It has been suggested that surface modification with a thin hydroxyapatite (HA) coating enhances the osseointegration of titanium implants. However, there is insufficient information about the biological processes involved in the HA-induced response. This study aimed to investigate the inflammatory cell response to titanium implants with either amorphous or crystalline thin HA. Human mononuclear cells were cultured on titanium discs with a machined surface or with a thin, 0.1 μm, amorphous or crystalline HA coating. Cells were cultured for 24 and 96 h, with and without lipopolysaccharide (LPS) stimulation. The surfaces were characterized with respect to chemistry, phase composition, wettability and topography. Biological analyses included the percentage of implant-adherent cells and the secretion of pro-inflammatory cytokine (TNF-α) and growth factors (BMP-2 and TGF-β1). Crystalline HA revealed a smooth surface, whereas the amorphous HA displayed a porous structure, at nano-scale, and a hydrophobic surface. Higher TNF-α secretion and a higher ratio of adherent cells were demonstrated for the amorphous HA compared with the crystalline HA. TGF-β1 secretion was detected in all groups, but without any difference. No BMP-2 secretion was detected in any of the groups. The addition of LPS resulted in a significant increase in TNF-α in all groups, whereas TGF-β1 was not affected. Taken together, the results show that thin HA coatings with similar micro-roughness but a different phase composition, nano-scale roughness and wettability are associated with different monocyte responses. In the absence of strong inflammatory stimuli, crystalline hydroxyapatite elicits a lower inflammatory response compared with amorphous hydroxyapatite.

The inflammatory response to titanium and hydroxyapatite (HA)-coated titanium in living tissue is controlled by a number of humoral factors, of which monocyte chemoattractant protein-1 (MCP-1) has been specifically linked to the recruitment of monocytes. These cells subsequently mature into tissue-bound macrophages. Macrophages adhering to the proteins adsorbed at the implant surface play a pivotal role in initiating the rejection or integration of the foreign material. Despite this, little is known about the initial inflammatory events that occur in soft tissues following the implantation of titanium and HA-coated titanium implants. In this study, circular discs of commercially pure titanium (c.p. Ti) with either a thin crystalline HA coating or amorphous HA coating or uncoated were implanted subcutaneously into rats. The implants were retrieved after 24 and 72 h. The lactate dehydrogenase (LD) activity, DNA content, expression of MCP-1, interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), as well as monocyte and polymorphonuclear granulocyte counts in the exudate surrounding the implants were analyzed. There were significantly higher DNA and LD levels around the titanium implants at 24 h compared with HA-coated titanium. A rapid decrease in MCP-1 levels was observed for all the implants over the period of observation. No statistically significant differences were found between the two HA-coated implants. Our results suggest a difference in the early soft-tissue response to HA-coated implants when compared with titanium implants, expressed as a downregulation of inflammatory cell recruitment. This suggests that thin HA coatings are promising surfaces for soft tissue applications.

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Chronic obstructive pulmonary disease (COPD) still poses a formidable challenge to patients and clinicians alike. A fixed-dose dry powder combination inhaler, Seretide/Advair, containing salmeterol and fluticasone, is licensed in the European Community for the treatment of moderate to severe COPD in the strength of 50/500 microg twice daily (BID). Several studies have investigated the effects of this combination and show improved forced expiratory volume in 1 s (FEV(1)), quality of life, and a decrease of exacerbations. Most of the studies have run for less than 1 year. The aim of this investigator-initiated, independent study was to elucidate if the combination containing 50 microg of salmeterol and 250 microg of fluticasone BID could be shown to have the same beneficial effect as the higher dosage, and if the effect could be sustained over time.

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