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On the use of Parylene C polymer as substrate for peripheral nerve electrodes.

ABSTRACT: Parylene C is a highly flexible polymer used in several biomedical implants. Since previous studies have reported valuable biocompatible and manufacturing characteristics for brain and intraneural implants, we tested its suitability as a substrate for peripheral nerve electrodes. We evaluated 1-year-aged in vitro samples, where no chemical differences were observed and only a slight deviation on Young's modulus was found. The foreign body reaction (FBR) to longitudinal Parylene C devices implanted in the rat sciatic nerve for 8 months was characterized. After 2 weeks, a capsule was formed around the device, which continued increasing up to 16 and 32 weeks. Histological analyses revealed two cell types implicated in the FBR: macrophages, in contact with the device, and fibroblasts, localized in the outermost zone after 8 weeks. Molecular analysis of implanted nerves comparing Parylene C and polyimide devices revealed a peak of inflammatory cytokines after 1?day of implant, returning to low levels thereafter. Only an increase of CCL2 and CCL3 was found at chronic time-points for both materials. Although no molecular differences in the FBR to both polymers were found, the thick tissue capsule formed around Parylene C puts some concern on its use as a scaffold for intraneural electrodes.

SUBMITTER: de la Oliva N

PROVIDER: S-EPMC5899141 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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On the use of Parylene C polymer as substrate for peripheral nerve electrodes.

de la Oliva Natàlia N Mueller Matthias M Stieglitz Thomas T Navarro Xavier X Del Valle Jaume J

Scientific reports 20180413 1

Parylene C is a highly flexible polymer used in several biomedical implants. Since previous studies have reported valuable biocompatible and manufacturing characteristics for brain and intraneural implants, we tested its suitability as a substrate for peripheral nerve electrodes. We evaluated 1-year-aged in vitro samples, where no chemical differences were observed and only a slight deviation on Young's modulus was found. The foreign body reaction (FBR) to longitudinal Parylene C devices implant ...[more]

PMID: 29654317

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Project description:Peripheral nerve injury accounts for roughly 2.8% of all trauma patients with an annual cost of 7 billion USD in the U.S. alone. Current treatment options rely on surgical intervention with the use of an autograft, despite associated shortcomings. Engineered nerve guidance conduits, stem cell therapies, and transient electrical stimulation have reported to increase speeds of functional recovery. As an alternative to the conduction effects of electrical stimulation, we have designed and optimized a nerve guidance conduit with aligned microchannels for the sustained release of a small molecule drug that promotes nerve impulse conduction. A biodegradable chitosan structure reinforced with drug-loaded halloysite nanotubes (HNT) was formed into a foam-like conduit with interconnected, longitudinally-aligned pores with an average pore size of 59.3?±?14.2??m. The aligned composite with HNTs produced anisotropic mechanical behavior with a Young's modulus of 0.33?±?0.1?MPa, very similar to that of native peripheral nerve. This manuscript reports on the sustained delivery of 4-Aminopyridine (4AP, molecular weight 94.1146?g/mol), a potassium-channel blocker as a growth factor alternative to enhance the rate of nerve regeneration. The conduit formulation released a total of 30?±?2% of the encapsulated 4AP in the first 7?days. Human Schwann cells showed elevated expression of key proteins such as nerve growth factor, myelin protein zero, and brain derived neurotrophic factor in a 4AP dose dependent manner. Preliminary in vivo studies in a critical-sized sciatic nerve defect in Wistar rats confirmed conduit suturability and strength to withstand ambulatory forces over 4?weeks of their implantation. Histological evaluations suggest conduit biocompatibility and Schwann cell infiltration and organization within the conduit and lumen. These nerve guidance conduits and 4AP sustained delivery may serve as an attractive strategy for nerve repair and regeneration.

Project description:Promoting axon growth after peripheral nerve injury may support recovery. Soluble laminin polymers formed at pH 4 (aLam) accelerate axon growth from adult dorsal root ganglion neurons in vitro. We used an adult rat model of a peripheral (peroneal) nerve crush to investigate whether an injection of aLam enhances axon growth and functional recovery in vivo. Rats that received an injection of aLam into the crush at 2 days post-injury show significant improvements in hind limb motor function at 2 and 5 weeks after injury compared with control rats that received phosphate-buffered saline. Functional improvement was not associated with changes in sensitivity to thermal or mechanical stimuli. Treatment with aLam decreased the occurrence of autophagia and abolished non-compliance with treadmill walking. Rats treated with aLam showed increased axon presence in the crush site at 2 weeks post-injury and larger axon diameter at 10 weeks post-injury compared with controls. Treatment with aLam did not affect Schwann cell presence or axon myelination. Our results demonstrated that aLam accelerates axon growth and maturity in a crushed peroneal nerve associated with expedited hind limb motor function recovery. Our data support the therapeutic potential of injectable aLam polymers for treatment of peripheral nerve crush injuries. STATEMENT OF SIGNIFICANCE: Incidence of peripheral nerve injury has been estimated to be as high as 5% of all cases entering a Level 1 trauma center and the majority of cases are young males. Peripheral nerves have some endogenous repair capabilities, but overall recovery of function remains limited, which typically has devastating effects on the individual, family, and society, as wages are lost and rehabilitation is extended until the nerves can repair. We report here that laminin polymers injected into a crush accelerated repair and recovery, had no adverse effects on sensory function, obliterated non-compliance for walking tests, and decreased the occurrence of autophagia. These data support the use of laminin polymers for safe and effective recovery after peripheral nerve injury.

Dataset Information

On the use of Parylene C polymer as substrate for peripheral nerve electrodes.

Publications

On the use of Parylene C polymer as substrate for peripheral nerve electrodes.

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