ABSTRACT
AIM: Radiotherapy is associated with cell depletion and loss of blood supply, which are linked to compromised bone healing. However, the molecular events underlying these effects at the tissue-implant interface have not been fully elucidated. This study aimed to determine the major molecular mediators associated with compromised osseointegration due to previous exposure to radiation. MATERIALS AND METHODS: Titanium implants were placed in rat tibiae with or without pre-exposure to 20 Gy irradiation. Histomorphometric, biomechanical, quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay analyses were performed at 1 and 4 weeks after implantation. RESULTS: The detrimental effects of irradiation were characterized by reduced bone-implant contact and removal torque. Furthermore, pre-exposure to radiation induced different molecular dysfunctions such as (i) increased expression of pro-inflammatory (Tnf) and osteoclastic (Ctsk) genes and decreased expression of the bone formation (Alpl) gene in implant-adherent cells; (ii) increased expression of bone formation (Alpl and Bglap) genes in peri-implant bone; and (iii) increased expression of pro-inflammatory (Tnf) and pro-fibrotic (Tgfb1) genes in peri-implant soft tissue. The serum levels of pro-inflammatory, bone formation and bone resorption proteins were greater in the irradiated rats. CONCLUSIONS: Irradiation causes the dysregulation of multiple biological activities, among which perturbed inflammation seems to play a common role in hindering osseointegration.
ABSTRACT
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-ß1). 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-ß1 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-ß1 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.
Subject(s)
Dental Implants , Durapatite/chemistry , Inflammation , Lipopolysaccharides/chemistry , Animals , Bone Morphogenetic Protein 2/metabolism , Cell Line , Coated Materials, Biocompatible/chemistry , Crystallization , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Humans , Leukocytes, Mononuclear/cytology , Materials Testing , Mice , Monocytes/cytology , Osseointegration/drug effects , RAW 264.7 Cells , Surface Properties , Titanium/chemistry , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
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.
