Bioactivity Responses of Different Uhmwpe Particles from In-Vivo and In-Vitro Tests

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BIOACTIVITY RESPONSES OF DIFFERENT UHMWPE PARTICLES FROM IN-VIVO AND IN-VITRO TESTS YoungSoo Park,1,4 ShangYou Yang,2 Paul H. Wooley,2 Katharine Merritt,3*** Stephen Hsu,1 and Michael J. McNallan4 1 National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD 20899 2 Wayne State University, One South Hutzel Hospital, Detroit, MI 48201 3 U.S. Food and Drug Administration, 5600 Fishers Lane, Rockville MD 20857 4 University of Illinois at Chicago, 842 W. Taylor Street (M/C 246) Chicago, Illinois 60607

ABSTRACT This paper describes the results of bioactivity responses to different ultra high molecular weight polyethylene (UHMWPE) particles. Particles were produced by a wear tester using two different textures of steel counters, one with cross-hatched and the other with uni-hatched grooves. These two textured surfaces produced two distinct populations of wear particles. One is larger and more elongated (fibril shapes) than the other. The mean sizes and aspect ratios of the particles are in the ranges of 5 µm to 25 µm and about 1.5 to 3, respectively. These two distinct UHMWPE particles were examined through in-vitro and in-vivo tests. Macrophages RAW 264.7 and the murine air-pouch model of inflammation were employed to characterize the effect of the particle size and shape. Preliminary in-vivo tests results showed that more elongated and larger particles enhanced bio-reactions.

INTRODUCTION UHMWPE wear debris is generated from articulating surfaces in total joint replacements. The etiology of aseptic loosening remains unclear, but the generation of small wear particles from the prosthetic components is known to contribute to this pathology [1-3]. These particles are believed to activate macrophage and other inflammatory cells, induce release of soluble inflammatory mediators such as IL-1, TNF and IL-6, and subsequently cause osteolysis around implant components. Though UHMWPE particles retrieved from clinical cases are reported to have sizes ranging from sub-micron to mm, it has generally been believed that most of the debris are within the range of µm to sub-µm. One clinical study showed the mean sizes of particles in hip and knee joints were 0.5 ± 0.3 µm with a range of 0.1-10 µm, and, 1.7 ± 0.7 µm with range of 0.1 to 18 µm respectively [4, 5]. The role of particle size and shape in the bio-responses is still unclear, however, many publications, have suggested that smaller and elongated particles may have more stimulatory effects than larger ones [6-9]. If this is the case, it leads to the hypothesis that the various sizes and shapes of wear particles may have different activity in provoking cellular and cytokine responses. Thus, it is considered that there may be a threshold of stimulatory effects in the bioresponses. To test this hypothesis, it requires the generation of well-characterized particle populations in sufficient amounts of the different UHMWPE particles to evaluate the bioresponse. LL3.8.1

This paper addresses the possibility of generating different UHMWPE particle populations,