Effect of size and dose on bone resorption activity of macrophages byin vitro clinically relevant ultra high molecular weight polyethylene particles

Abstract

Polyethylene wear debris generated at the bearing surfaces of total artificial hip joints is thought to play an important role in the periprosthetic osteolysis and ultimately the aseptic loosening of these prostheses. The macrophage is believed to be central to this process by releasing various cytokines and other mediators of osteolysis upon phagocytosis of the polyethylene wear debris. This study evaluated the in vitro bone resorption response of C3H murine peritoneal macrophages to clinically relevant GUR 1120 polyethylene particles. Macrophages were co-cultured in vitro with GUR 1120 particles with a mean size of 0.24, 0.45, 1.71, and 7.62, and GUR 1120 polyethylene resin with a mean size of 88 microm at various particle volume (microm)(3): macrophage ratios (0.1:1; 1:1; 10:1; and 100:1). The conditioned supernatants were incubated with (45)calcium radio-labeled mouse calvariae, and bone resorption was measured as (45)calcium release. The results showed that the 0.24 microm particles stimulated the macrophages to generate bone resorbing activity at a ratio of 10(microm)(3) per macrophage. The 0.45 and 1.71 microm particles were active at a ratio of 100( microm)(3) per macrophage, and the 7.62 and 88 microm particles were inactive at all the doses tested. The co-culture supernatants were also assayed for TNF-alpha, IL-1beta, IL-6, and PGE(2). The results followed the same trend for particle size and volume dose to that observed for the bone resorbing activity. This study has demonstrated, for the first time, the importance of size and dose of clinically relevant polyethylene particles on the osteolytic response of macrophages in vitro.

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

“…In vitro models have shown the osteolytic potential of PE wear debris is affected by volume of particles, as well as their size distribution [17,21,22,36]. With followup exceeding 12 years, the incidence and extent of osteolysis have been markedly lower for hip arthroplasties using crosslinked PEs [5,27,28].…”

Aseptic loosening, not only a question of wear: A review of different theories

“…The resulting bone loss will enlarge the interface and ease the flow of joint fluid, resulting in higher transportation capacity of the debris and gradual loosening of the implant. Harris et al 1976Willert 1977 PE-particle Howie et al 1988 Metal-particle August 1986 Micromotion Ryd and linder 1989 Stress shielding Engh and Bobyn 1988 High fluid pressure Linder 1994Aspenberg and Van der Viis 1998Endotoxin Ragab et al 1999 Individual variations Matthews et al 2000 Sealed interface Schmalzried et al 1992 Various theories during the years regarding aseptic loosening Support for the above theory concerning effective joint space comes from the authors' own study on cemented acetabular components retrieved at autopsy (Schmalzried et al 1992b). Autopsy studies are important, since the well-functioning implant can be studied when no secondary changes such as osteoporosis and osteolysis have appeared.…”

Investigation of wear and wear particles from a UHMWPE/multi-walled carbon nanotube nanocomposite for total joint replacements

“…An improvement in the wear performance of conventional UHMWPE due to the addition of MWCNTs has also been reported [13]. However, it is known that not only the wear rates play a role in the biological reaction to wear debris but also factors such as the morphology, size, volume and composition of the wear particles are important [14] and [15]. Although this fact is a key factor in the success of the bearings, to the author's knowledge, there are no studies which use clinically relevant wear debris generated from this type of nanocomposites or assess the bioactivity of this type of wear particles.…”