The role of Toll-like receptor signaling in the macrophage response to implanted materials
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Prospective Article
The role of Toll-like receptor signaling in the macrophage response to implanted materials Laura A. McKiel , Kimberly A. Woodhouse , and Lindsay E. Fitzpatrick Dupuis Hall, Room 201, 19 Division St, Kingston, Ontario, Canada K7K 3N6
, Department of Chemical Engineering, Queen’s University,
Address all correspondence to Lindsay E. Fitzpatrick at lindsay.fi[email protected] (Received 19 August 2019; accepted 20 November 2019)
Abstract Inflammation is facilitated largely by macrophages and other white blood cells, which recognize and respond to evolutionarily conserved damage-associated molecular patterns that are released upon tissue injury and cell stress. Damage-associated molecular patterns are known to bind Toll-like receptors (TLRs) and initiate inflammatory responses through MyD88-dependent NF-κB signaling. Biomaterial implantation activates the innate immune system, resulting in a chronic inflammatory response known as a foreign body reaction (FBR). In this review, the authors discuss the current understanding of damage-initiated TLR signaling in the FBR and the significance of this response in the success of implanted devices.
Introduction The host response to implants is a complex immune-mediated foreign body reaction (FBR) that continues to represent a significant challenge to the field of biomaterials and biomedical engineering.[1] While the severity and extent to which an implant elicits a FBR varies, depending on biological factors (e.g., implant location, degree of trauma to implant site)[2–4] and material factors (e.g., implant shape and size, material chemistry, topography, porosity, stiffness),[5–8] a classical FBR can be described as overlapping and fluid phases of an aberrant wound healing response: protein adsorption, inflammation, and fibrous encapsulation of the implant.[1] Upon implantation in soft tissue (e.g., sensors, drug delivery devices, tissue replacements), the material surface is immediately fouled by the adsorption of proteins (and other molecules) from the injured tissue and blood vessels at the implant site, and a provisional fibrin matrix is formed around the implant.[9] This acute inflammatory response, which can last up to 7 days, is further stimulated by the tissue damage, and innate immune cells are recruited to the implant site.[10,11] At the tissue-material interface, immune cells (also known as white blood cells or leukocytes) recognize and adhere to the implant surface via the adsorbed protein layer.[12] While multiple circulating and tissue-resident leukocytes are involved in biomaterial host responses, a type of leukocyte known as macrophages are widely recognized as key mediators of the FBR and direct the immune recognition and response to the foreign materials.[1,13,14] Macrophages are also phagocytic, meaning that they can engulf and ingest small particles (i.e., microparticles), cellular debris, and bacteria.[15] Macrophage adhesion and activation on material surfaces implanted in soft tissue is well
documented.[5,6,8,16–18] Adherent macrophages may fu
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