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Defining critical inflammatory parameters for endotoxin impurity in manufactured alginate microcapsules
Author(s) -
Breger Joyce C.,
Lyle Daniel B.,
Shallcross Jonathan C.,
Langone John J.,
Wang Nam Sun
Publication year - 2009
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.31452
Subject(s) - lipopolysaccharide , nitric oxide , chemistry , nitrite , inflammatory response , interferon gamma , macrophage , inflammation , immunology , biochemistry , in vitro , medicine , nitrate , organic chemistry
Since current purification methods cannot completely remove all traces of endotoxin in biomaterials intended for use in implantable or blood‐contacting devices, acceptable levels of endotoxin contamination that will not cause a significant inflammatory reaction need to be defined. Inflammatory reactions to biomaterials may include production of high concentrations of potentially harmful nitric oxide (NO) generated by macrophages. Nitrite accumulation was measured from RAW264.7 cells treated with either lipopolysaccharide (LPS) free in solution or defined quantities of LPS incorporated into alginate in the absence or presence of murine interferon‐γ (mrIFN‐γ). In the absence of IFN‐γ, significant NO production by RAW 264.7 cells occurred for LPS levels down to 0.018 EU/mL. In the presence of mrIFN‐γ, the lowest concentration of LPS tested in solution (0.006 EU/mL) elicited a significant increase in NO production. In the absence or presence of mrIFN‐γ, five times the concentration of LPS incorporated into alginate as compared to LPS free in solution was necessary to elicit a similar NO response by RAW264.7. These results demonstrate that very low concentrations of endotoxin can elicit significant NO responses from macrophages, particularly when inflammatory cytokines are present. Biomaterials may sequester endotoxin, resulting in lower inflammatory reactions that otherwise might be expected. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009