Invasive Intraneural Interfaces: Foreign Body Reaction Issues

Abstract

Intraneural interfaces are stimulation/registration devices designed to couple the peripheral nervous system (PNS) with the environment. Over the last years, their use has increased in a wide range of applications, such as the control of a new generation of neural-interfaced prostheses. At present, the success of this technology is limited by an electrical impedance increase, due to an inflammatory response called foreign body reaction (FBR), which leads to the formation of a fibrotic tissue around the interface, eventually causing an inefficient transduction of the electrical signal. Based on recent developments in biomaterials and inflammatory/fibrotic pathologies, we explore and select the biological solutions that might be adopted in the neural interfaces FBR context: modifications of the interface surface, such as organic and synthetic coatings; the use of specific drugs or molecular biology tools to target the microenvironment around the interface; the development of bio-engineered-scaffold to reduce immune response and promote interface-tissue integration. By linking what we believe are the major crucial steps of the FBR process with related solutions, we point out the main issues that future research has to focus on: biocompatibility without losing signal conduction properties, good reproducible in vitro/in vivo models, drugs exhaustion and undesired side effects. The underlined pros and cons of proposed solutions show clearly the importance of a better understanding of all the molecular and cellular pathways involved and the need of a multi-target action based on a bio-engineered combination approach.

Immune-informed mucin hydrogels evade fibrotic foreign body response in vivo

“…We focused our 9 attention on macrophages (CD68 + CD11b + ) and other myeloid cells (CD68 -Gr1 low/-CD11b + ) that were predominant fractions of immune cells sorted by FACS (Figure 4, S-4). Macrophages are especially relevant in this context since they display remarkable functional plasticity and participate in the host defence, immune regulation, and tissue repair, all aspects playing a pivotal role in mediating implant-triggered fibrosis 3,34,35 .…”

“…An universal challenge for functional implants such as encapsulated cells 1 , sensors 2 , electrodes 3 , and drug-eluting materials 4 is their rapid isolation from the body by a fibrotic capsule mediated by a foreign body reaction (FBR). The FBR starts immediately after implantation with the passive absorption of proteins onto the implant.…”

“…Materials conjugated with CD47 could prevent macrophage attachment, activation, and phagocytosis 17,18 , while polystyrene grafted with CD200 decreased the expression of TNF-α and IL 6 in macrophages 19 . 3 Mucin glycoproteins have emerged as another important part of the immune regulatory arsenal in mammals. Mucins are either secreted to form the mucus gel that covers the mucosal epithelia, or expressed as cell transmembrane proteins as a main component of the cell glycocalyx.…”

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

“…It is characterized by an initial inflammatory phase, followed by an inflammatory resolution and tissue remodeling phase that results in the formation of a fibrous tissue capsule around the device (Luttikhuizen et al, ; Anderson et al, ). In the case of an intraneural electrode, this encapsulation results in a progressive decline in signal level and increase in stimulation threshold, because the scar tissue gradually separates axons away from the contacts (Lago et al, ; Rossini et al, ; Christensen et al, ; Raspopovic et al, ; Wurth et al, ; Lotti et al, ).…”

Bionic Intrafascicular Interfaces for Recording and Stimulating Peripheral Nerve Fibers

“…Various materials have been used to fabricate or coat micro electrodes in order to increase their effective surface area in order to enhance their capacity for safe charge delivery [72,73]. …”