Douglas Wood

All Publications

• Alterations in the adhesion behavior of osteoblasts by titanium particle loading: Inhibition of cell function and gene expression BIORHEOLOGY Kwon, S. Y., Lin, T., Takei, H., Ma, Q. J., Wood, D. J., O'Connor, D., Sung, K. L. 2001; 38 (2-3): 161-183

  Abstract

  Total joint replacement prostheses are required to withstand corrosive environments and sustain millions of loading and articulation cycles during their term of implantation. Wear debris generation has been implicated as one of the primary causes of periprosthetic osteolysis and subsequent implant loosening in total joint replacements. Particulate debris consisting of metals, polyethylene, ceramics, and bone cement have each been shown to provoke a biological response in joint tissues. The major cell types within the interfacial granulomatous fibrous tissues consist of fibroblasts, macrophages, lymphocytes, and foreign-body giant cells. Osteoblasts are one of the principal cell types in the bone tissue adjacent to prostheses, maintaining physiologic bone remodeling through the balanced coordination of bone formation and resorption in concert with osteoclasts. To date the phenomenon of osteoblast phagocytosis of titanium particles has been suggested, but has not been sufficiently studied or confirmed. This study seeks to clarify the influence of titanium particles on osteoblast adhesion, deformability, proliferation, and gene expression profile. These studies were accomplished by performing biorheological testing, Northern blot analysis and RNase protection assay. The uptake of metallic particles by the osteoblast resulted in a particle-filament complex formation, which induced a series of variations in cell function. Understanding these variations is critical to expanding our knowledge of implant loosening and elucidating the nature of prosthetic joint failure. This study suggests that the impact of titanium particles on osteoblast function and subsequent implant loosening may have been previously underestimated.

  View details for Web of Science ID 000170067000009

  View details for PubMedID 11381173

• Titanium particles inhibit osteoblast adhesion to fibronectin-coated substrates JOURNAL OF ORTHOPAEDIC RESEARCH Kwon, S. Y., Takei, H., Pioletti, D. P., Lin, T., Ma, Q. J., Akeson, W. H., Wood, D. J., Sung, K. L. 2000; 18 (2): 203-211

  Abstract

  To illuminate the effect of titanium particles on osteoblast function, we compared the adhesion force of neonatal rat calvarial osteoblasts on fibronectin-coated glass after incubation with titanium particles (80% had diameters of less than 5 microm). The cells were incubated with the particles for 1.5-72 hours. Using a micropipette single-cell manipulation system, we showed that the adhesion force of the osteoblasts to fibronectin-coated glass (1.0 microg/ml) was significantly affected by the presence of particulate debris. The adhesion force of the cells incubated with titanium particles for less than 4 hours was not significantly affected by exposure to the particles; after 4 hours, however, it was significantly reduced relative to that of controls. Aspiration of particle-challenged osteoblasts into the micropipette demonstrated that the particles were not stripped from the cell surface and therefore confirmed that the osteoblasts had ingested them. During aspiration, the particles traveled through the cytoplasm rather than on the cell surface. When the osteoblasts were exposed to the particles and cytochalasin D, they exhibited much lower adhesion forces than did the controls or the cells exposed to titanium particles only; this indicates an important role of actin filaments in the osteoblastic response to particles. Staining for F-actin also indicated an influence of internalized titanium particulate on cytoskeletal arrangement and cell spreading. Furthermore, with standard Northern blotting techniques, levels of mRNA for collagen type I and fibronectin were significantly reduced as early as 4 hours after exposure to particles compared with levels in controls, and this effect continued to 72 hours. These data indicate that direct exposure of osteoblasts to titanium particles, which we propose to be ingested by the osteoblasts, can significantly decrease osteoblast adhesion force; this may lead to decreased cellular activity and gene expression of fibronectin and collagen type I in the presence of titanium wear debris.

  View details for Web of Science ID 000086949200006

  View details for PubMedID 10815820

• The cytotoxic effect of titanium particles phagocytosed by osteoblasts J Biomed Mater Res Pioletti DP, Takei H, Kwon SY, Wood D, Sung K-LP 1999; 46: 399-407
• Migration and healing of ligament cells under inflammatory conditions JOURNAL OF ORTHOPAEDIC RESEARCH Witkowski, J., Yang, L., Wood, D. J., Sung, K. L. 1997; 15 (2): 269-277

  Abstract

  It is well documented that the adult human medial collateral ligament has a functional healing response, whereas the anterior cruciate ligament does not. The differential healing responses of the medial collateral and anterior cruciate ligaments could be due to factors caused by different biological conditions and locations in vivo. In addition, different intrinsic properties of the constituent cells of these ligaments may contribute to their different healing abilities. Ligament healing follows an orderly process of hemorrhage, inflammation, proliferation, and remodeling. At the cellular level, healing involves a cell's detachment from and attachment to the matrix adjacent to the wound area, migration, and proliferation. This study sought to investigate whether, during migration, the responses of the medial collateral and anterior cruciate ligament fibroblasts are intrinsically different under the same inflammatory conditions. Human medial collateral and anterior cruciate ligament fibroblast cells were cultured, and in vitro wounds were simulated by streaking the cells with an inoculating loop, creating a cell-free area. The migration of the cells into this gap, thus filling the cell-free area, was observed. Two sets of experiments were conducted; one varied the wound width and the other added the inflammatory factors tumor necrosis factor-alpha, complement C5a, and lipopolysaccharide. As the width of the wound increased, the rate of recovery decreased for both types of ligament cells (slope: anterior cruciate ligament, 0.13 hour/micron and medial collateral ligament, 0.10 hour/micron). Also, the three inflammatory factors used all inhibited the recovery rates of both ligaments to ones that were 1.4-2.3 times slower than controls. However, in both sets of experiments, the anterior cruciate ligament fibroblasts were more sensitive to inflammatory factors, and the medial collateral ligament fibroblasts had faster recovery rates (anterior cruciate ligament, 1.2-3.4 times slower than rates for medial collateral ligament fibroblasts, excluding those under lipopolysaccharide treatment). The results showed that medial collateral and anterior cruciate ligament fibroblasts responded differently under the same inflammatory conditions. This may suggest that these differences in intrinsic properties contribute to their different healing responses and abilities.

  View details for Web of Science ID A1997XA75300016

  View details for PubMedID 9167631

• Quantification of adhesiveness of osteoblasts to titanium surfaces in vitro by the micropipette aspiration technique. Tissue engineering Nugiel, D. J., Wood, D. J., Sung, K. L. 1996; 2 (2): 127-140

  Abstract

  For osseointegration to occur at a biomaterial surface implanted in tissue, osteoblasts must first adhere to the surface and subsequently lay down a framework of submatrix proteins and mineral. Thus the adhesion force of an osteoblast to a surface can serve as a measure of its biocompatibility during the first hours after implantation. This study used the micropipette aspiration technique to quantify the adhesion force of individual Ost-6 neonatal rat calvarial osteoblasts interacting with smooth, rough, fibronectin (FN)-coated, and hydroxyapatite (HA)-coated commercially pure titanium surfaces. Individual cellular adhesion forces ranged from 2 to 320 mdyn and were proportional to the time allowed to adhere (seeding time, 15-120 min) and adsorbed FN coating concentration (5-20 microg/ml). For the 60 min seeding time, osteoblasts adhered 80% more strongly to 5 microg/ml FN-coated titanium than to smooth uncoated titanium, due to specific affinity of the alpha(v)beta(1) transmembrane integrin for the FN molecule. Average adhesion force on plasma sprayed HA-coated titanium was only 40% as high as the uncoated surface, indicating that the osteoconductive effects of HA were not evident in the first 60 min of adhesion. There was no difference in adhesion force between the uncoated smooth and rough titanium surfaces for the 60 min seeding time. The uncoated and FN-coated titanium surfaces had the same average cell-surface contact angle used to assess the degree of cell flattening on the titanium surface. This indicated that osteoblasts formed equal quantities of cell-substrate bonds to the two surfaces but with very different adhesion forces, thus osteoblast affinity for the titanium surfaces was expressed in higher individual cell-substrate bond forces.

  View details for DOI 10.1089/ten.1996.2.127

  View details for PubMedID 19877935