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Aseptic loosening of prosthetic arthroplasty is the most common reason for implant failure in adult orthopaedic reconstruction. At the interface of aseptic loosened prostheses, there is an abundance of particleactivated macrophages and other inflammatory cells. The role of these particleladen macrophages in the osteogenic arm of the remodeling skeleton in this pathological condition is poorly understood. Molecular signaling by mesenchymal cells and mononuclear inflammatory cells residing in the interfacial tissues between bone and cement or prosthetic material of aseptically loosened joint prostheses was studied using in situhybridization and immunohistochemical techniques. We found that a range of collagenous and noncollagenous matrix proteins, including osteopontin, osteocalcin, bone sialoprotein, and type I collagen, were produced in the periprosthetic tissue by foamy macrophages, as well as nearby osteogenic cells. The former accumulated in profusion in the three zones of interfacial tissues: pseudomembranous, fibrous, and osseous. Spindle mesenchymal cells in the fibrous zone failed to express any of the osteogenic mRNAs or proteins sought. The expression of bonerelated genes and proteins by foamy macrophages at the interface of an aseptic loosened prosthesis may contribute to the disturbance of bone remodeling at this site. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 65A: 109–117, 2003

Various surface modifications have been applied to titanium alloy Ti6Al4V implants, in an attempt to enhance osseointegration; crucial for ideal prosthetic fixation. Despite the numerous studies demonstrating that peptidemodified surfaces influence in vitrocellular behavior, there is relatively little data reporting their effects on bone remodeling. The objective of this article was to examine the effects of chemically modifying Ti6Al4V surfaces with a common RGD sequence, a 15residue peptide containing GRGDSP glycinearginineglycineaspartateserineproline, on the modulation of bone remodeling. The expression of proteins known to be associated with osseous matrix and bone resorption were studied during the growth of human bonederived cells HBDC on these peptidemodified surfaces. HBDC grown for 7 days on RGD surfaces displayed significantly increased levels of osteocalcin, and procollagen Iα1 mRNAs, compared with the production by HBDC grown on the native Ti6Al4V. A pattern that was also reflected at the protein levels for osteocalcin, type I collagen, and bone sialoprotein. Moreover, HBDC grown for 7 and 14 days on RGDmodified Ti6Al4V expressed significantly higher level of osteoclast differentiation factors and lower levels of osteoprotegerin and IL6 proteins compared with other surfaces tested. These results suggest that different chemical treatments of implant material Ti6Al4V surface result in differential bone responses, not only their ability to form bone but also to stimulate osteoclastic formation. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 105–113, 2003

Poor cell adhesion to orthopaedic and dental implants may result in implant failure. Cellular adhesion to biomaterial surfaces primarily is mediated by integrins, which act as signal transduction and adhesion proteins. Because integrin function depends on divalent cations, we investigated the effect of magnesium ions modified bioceramic substrata Al2O3Mg2 on human bonederived cell HBDC adhesion, integrin expression, and activation of intracellular signalling molecules. Immunohistochemistry, flow cytometry, cell adhesion, cell adhesion blocking, and Western blotting assays were used. Our findings demonstrated that adhesion of HBDC to Al2O3Mg2was increased compared to on the Mg2free Al2O3. Furthermore, HBDC adhesion decreased significantly when the fibronectin receptor α5β1 and β1integrins were blocked by functional blocking antibodies. HBDC grown on the Mg2modified bioceramic expressed significantly enhanced levels of β1, α5β1, and α3β1integrins receptors compared to those grown on the native unmodified Al2O3. Tyrosine phosphorylation of intracellular integrindependent signalling proteins as well as the expression of key signalling protein Shc isoforms p46, p52, p66, focal adhesion kinase, and extracellular matrix protein collagen type I were significantly enhanced when HBDC were grown on Al2O3Mg2compared to the native Al2O3. We conclude that cell adhesion to biomaterial surfaces is probably mediated by α5β1 and β1integrin. Cationpromoted cell adhesion depends on 5β1 and β1integrins associated signal transduction pathways involving the key signalling protein Shc and results also in enhanced gene expression of extracellular matrix proteins. Therefore, Mg2supplementation of bioceramic substrata may be a promising way to improve integration of implants in orthopaedic and dental surgery. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 175–184, 2002

Summary The passage of tissue fluid through cortical bone has been investigated using radioactively labelled macromolecules as markers. The results suggest that in the cortex of young rabbit femur the movement of tissue fluid is in the same net direction as blood, mainly from the endosteal to the periosteal surface.