Biological response to implanted intraneural electrodes

The foreign body reaction (FBR) is an immune-mediated response to any device implanted in the body. Several studies have shown that it is characterized by a first inflammatory phase followed by a tissue remodeling phase, which results in the encapsulation of the foreign body. This encapsulation is thought to cause, among other factors, the progressive decline in function reported in neural electrodes, which should remain chronically implanted in the body to generate and record nerve signals from the nervous tissue. In this thesis, a detailed characterization of the FBR to intraneural electrodes has been performed, in order to determine feasible therapeutic strategies to reduce the FBR and to improve the long-term function of chronic implanted intraneural electrodes. Our results show that the immune infiltration in the nerve peaked after two weeks of implant, without differences between two polymers intended to be used as electrode substrate (i.e., polyimide and Parylene C). However, the tissue deposition around both polymers evolved differently at chronic time points. While the capsule around polyimide devices peaked after two weeks and was stabilized after that up to 8 months, the capsule around Parylene C devices had a first peak at week 2 and it continued increasing after a resting period of 4-8 weeks to reach a second maximum at week 16. Molecular analysis of implanted nerves showed no differences between the FBR to both polymers in the inflammatory and tissue remodeling studied factors. The two main phases described in the FBR in peripheral nerves have determined possible therapeutic strategies to reduce this reaction. Among the several drugs tested, only dexamethasone significantly reduced the infiltration of macrophages and the thickness of the capsule around both polymers. Moreover, dexamethasone treatment improved the long-term function of transversal intraneural electrodes, particularly in terms of stimulation properties. In conclusion, the FBR to intraneural devices shows a similar pattern than the reported in other host tissues such as the subcutaneous and the peritoneal spaces. Moreover, differences in the FBR between polyimide and Parylene C have been observed, which would rule Parylene C out as a substrate for chronically implanted intraneural electrodes. The FBR characterization has allowed testing several therapeutic strategies to reduce this response, such as dexamethasone. In fact, dexamethasone treatment has improved the outcome of chronic implanted intraneural electrodes, may be due to a reduction in the cellular infiltration and tissue deposition.