Human monocyte response to particulate biomaterials generated in vivo and in vitro

Abstract

We studied the ability of four clinically relevant particle species to stimulate human peripheral blood monocytes to release bone-resorbing agents, including interleukin-1 (both interleukin-1 alpha and interleukin-1 beta), interleukin-6, and prostaglandin E2. The species studied were titanium-6% aluminum-4% vanadium (TiAlV), commercially pure titanium, fabricated ultrahigh molecular weight polyethylene, and polyethylene retrieved from interfacial membranes of failed uncemented total hip arthroplasties. For all species, the mean size was less than 1 micron. Human peripheral blood monocytes were challenged with these particles in a uniform manner on the basis of surface area. Phorbol 12-myristate acetate, zymosan, and nonphagocytosable titanium particles served as controls. Stimulation of human monocytes is a function of the composition and concentration of particles. In this study, TiAlV particles appeared to be the most competent to elicit the synthesis and release of inflammatory mediators. Particles of commercially pure titanium and of fabricated ultrahigh molecular weight polyethylene also could induce the release of various cellular mediators, albeit at a lower level, whereas the particles of polyethylene retrieved from interfacial membranes were less stimulatory in these short-term in vitro experiments.

The role of adsorbed endotoxin in particle‐induced stimulation of cytokine release

“…An additional factor relates to the marked variability in the particulate test materials and specific culture conditions. Numerous investigators have shown that particle size, shape, surface roughness, relative hydrophobicity or hydrophilicity and composition, are critical factors in defining the consequences of particle-cell interactions [38,35,40,49,52,56]. When these properties are compared in different studies, it is clear that there is marked heterogeneity in the materials that are being evaluated.…”

“…The particles were washed three times in excess PBS and resuspended in PBS. Heat i/zurrirution: Following three washes in 70% ethanol as stated previously, the particles were autoclaved for I h and subsequently heated in a baking oven at 175 "C for 3 h [47]. following which the particles were resuspended in PBS.…”

“…Wear debris released from the implants contributes to loosening by activating macrophages, inducing peri-implant granulomatous inflammation, and subsequently leading to osteolysis [20,32,37,48,55,59]. Numerous in vitro models have demonstrated the capacity of wear particles to stimulate the release of soluble pro-inflanimatory products with the capacity to induce local bone resorption [4,18,22,27,47,49,50]. The biological activity of wear particles has been attributed to several factors, such as the physical and chemical properties of the material, including size, morphology, and composition, as well as the effects of surface adsorbed serum-derived proteins [4,24,26,36,47,49].…”

“…Numerous in vitro models have demonstrated the capacity of wear particles to stimulate the release of soluble pro-inflanimatory products with the capacity to induce local bone resorption [4,18,22,27,47,49,50]. The biological activity of wear particles has been attributed to several factors, such as the physical and chemical properties of the material, including size, morphology, and composition, as well as the effects of surface adsorbed serum-derived proteins [4,24,26,36,47,49]. Recent observations have demonstrated that lipopolysaccharide ( LPS) can significantly modulate the cell response to wear debris in the in vitro models [6,8,25,44].…”

The John Charnley Award: An Accurate and Sensitive Method to Separate, Display, and Characterize Wear Debris: Part 1: Polyethylene Particles

“…To date, methods developed to assess the biologic reactivity to wear debris have considered the sizes, compositions, and surface areas of the particles [22,30,33,44,45]. However, a careful reevaluation of the biologic activity for crosslinked PE should take into account the overall volume in addition to the particle size, composition, and area and should be based on a highly precise method for obtaining purified and well-characterized PE particles.…”