The aim of this study is to investigate in vitro release of 17 beta-estradiol (E2), the potential drug to treat osteolysis, and the biological response to ultra-high molecular weight polyethylene loaded with E2 (UHMWPE-E2) wear debris. The osteoblasts (MC3T3-E1) and macrophages (RAW264.7) were co-cultured with UHMWPE-E2 wear debris via inversion culture technique, respectively. MTT, ALP and ELISA assay were employed to evaluate the cell proliferation, ALP activity and the expression of interleukin-6 (IL-6). In vitro E2 release included: initial burst release, celerity release and steady release. The E2 released steadily after 40 d and lasted more than 60 d. The E2 in UHMWPE-E2 wear debris promoted the proliferation and ALP activity of MC3T3-E1 cells at the high debris dosages of 8-10 mg. In particular, the UHMWPE-E2 wear debris inhibited the expression of IL-6 of osteoblasts at all dosages in the present study. RAW264.7 cells cultured with UHMWPE- E2 and UHMWPE wear debris exhibited large sizes about 100 mu m in diameter. The small size wear debris presented inside of cells indicated that the wear debris activated the phagocytosis of macrophages. The results indicated the E2 in UHMWPE-E2 would play a role in the treatment of the debris induced-osteolysis after artificial hip joint replacement. (c) 2012 Elsevier B.V. All rights reserved.