IN-VIVO INFLAMMATORY RESPONSE TO POLYMETHYLMETHACRYLATE PARTICULATE DEBRIS - EFFECT OF SIZE, MORPHOLOGY, AND SURFACE-AREA

Particulate debris, including that from polymethylmethacrylate (PMMA) cement, is observed commonly in the membrane surrounding loose joint p rostheses. Such debris is assumed to cause an inflammatory response an d contributes to osteolysis and failure of the implant. A subcutaneous rat air-pouch model was used to assess quantitatively the in vivo eff ects of the size, morphology, and surface area of PMMA particles on th e acute inflammatory response. PMMA particles were divided into three groups. In Group A, mechanical grinding of cured bone cement produced irregularly shaped particles; Group B included spherical particles of PMMA powder (Simplex P); and Group C consisted of commercially prepare d spherical latex particles. All three groups had two size distributio ns: <20 mu m and 50-350 mu m. For a given mass or dose, the small, irr egularly shaped mechanically produced particles in Group A elicited a significantly greater inflammatory reaction than the large particles i n Group A, as expressed by the release of tumor necrosis factor (TNF), neutral metalloprotease (NMP), and prostaglandin E(2) (PGE(2)) and th e white blood cell (WBC) count within a 24-hour period. Similar findin gs were seen in Group B. Particles in Group C were used to compare the effect of absolute numbers of large and small particles and surface a rea. Large (10-126 mu m) spherical PMMA particles at a dose of 1.7 x 1 0(6) particles/ml caused a significantly higher inflammatory response, as measured by WBC count and production of NMP and PGE(2), than small (1-10 mu m) spheres at a dose of 4 x 10(6) particles/ml. However, the production of TNF in the rats was significantly increased with small particles (p < 0.05) at a concentration 4-fold less than that with the large particles (4 x 10(5) compared with 1.7 x 10(6) particles/ml). T his finding may reflect a different cellular mechanism for the TNF com ponent of the inflammatory response than is measured by WBC counts or by levels of PGE(2) and NMP. As the calculated surface area of the PMM A particles increased, a threshold level was reached, at which point t he inflammatory response increased dramatically. The size of particles has a role in the prolongation and intensity of the release of specif ic cytokines. The total surface area of the particles appeared to be a n important factor in determining the inflammatory response, as measur ed by WBC count, PGE(2), TNF, and NMP.