Complement proteins regulating macrophage polarisation on biomaterials

Abstract

One of the events occurring when a biomaterial is implanted in an host is the protein deposition onto its surface, which might regulate cell responses. When a biomaterial displays a compromised biocompatibility, distinct complement pathways can be activated to produce a foreign body reaction. In this article, we have designed different types of biomaterial surfaces to study the inflammation process. Here, we used different concentrations of (3-glycidoxypropyl)-trimethoxysilane (GPTMS), an organicallymodified alkoxysilane as a precursor for the synthesis of various types of sol-gel materials functionalizing coatings for titanium implants to regulate biological responses. Our results showed that increasing GPTMS concentration slightly enhanced the osteogenic potential of MC3T3-E1 cells in vitro, which seems linked to upregulation of TGF-β expression. Moreover, greater GPTMS surface concentrations induced greater secretion of TNF-α and IL-10 on RAW 264.7 macrophages. When implanted into rabbit tibia, osseointegration decreased with higher GPTMS concentrations. Interestingly, higher deposition of complement-related proteins C-reactive protein (CRP) and ficolin-2 (FCN2), two main activators of distinct complement pathways, was observed. Taking all together, inflammatory potential increase seems to be GPTMS concentrationdependent. Our results show that a greater adsorption of complement proteins can condition macrophage polarization.

Evaluation of the inflammatory responses to sol–gel coatings with distinct biocompatibility levels

“…In RAW264.7 cells exposed to LPS, IL‐10 secretion is increased 35 . As described in Araújo‐Gomes et al, 27 GPTMS presents an epoxy ring in its structure that might mimic LPS. However, IL‐10 secretion was not significantly higher on 50V50G.…”

“…This fact can be associated with the 35% of GPTMS incorporated in the coating network. GPTMS‐derived sol–gel materials showed an increased inflammatory potential, which in turn was directly correlated with a higher affinity of complement proteins to the material surface 27 . However, when comparing to 50M50G and 50V50G, we can conclude that this may be due to the lower percentage of the compound, therefore not compromising biocompatibility.…”

“…The composition, conformation and amount of the bound proteins is regulated their specific affinity and the biomaterial characteristics. Distinct biological responses can result by changing the surface and consequent protein adsorption; more specifically, emerging data suggest that the modulation of immune cells is directly driven by complement protein adsorption, affecting the in vivo biocompatibility of a material 27 . Immune cells interact closely with complement proteins inducing an initial inflammatory response that propagates depending on multiple factors and at implantation site activate and promote additional cellular events.…”

Protein adsorption/desorption dynamics on Ca-enriched titanium surfaces: biological implications

“…The adsorption of proteins on the material surface significantly affects its biological outcome [29,30]. As a result, understanding the protein layer formation onto biomaterials is of paramount importance to control their complex interaction with the biological environment [20].…”

Recent Advances in Antiinflammatory Material Design

“…Such silanefunctionalized titanium enabled to increase the ratio of M2 macrophages. [91] Moreover, silane can own amino groups that can be reactive for the addition of other molecules. [92] Thus, glycosaminoglycans could be grafted to amino-terminated surfaces to improve the anti-inflammatory properties, as it has been described previously.…”