Stable softening bioelectronics: A paradigm for chronically viable ester-free neural interfaces such as spinal cord stimulation implants

Garcia-Sandoval, Aldo; Guerrero, Edgar; Hosseini, Seyed Mahmoud; Rocha-Flores, Pedro Emanuel; Rihani, Rashed; Black, Bryan; Pal, Ajay; Carmel, Jason B.; Pancrazio, Joseph J.; Voit, Walter

doi:10.1016/j.biomaterials.2021.121073

Cited by 6 publications

(3 citation statements)

References 50 publications

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“…In awake and freely moving rats, we tested spinal cord associative plasticity (SCAP) and its efficacy on physiology and function in rats with SCI. We used custom spinal stimulating electrodes that can be inserted into the thin epidural space over the cervical spinal cord, are supple enough to conform to the spinal cord, and move with the neck 16, 17 . First, we tested the motor cortex and spinal cord stimulation timing with the hypothesis that convergence in the spinal cord would produce the largest changes in physiology.…”

Section: Methodsmentioning

confidence: 99%

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Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury

Pal

Park

Ramamurthy

et al. 2020

Preprint

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Associative plasticity occurs when two stimuli converge on a common neural target. We sought to use the strong convergence between motor and sensory systems in the spinal cord to restore movement after spinal cord injury (SCI). We developed a paired motor cortex and dorsal spinal cord stimulation protocol to target this interaction called spinal cord associative plasticity (SCAP). Subthreshold spinal cord stimulation strongly augments motor cortex evoked potentials at the time they are paired, but only when they arrive synchronously in the spinal cord. We tested the hypothesis that this paired stimulation effect depended on cortical descending motor and spinal cord proprioceptive afferents. Selective inactivation of either of these pathways fully abrogated the paired stimulation effect. We then found that repetitive pairing in awake rats increased spinal excitability for hours after pairing ended. To apply this protocol as therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was just as strong in rats with cervical SCI as in un-injured rats, demonstrating that spared connections after SCI are sufficient to support this plasticity. When 30 minutes of paired stimulation was done over 10 days, the effect of pairing was sustained for weeks. In addition, H-reflex modulation improved, showing decreased hyperreflexia that also persisted for weeks. Importantly, repetitive paired stimulation supported enhanced recovery of forelimb dexterity in rats after SCI with no augmentation of injury-induced neuropathic pain. We conclude that SCAP strengthens sensory-motor connections within the spinal cord, resulting in decreased hyperreflexia and improved forelimb function after SCI.Significance StatementDespite evidence that electrical stimulation of spared nervous system connections can facilitate recovery after SCI, strongly overlapping sensory and motor connections in the spinal cord have not been targeted for therapy. Here we demonstrate a robust paired stimulation paradigm that depends on corticofugal and proprioceptive afferent convergence in the spinal cord. The paradigm, termed SCAP for spinal cord associative plasticity, produced large-scale physiological changes in a preclinical model of cervical SCI. Importantly, SCAP caused lasting improvements in dexterity and decreased hyperreflexia in rats with SCI. Thus, we have determined the neural circuits that drive SCAP and have preclinical evidence for its efficacy to restore function after incomplete cervical SCI, the most common SCI in people.

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Section: Methodsmentioning

confidence: 99%

“…One week after a cortical and EMG electrode implant, the rats went through another surgery to implant spinal stimulation electrodes, as described previously 2, 3 . Briefly, the head and the cervical spine were fixed in a stereotactic frame.…”

Section: Methodsmentioning

confidence: 99%

Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury

Pal

Park

Ramamurthy

et al. 2020

Preprint

Self Cite

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“…Regarding the challenge of inserting penetrating flexible neural probes, one family of materials which may hold promise is that of mechanically adaptive materials, which are designed to change their elastic modulus or shape in response to an environmental stimulus [71]. Using shape memory polymers [12,152,153] or other softening materials [154,155] it may be possible to insert implants in a rigid state without the use of rigid shuttles or other insertion aids, instead allowing the implant to change to a softer state over time to preserve favorable mechanical properties for long-term tissue integration.…”

Section: Emerging Substrate Materials and Architecturesmentioning

confidence: 99%

Lifetime engineering of bioelectronic implants with mechanically reliable thin film encapsulations

Niemiec,

Kim

2023

Prog. Biomed. Eng.

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While the importance of thin form factor and mechanical tissue biocompatibility has been made clear for next generation bioelectronic implants, material systems meeting these criteria still have not demonstrated sufficient long-term durability. This review provides an update on the materials used in modern bioelectronic implants as substrates and protective encapsulations, with a particular focus on flexible and conformable devices. We review how thin film encapsulations are known to fail due to mechanical stresses and environmental surroundings under processing and operating conditions. This information is then reflected in recommending state-of-the-art encapsulation strategies for designing mechanically reliable thin film bioelectronic interfaces. Finally, we assess the methods used to evaluate novel bioelectronic implant devices and the current state of their longevity based on encapsulation and substrate materials. We also provide insights for future testing to engineer long-lived bioelectronic implants more effectively and to make implantable bioelectronics a viable option for chronic diseases in accordance with each patient’s therapeutical timescale.

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Softening implantable bioelectronics: Material designs, applications, and future directions

Oh,

Lee,

Kim

et al. 2024

Biosensors and Bioelectronics

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Stable softening bioelectronics: A paradigm for chronically viable ester-free neural interfaces such as spinal cord stimulation implants

Cited by 6 publications

References 50 publications

Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury

Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury

Lifetime engineering of bioelectronic implants with mechanically reliable thin film encapsulations

Softening implantable bioelectronics: Material designs, applications, and future directions

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