Radiotherapy to the head and neck region negatively influences the osseointegration and survival of dental implants. The effects of cobalt 60 (60Co) ionizing radiation and the impact of backscatter rays were investigated on human mesenchymal stem cells cultured on titanium surfaces. Bone marrow‐derived human mesenchymal stem cells were seeded on titanium (Ti), fluoride‐modified titanium (TiF), and tissue culture plastic. Cells were exposed to ionizing γ‐radiation in single doses of 2, 6, or 10 Gy using a 60Co source. Density and distribution of cells were evaluated using confocal laser‐scanning microscopy, 21 d post‐irradiation. Lactate dehydrogenase concentration and the levels of total protein and cytokines/chemokines were measured in the cell‐culture medium on days 1, 3, 7, 14, and 21 post‐irradiation. Unirradiated cells were used as the control. Irradiation had no effect on cell viability, collagen and actin expression, or cell distribution, but induced an initial increase in the secretion of interleukin (IL)‐6, IL‐8, monocyte chemotactic protein 1 (MCP‐1), and vascular endothelial growth factor (VEGF), followed by a decrease in secretion after 3 or 7 d. Irradiation resulted in secretion of a lower amount of all analytes examined compared with controls on day 21, irrespective of radiation dose and growth surface. Backscattering from titanium did not influence the cell response significantly, suggesting a clinical potential for achieving successful osseointegration of dental implants placed before radiotherapy.
Objective The influence of radiation backscatter from titanium on DNA damage and migration capacity of human osteoblasts (OBs) and mesenchymal stem cells (MSCs) may be critical for the osseointegration of dental implants placed prior to radiotherapy. In order to evaluate effects of radiation backscatter, the immediate DNA damage and migration capacity of OBs and MSCs cultured on titanium or plastic were compared after exposure to ionizing irradiation. Materials and methods Human OBs and MSCs were seeded on machined titanium, moderately rough fluoride-modified titanium, or tissue culture polystyrene, and irradiated with nominal doses of 2, 6, 10, or 14 Gy. Comet assay was performed immediately after irradiation, while a scratch wound healing assay was initiated 24 h post-irradiation. Fluorescent live cell imaging documented the migration. Results DNA damage increased with higher dose and with backscatter from titanium, and MSCs were significantly more affected than OBs. All doses of radiation accelerated the cell migration on plastic, while only the highest dose of 10 Gy inhibited the migration of both cell types on titanium. Conclusions High doses (10 Gy) of radiation inhibited the migration capacity of both cell types on titanium, whereas lower doses (2 and 6 Gy) did not affect the migration of either OBs or MSCs. Clinical relevance Fractionated doses of 2 Gy/day, as distributed in conventional radiotherapy, appear not to cause severe DNA damage or disturb the migration of OBs or MSCs during osseointegration of dental implants.
In head and neck cancer patients receiving dental implants prior to radiotherapy, backscatter from titanium increases the radiation dose close to the surface, and may affect the osseointegration. The dose-dependent effects of ionizing radiation on human osteoblasts (hOBs) were investigated. The hOBs were seeded on machined titanium, moderately rough fluoride-modified titanium, and tissue culture polystyrene, and cultured in growth- or osteoblastic differentiation medium (DM). The hOBs were exposed to ionizing γ-irradiation in single doses of 2, 6 or 10 Gy. Twenty-one days post-irradiation, cell nuclei and collagen production were quantified. Cytotoxicity and indicators of differentiation were measured and compared to unirradiated controls. Radiation with backscatter from titanium significantly reduced the number of hOBs but increased the alkaline phosphatase activity in both types of medium when adjusted to the relative cell number on day 21. Irradiated hOBs on the TiF-surface produced similar amounts of collagen as unirradiated controls when cultured in DM. The majority of osteogenic biomarkers significantly increased on day 21 when the hOBs had been exposed to 10 Gy, while the opposite or no effect was observed after lower doses. High doses reinforced with backscatter from titanium resulted in smaller but seemingly more differentiated subpopulations of osteoblasts.
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