Role of the Complement System in the Response to Orthopedic Biomaterials

Abstract

Various synthetic biomaterials are used to replace lost or damaged bone tissue that, more or less successfully, osseointegrate into the bone environment. Almost all biomaterials used in orthopedic medicine activate the host-immune system to a certain degree. The complement system, which is a crucial arm of innate immunity, is rapidly activated by an implanted foreign material into the human body, and it is intensely studied regarding blood-contacting medical devices. In contrast, much less is known regarding the role of the complement system in response to implanted bone biomaterials. However, given the increasing knowledge of the complement regulation of bone homeostasis, regeneration, and inflammation, complement involvement in the immune response following biomaterial implantation into bone appears very likely. Moreover, bone cells can produce complement factors and are target cells of activated complement. Therefore, new bone formation or bone resorption around the implant area might be greatly influenced by the complement system. This review aims to summarize the current knowledge on biomaterial-mediated complement activation, with a focus on materials primarily used in orthopedic medicine. In addition, methods to modify the interactions between the complement system and bone biomaterials are discussed, which might favor osseointegration and improve the functionality of the device.

PEGylation of Deferoxamine for Improving the Stability, Cytotoxicity, and Iron-Overload in an Experimental Stroke Model in Rats

“…As a primary component of the innate immune system, complement activation is regarded as an essential factor of hemocompatibility (Ekdahl et al, 2011). When the biocompatibility of biomaterials is poor, the main pathway activated is the alternative pathway, which is associated with the creation of the anaphylatoxins C3a and C5a (Mödinger et al, 2018). In our study, the concentrations of C3a and C5a in plasma exposed to PEGylated DFO were measured as indicators of complement activation.…”

Biomimetic sponges improve muscle structure and function following volumetric muscle loss

“…In this study, the gene expression complement opsonin C3 was significantly higher in the sponge treated muscles compared to uninjured controls. It has been shown that implantation of biomaterials can activate the complement system [38]. Besides initiating inflammation, the complement system also plays a role in muscle repair.…”

Hemocompatibility of Carbon Nanostructures

“…The anaphylatoxin C3a induces pro-inflammatory effects, including neutrophil and macrophage chemoattraction, while surface-immobilized C3b recruits and activates leukocytes and binds to pathogens inducing their phagocytosis. C3b also takes part in the formation of the C3 and C5 convertase, which generates the pro-inflammatory anaphylatoxin C5a [51] and the fragment C5b, which may induce the formation of the terminal complement complexes (TCC or sC5b-9). Surface adsorbed plasma proteins play a key role in the activation of the complement system, as specific conformational changes in the molecular structure of adsorbed proteins can expose varying number of acceptor sites to C3 fragments [52].…”