Time course study of long‐term biocompatibility and foreign body reaction to intraneural polyimide‐based implants

Oliva, Natàlia de la; Navarro, Xavier; Valle, Jaume del

doi:10.1002/jbm.a.36274

Cited by 48 publications

(44 citation statements)

References 62 publications

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“…Specifically, the encapsulation thickness surrounding the SW implanted nerves was ≈12 µm compared to its PW counterpart, ≈30 µm. Encapsulation (30 µm) is similar to the values reported in Olivia et al evaluating the chronic foreign body response of tf‐LIFE electrodes at 4 weeks (≈23 µm) . PW showed significant reduction in axon size, compared to sham and SW implants across all bins (Figure d).…”

Section: Introductionsupporting

confidence: 80%

Soft Conducting Elastomer for Peripheral Nerve Interface

Zheng

Woeppel

Griffith

et al. 2019

Adv Healthcare Materials

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State‐of‐the‐art intraneural electrodes made from silicon or polyimide substrates have shown promise in selectively modulating efferent and afferent activity in the peripheral nervous system. However, when chronically implanted, these devices trigger a multiphase foreign body response ending in device encapsulation. The presence of encapsulation increases the distance between the electrode and the excitable tissue, which not only reduces the recordable signal amplitude but also requires increased current to activate nearby axons. Herein, this study reports a novel conducting polymer based intraneural electrode which has Young's moduli similar to that of nerve tissue. The study first describes material optimization of the soft wire conductive matrix and evaluates their mechanical and electrochemical properties. Second, the study demonstrates 3T3 cell survival when cultured with media eluted from the soft wires. Third, the study presents acute in vivo functionality for stimulation of peripheral nerves to evoke force and compound muscle action potential in a rat model. Furthermore, comprehensive histological analyses show that soft wires elicit significantly less scar tissue encapsulation, less changes to axon size, density and morphology, and reduced macrophage activation compared to polyimide implants in the sciatic nerves at 1 month postimplantation.

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Section: Introductionsupporting

confidence: 80%

Soft Conducting Elastomer for Peripheral Nerve Interface

Zheng

Woeppel

Griffith

et al. 2019

Adv Healthcare Materials

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“…We have recently characterized the extent of the inflammatory and the remodeling phases of the FBR to longitudinal implants in the peripheral nerve (De la Oliva, Navarro, and del Valle, ), thus determining possible targets for reducing the encapsulation and improving electrode functional outcome. The aim of this study is to evaluate the effect of different treatments to modulate the FBR and to reduce capsule thickness around longitudinal parylene C intraneural implants inserted in the rat sciatic nerve.…”

mentioning

confidence: 99%

Dexamethasone Reduces the Foreign Body Reaction to Intraneural Electrode Implants in the Peripheral Nerve of the Rat

Oliva

Navarro

Valle

2018

The Anatomical Record

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Intraneural electrodes must be in intimate contact with nerve fibers to have a proper function, but this interface is compromised due to the foreign body reaction (FBR). The FBR is characterized by a first inflammatory phase followed by a second anti-inflammatory and fibrotic phase, which results in the formation of a tissue capsule around the implant, causing physical separation between the active sites of the electrode and the nerve fibers. We have tested systemically several anti-inflammatory drugs such as dexamethasone (subcutaneous), ibuprofen and maraviroc (oral) to reduce macrophage activation, as well as clodronate liposomes (intraperitoneal) to reduce monocyte/macrophage infiltration, and sildenafil (oral) as an antifibrotic drug to reduce collagen deposition in an FBR model with longitudinal Parylene C intraneural implants in the rat sciatic nerve. Treatment with dexamethasone, ibuprofen, or clodronate significantly reduced the inflammatory reaction in the nerve in comparison to the saline group after 2 weeks of the implant, whereas sildenafil and maraviroc had no effect on infiltration of macrophages in the nerve. However, only dexamethasone was able to significantly reduce the matrix deposition around the implant. Similar positive results were obtained with dexamethasone in the case of polyimide-based intraneural implants, another polymer substrate for the electrode. These results indicate that inflammation triggers the FBR in peripheral nerves, and that anti-inflammatory treatment with dexamethasone may have beneficial effects on lengthening intraneural interface functionality.Advanced neuroprostheses are intended to link the human nervous system with electronic or robotic prostheses, with the aim of restoring motor and sensory functions lost after neural injuries or amputations. Various neuroprosthetic systems include an interface with the peripheral nerve.

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“…The biocompatibility of various surfaces including SU‐8, Parylene‐C, polyimide, and polydimethylsiloxane (PDMS) has been recently investigated with positive outcomes, especially where the surfaces were nanostructured in later manufacturing processes . Extended in vivo studies showed that Parylene‐C had good chemical stability and low glial scarring for small implants, but had enhanced tissue encapsulation compared to polyimide in chronically implanted peripheral interfaces …”

Section: Biocompatibilitymentioning

confidence: 99%