. Y. Acad. Sci. 860, 531–535 (1998).

    Google Scholar 

  72. Gustafsson, B. & Jankowska, E. Direct and indirect activation of nerve cells by electrical pulses applied extracellularly. J. Physiol. 258, 33–61 (1976).

    Google Scholar 

  73. McIntyre, C. C. & Grill, W. M. Extracellular stimulation of central neurons: Influence of stimulus waveform and frequency on neuronal output. J. Neurophysiol. 88, 1592–1604 (2002).

    Google Scholar 

  74. Formento, E. et al. Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury. Nat. Neurosci. 21, 1728–1741 (2018).

    Google Scholar 

  75. Capogrosso, M. et al. A computational model for epidural electrical stimulation of spinal sensorimotor circuits. J. Neurosci. 33, 19326–19340 (2013).

    Google Scholar 

  76. Hachmann, J. T. et al. Epidural spinal cord stimulation as an intervention for motor recovery after motor complete spinal cord injury. J. Neurophysiol. 126, 1843–1859 (2021).

    Google Scholar 

  77. Azad, T. D. et al. Duraplasty in acute spinal cord injury: A systematic review. Eur. Spine J. https://doi.org/10.1007/s00586-025-08811-2 (2025).

    Google Scholar 

  78. Archavlis, E. et al. Pathophysiologic mechanisms of severe spinal cord injury and neuroplasticity following decompressive laminectomy and expansive duraplasty: A systematic review. Neurol. Int. 17, 57 (2025).

    Google Scholar 

  79. Streijger, F. et al. Duraplasty in traumatic thoracic spinal cord injury: Impact on spinal cord hemodynamics, tissue metabolism, histology, and behavioral recovery using a porcine model. J. Neurotrauma. 38, 2937–2955 (2021).

    Google Scholar 

  80. Cerro, P. D. et al. Neuropathological and motor impairments after incomplete cervical spinal cord injury in pigs. J. Neurotrauma. 38, 2956–2977 (2021).

    Google Scholar 

  81. Ziu, E., Weisbrod, L. J. & Mesfin, F. B. Spinal shock. in StatPearls [Internet] (StatPearls Publishing, 2024).

  82. Gayen, C. D. et al. Survival model of thoracic contusion spinal cord injury in the domestic pig. J. Neurotrauma. 40, 965–980 (2023).

    Google Scholar 

  83. Amiri, A. R., Fouyas, I. P., Cro, S. & Casey, A. T. Postoperative spinal epidural hematoma (SEH): Incidence, risk factors, onset, and management. Spine. J. 13, 134–140 (2013).

    Google Scholar 

  84. Moxon, K. A. et al. Long-term recordings of multiple, single-neurons for clinical applications: the emerging role of the bioactive microelectrode. Materials 2, 1762–1794 (2009).

    Google Scholar 

  85. McConnell, G. C. et al. Implanted neural electrodes cause chronic, local inflammation that is correlated with local neurodegeneration. J. Neural Eng. 6, 056003 (2009).

    Google Scholar 

  86. Szarowski, D. et al. Brain responses to micro-machined silicon devices. Brain Res. 983, 23–35 (2003).

    Google Scholar 

  87. Biran, R., Martin, D. C. & Tresco, P. A. The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull. J. Biomed. Mater. Res. A. 82, 169–178 (2007).

    Google Scholar 

  88. Nolta, N. F., Christensen, M. B., Crane, P. D., Skousen, J. L. & Tresco, P. A. BBB leakage, astrogliosis, and tissue loss correlate with silicon microelectrode array recording performance. Biomaterials 53, 753–762 (2015).

    Google Scholar 

  89. Subbaroyan, J., Martin, D. C. & Kipke, D. R. A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex. J. Neural Eng. 2, 103 (2005).

    Google Scholar 

  90. Wellman, S. M., Li, L., Yaxiaer, Y., McNamara, I. & Kozai, T. D. Revealing spatial and temporal patterns of cell death, glial proliferation, and blood-brain barrier dysfunction around implanted intracortical neural interfaces. Front. Neurosci. 13, 493 (2019).

    Google Scholar 

  91. Kozai, T. D., Jaquins-Gerstl, A. S., Vazquez, A. L., Michael, A. C. & Cui, X. T. Brain tissue responses to neural implants impact signal sensitivity and intervention strategies. ACS Chem. Neurosci. 6, 48–67 (2015).

    Google Scholar 

  92. Vedam-Mai, V. et al. The national DBS brain tissue network pilot study: need for more tissue and more standardization. Cell Tissue Banking 12, 219–231 (2011).

    Google Scholar 

  93. Orlowski, D. et al. Brain tissue reaction to deep brain stimulation—A longitudinal study of DBS in the Goettingen minipig. Neuromodulation 20, 417–423 (2017).

    Google Scholar 

  94. Grill, W. M. & Mortimer, J. T. Electrical properties of implant encapsulation tissue. Ann. Biomed. Eng. 22, 23–33 (1994).

    Google Scholar 

  95. Roitbak, T. & Syková, E. Diffusion barriers evoked in the rat cortex by reactive astrogliosis. Glia 28, 40–48 (1999).

    Google Scholar 

  96. Barrese, J. C. et al. Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates. J. Neural Eng. 10, 066014 (2013).

    Google Scholar 

  97. Suner, S., Fellows, M. R., Vargas-Irwin, C., Nakata, G. K. & Donoghue, J. P. Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex. IEEE Trans. Neural Syst. Rehabil. Eng. 13, 524–541 (2005).

    Google Scholar 

  98. Mushahwar, V. K. & Horch, K. W. Proposed specifications for a lumbar spinal cord electrode array for control of lower extremities in paraplegia. IEEE Trans. Rehabil. Eng. 5, 237–243 (1997).

    Google Scholar 

  99. Jankowska, E. & Roberts, W. An electrophysiological demonstration of the axonal projections of single spinal interneurones in the cat. J. Physiol. 222, 597–622 (1972).

    Google Scholar 

  100. Kim, Y.-T., Hitchcock, R. W., Bridge, M. J. & Tresco, P. A. Chronic response of adult rat brain tissue to implants anchored to the skull. Biomaterials 25, 2229–2237 (2004).

    Google Scholar 

  101. Vomero, M. et al. On the longevity of flexible neural interfaces: Establishing biostability of polyimide-based intracortical implants. Biomaterials 281, 121372 (2022).

    Google Scholar 

  102. Luan, L. et al. Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration. Sci. Adv. 3, e1601966 (2017).

    Google Scholar 

  103. Waters, C. M. Reactive oxygen species in mechanotransduction. Am. J. Physiol. Lung Cell. Mol. Physiol. 287, L484–L485 (2004).

    Google Scholar 

  104. Cheung, K. C. Implantable microscale neural interfaces. Biomed. Microdevices 9, 923–938 (2007).

    Google Scholar 

  105. Minev, I. R. et al. Electronic dura mater for long-term multimodal neural interfaces. Science 347, 159–163 (2015).

    Google Scholar 

  106. Kathe, C. et al. Wireless closed-loop optogenetics across the entire dorsoventral spinal cord in mice. Nat. Biotechnol. 40, 198–208 (2022).

    Google Scholar 

  107. Hanson, T. L., Diaz-Botia, C. A., Kharazia, V., Maharbiz, M. M. & Sabes, P. N. The “sewing machine” for minimally invasive neural recording. BioRxiv 578542 (2019).

  108. Bertelsen, A., Melo, J., Sánchez, E. & Borro, D. A review of surgical robots for spinal interventions. Int. J. Med. Robot. Comput. Assist. Surg. 9, 407–422 (2013).

    Google Scholar 

  109. Frederick, R. A., Meliane, I. Y., Joshi-Imre, A., Troyk, P. R. & Cogan, S. F. Activated Iridium oxide film (AIROF) electrodes for neural tissue stimulation. J. Neural Eng. 17, 056001 (2020).

    Google Scholar 

  110. Frederick, R. A., Troyk, P. R. & Cogan, S. F. Wireless transmission of voltage transients from a chronically implanted neural stimulation device. J. Neural Eng. 19, 026049 (2022).

    Google Scholar 

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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.

Author information

Authors and Affiliations

  1. Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada

    Soroush Mirkiani, Carly L. O’Sullivan, Amin Arefadib & Vivian K. Mushahwar

  2. Institute for Smart Augmentative and Restorative Technologies and Health Innovations (iSMART), University of Alberta, Edmonton, Canada

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

  3. Division of Physical Medicine and Rehabilitation, Department of Medicine, University of Alberta, Edmonton, AB, Canada

    Neil Tyreman, Katalin Sari, Don Wilson & Vivian K. Mushahwar

  4. Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, USA

    Omar Tawakol & Philip R. Troyk

  5. Division of Neurosurgery, Department of Surgery, University of Alberta, Edmonton, AB, Canada

    Richard Fox

Authors
  1. Soroush Mirkiani
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  2. Carly L. O’Sullivan
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  3. Amin Arefadib
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  4. Neil Tyreman
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  5. Katalin Sari
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  6. Don Wilson
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  7. Omar Tawakol
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  8. Philip R. Troyk
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  9. Richard Fox
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  10. Vivian K. Mushahwar
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Contributions

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.

Corresponding author

Correspondence to Vivian K. Mushahwar.

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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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  • Received: 26 October 2025

  • Accepted: 24 February 2026

  • Published: 24 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-42212-9

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