Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics

Abstract

The implantation of any foreign material into the body leads to the development of an inflammatory and fibrotic process—the foreign body reaction (FBR). Upon implantation into a tissue, cells of the immune system become attracted to the foreign material and attempt to degrade it. If this degradation fails, fibroblasts envelop the material and form a physical barrier to isolate it from the rest of the body. Long-term implantation of medical devices faces a great challenge presented by FBR, as the cellular response disrupts the interface between implant and its target tissue. This is particularly true for nerve neuroprosthetic implants—devices implanted into nerves to address conditions such as sensory loss, muscle paralysis, chronic pain, and epilepsy. Nerve neuroprosthetics rely on tight interfacing between nerve tissue and electrodes to detect the tiny electrical signals carried by axons, and/or electrically stimulate small subsets of axons within a nerve. Moreover, as advances in microfabrication drive the field to increasingly miniaturized nerve implants, the need for a stable, intimate implant-tissue interface is likely to quickly become a limiting factor for the development of new neuroprosthetic implant technologies. Here, we provide an overview of the material-cell interactions leading to the development of FBR. We review current nerve neuroprosthetic technologies (cuff, penetrating, and regenerative interfaces) and how long-term function of these is limited by FBR. Finally, we discuss how material properties (such as stiffness and size), pharmacological therapies, or use of biodegradable materials may be exploited to minimize FBR to nerve neuroprosthetic implants and improve their long-term stability.

Mobilizing Endogenous Repair Through Understanding Immune Reaction With Biomaterials

“…They are known to attach to the biomaterial surface and release a host of inflammatory cytokines and Reactive Oxygen Species (ROS) ( Hernandez-Pando et al, 2000 ; Anderson et al, 2008 ). The cytokines expressed and the formation of FBGCs are largely determined by the biomaterial’s properties such as hydrophobicity or rigidity ( Carnicer-Lombarte et al, 2021 ).…”

3D Printed Multiphasic Scaffolds for Osteochondral Repair: Challenges and Opportunities

“…In time, the new mature tissue may take over the mechanical function of the implanted scaffold in degradable scaffolds. However, the immediate stiffness mismatch or inadequate tuning of the degradation profile of the scaffold to that of the production of mature tissue, can cause the implant to fail due to the increased foreign body reaction and inflammatory response or large differences in the way the implant and tissue respond to applied forces [185][186][187][188]. This is in contrast to strategies, such as internal fixation devices, which are non-degradable and designed to retain their function immediately and over the life of the device/treatment (that may include prolonged load bearing and full range of motion of the joint) [189].…”

Neurosensory Prosthetics: An Integral Neuromodulation Part of Bioelectronic Device

“…Acute inflammation is followed by chronic inflammation, which later subsides, resulting in a dense collagenous encapsulation of the implant, isolating it from the host body, and causing a subsequent loss of function. Neuro-prosthetics, are particularly vulnerable to FBR, since the fibrotic encapsulation damages and displaces the target neuronal tissue, and forms a high-impedance layer that weakens the interception of electrode signals and dissipates stimulating electrode currents ( Carnicer-Lombarte et al, 2021 ).…”

“…Approaches to modify an electrode-neural interface to reduce FBR are beyond the scope of this review and are well illustrated in other reviews ( Lotti et al, 2017 ; Carnicer-Lombarte et al, 2021 ).…”