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Screening biomaterials for stimulation of nitric oxide‐mediated inflammation
Author(s) -
Lyle Daniel B.,
Shallcross Jonathan C.,
Durfor Charles N.,
Hitchins Victoria M.,
Breger Joyce C.,
Langone John J.
Publication year - 2009
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32060
Subject(s) - nitric oxide , lipopolysaccharide , stimulation , inflammation , materials science , macrophage , hyaluronic acid , in vitro , immune system , pharmacology , biomedical engineering , medicine , immunology , biochemistry , chemistry , anatomy
Inflammatory reactions to biomaterials may include macrophage‐mediated generation of nitric oxide (NO), which may harm patient tissue or potentially interfere with proper function of an implanted device. RAW 264.7 cells were grown in culture and treated at various times with lipopolysaccharide (LPS, endotoxin), murine recombinant γ‐interferon (mrIFN‐γ), and different preparations of hyaluronic acid (HA). Increase in fluorescence of 2,3‐diaminonaphthalene (DAN) allowed for detection of initial (24 h or less) NO inflammatory responses of RAW 264.7 to LPS from E. coli O26:B6. By looking at early time points, mrIFN‐γ augmentation of the LPS effect was observed, simulating a complex immune reaction. Activation through nuclear factor ‐ κB (NF‐κB), was confirmed in this system by parthenolide inhibition of LPS stimulation. Stimulation of RAW 264.7 by different HA preparations resulted in NO responses that correlated with the amount of LPS present. In the presence of mrIFN‐γ, a significant inflammatory reaction to HA was observed when the concentration of contaminating LPS was as low as 0.15 EU/mL. NO production in the presence of mrIFN‐γ by RAW 264.7 may serve as a convenient in vitro system to routinely screen biomaterials for potentially harmful macrophage‐mediated inflammation whereby the safety of implanted medical devices might be compromised. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009