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A Biodegradable Piezoelectric Vertebral Implant for Programmable Electro-neuromodulation in Spinal Cord Injury

ABSTRACT: Spinal cord stimulation is a promising strategy for functional recovery after spinal cord injury (SCI), but conventional electronic implants pose surgical and long-term risks. Here, we report a biodegradable piezoelectric cryogel (Piezo Gel) that enables programmable electro-neuromodulation without implanted electronics. Mimicking spinal biomechanics, Piezo Gel converts physiological movement into localized endogenous electric fields, while externally applied ultrasound (US) amplifies its electrical output, enabling on-demand in situ programming. In a rat model of acute severe SCI, US-activated Piezo Gel significantly enhanced locomotor recovery, improved Basso–Beattie–Bresnahan (BBB) scores, and promoted bladder functional remodeling. In a mild contusion model, we further implemented a phase-adaptive neuromodulation strategy, shifting from US-driven stimulation during acute immobility to movement-driven stimulation during subacute rehabilitation, aligning with the evolving spinal microenvironment. This sequential programming resulted in substantial restoration of coordinated gait. Together, this work establishes an electronic-free, programmable electro-neuromodulation paradigm that integrates US and physiological motion, offering a clinically translatable approach for SCI repair.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE326580 | GEO | 2026/06/21

REPOSITORIES: GEO

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Project description:Spinal cord injury (SCI) causes severe bone loss and disrupts connections between higher centers in the central nervous system (CNS) and bone. Muscle contraction elicited by functional electrical stimulation (FES) partially protects against loss of bone but cellular and molecular events by which this occurs are unknown. Here, using a rat model, we characterized effects of 7 days of contraction-induced loading of tibia and fibula due to FES when begun 16 weeks after SCI. SCI reduced tibial and femoral BMD by 12-17% and promoted bone resorption, as indicated by increased serum CTX; SCI-related changes in CTX were reversed by FES. In cultures of bone marrow cell-derived cells, SCI increased the number of osteoclasts and mRNA levels of the several osteoclast differentiation markers; these changes were significantly reversed by FES. The number of osteoblasts was also reduced by SCI as was the ratio of OPG/RANKL mRNAs therein; the unfavorable change in OPG/RANKL ratio was partially reversed by FES. cDNA microarray analysis revealed that alterations in genes involved in signaling through Wnt, FSH/LH, PTH and calcineurin/NFAT pathways may be linked to the favorable action of FES on SCI-induced bone resorption. In particular, SCI increased levels of the Wnt inhibitors DKK1, sFRP2 and SOST in osteoblasts, These effects were completely or partially reversed by FES. Our results demonstrate an anti-bone resorptive activity of acute FES in bone loss after SCI and suggest potential underlying mechanisms, among them involving increased Wnt signaling to cause more favorable ratios of OPG and RANKL for the inhibition of osteoclastogenesis. The present study indicates that the effects of bone reloading on SCI- related bone remodeling occurred independently of the effects of higher CNS centers on bone. Implantation of the FES microstimulators was performed 14 weeks after SCI. The FES was begun during the 16th week following spinal cord transection. Stimulation was provided for 60 minutes on each training day and consisted of brief periods of contraction (2 seconds) at 40 Hz at 1.5 V with longer periods of rest (18 seconds). Animals received FES on 7 consecutive days; collection of blood and tissues occurred at day at after initiating FES, as described below. The SCI-Sham FES animals received the implant surgery and gastrocnemius ablation during the 14th week after the spinal cord transection, but did not have a stimulator unit inserted; samples were collected from these animals at week 17. To provide age-matched non-SCI controls, additional animals underwent a sham-SCI surgery identical to that for the SCI animals, except that the spinal cord was not transected. Tissues were collected from these animals at 12-14 weeks after surgery. Of note, at this age, animals were sexually mature and their growth minimal. To collect blood and tissues, animals were anesthetized by inhalation of isofluorane followed by removal of the soleus and plantaris muscles after careful dissection and collection of blood by ventricular puncture and aspiration. Animals were euthanized by aortic transaction and tibia and femur were removed as a single piece, leaving the knee joint intact, and placed in a-MEM for isolation of bone marrow cells. Muscles were weighed; weights are expressed after being normalized to body weight before SCI or sham-SCI surgeries to control for individual variations in size.

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A Biodegradable Piezoelectric Vertebral Implant for Programmable Electro-neuromodulation in Spinal Cord Injury

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