Polymyxin B inhibits biphasic calcium phosphate degradation induced by lipopolysaccharide-activated human monocytes/macrophages

Abstract

Numerous cell types, such as monocytes and osteoclasts, are involved in calcified matrix degradation. In this context, calcium–phosphate ceramics present similar degradation processes in vivo and in vitro to those found in a natural calcified substrate. As the monocyte/macrophage lineage is among the first cells to appear in ceramic implantation sites, it is a key protagonist in inflammatory reaction and biodegradation mechanisms. This study investigated the ability of human monocytes/macrophages activated by various agents [lipopolysaccharides (LPS), polymyxin B (PMB)] to degrade biphasic calcium–phosphate ceramics. PMB sulfate is a bacteriostatic antibiotic that modulates LPS‐induced cell activities in vivo and in vitro. Degradation pits (about 10 μm) produced on the pellet surface by these monocytes were discrete, with well defined margins. LPS increased the degradation of calcium–phosphate ceramic (number of lacunae, mean pellet surface area degraded) in a dose‐dependent manner whereas polymyxin B downmodulated it significantly. The addition of 2 μg/mL of polymyxin B reduced the number of degradation lacunae and the extent of degraded surface area induced by 0.1 μg/mL LPS by 87% and 64%, respectively. Thus this cell culture system can be very useful in the study of cellular degradation of biomaterials and of the influence of therapeutic agents that may modulate these cell activities. © 1998 John Wiley & Sons, Inc. J. Biomed Mater Res, 40, 336–340, 1998