Role of DAMPs in the modulation on neutrophils and macrophages response to a classic biomaterial (titanium)in vitro

Abstract

SUMMARY: Studies have shown that the nature (transient or chronic) and the magnitude of the inflammatory and immunological response, generated by an implantation, may be decisive in the clinical success or failure of the grafted material. Neutrophils and monocytes/macrophages are described to be recruited to the site of biomaterial implantation, but its role in generation and regulation of host response to biomaterial remains unknown. Also, it is not known how these cell types are activated upon its migration to grafting area, if by direct contact with the biomaterial (surface and/or components) or by molecules originated by tissue damage resulting from the implantation, such as DAMPs (damage-associated molecular patterns). Thus, the objective of this study is to evaluate the pattern of response developed by of neutrophils and monocytes/macrophages in response to a 'classic' biomaterial (titanium) in the presence/absence of DAMPs in vitro, using enzymatic and molecular analysis. In order to determine the pattern of macrophages response to titanium disks in the presence/absence of DAMPs, these cells will be characterized regarding the expression of markers of macrophages actived by classical (M1) and alternative (M2) pathway, such as the production of pro/anti-inflammatory cytokines and growth factors (TNF-±, IL-1², MMPs, TIMPs, TGF-², IL-10, IL-4, BMPs). Similarly, to determine the pattern of neutrophils response to titanium disks in the presence/absence of DAMPs, such cells will be analyzed regarding the production of NETs (neutrophil extracellular traps), as well the production of Myeloperoxidase (MPO), pro/anti-inflammatory cytokines and growth factors (TNF-±, IL-1², IL-8, TGF-², IL-10). A depth understanding of how the immune system interacts with these cells and how biomaterials or tissue-engineered constructs influence these interactions may prove pivotal to the safety, biocompatibility and function of the biomaterials.KEYWORDS: Biomaterial, titanium disk, inflammation, immune system, cytokines, macrophages, neutrophil extracellular traps (NETs) (AU)