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The purpose of this study was to examine the in vitro cytocompatibility of a novel injectable multiphasic bone substitute (MBS) based on polysaccharide gel-coated OSPROLIFE(®) hydroxyapatite (HA)/tetracalcium phosphate (TTCP) granules combined with bone marrow concentrate (BMC). Polysaccharide gel-coated granules loaded in syringe were combined with BMC diluted in ionic crosslinking solution. The product was then maintained in culture to investigate the cytocompatibility, distribution, and osteogenic differentiation function of cells contained in the BMC. The in vitro cytocompatibility was assessed after 0, 24, and 96 h from the injectable MBS preparation using the LIVE/DEAD(®) staining kit. The results highlighted that cells remained viable after combination with the polysaccharide gel-coated granules; also, viability was maintained over time. The distribution of the cells in the product, observed using confocal microscopy, showed viable cells immersed in the polysaccharide gel formed between the granules after ionic crosslinking. The mesenchymal stromal cells (MSC) contained in the injectable MBS, the basic elements for bone tissue regeneration, were able to differentiate toward osteoblasts, producing an osteogenic matrix as evidenced by alizarin red-s (AR-S) staining. In conclusion, we found that the injectable MBS may have the potential to be used as a bone substitute by applying a "one-step" procedure in bone tissue engineering applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 894-902, 2016.

To compare the patient set-up error detection capabilities of three-dimensional cone beam computed tomography (3D-CBCT) and two-dimensional orthogonal kilovoltage (2D-kV) techniques.3D-CBCT and 2D-kV projections were acquired on 29 head-and-neck (HN) patients undergoing Intensity Modulated Radiotherapy (IMRT) on the first day of treatment (time 0) and after the delivery of 40 Gy and 50 Gy. Set-up correction vectors were analyzed after fully automatic image registration as well as after revision by radiation oncologists. The dosimetric effects of the different sensitivities of the two image guidance techniques were assessed.A statistically significant correlation among detected set-up deviations by the two techniques was found along anatomical axes (0.60 ρ 0.72, p 0.0001); no correlation was found for table rotation (p = 0.41). No evidence of statistically significant differences between the indications provided along the course of the treatment was found; this was also the case when full automatic versus manually refined correction vectors were compared. The dosimetric effects analysis revealed slight statistically significant differences in the median values of the maximum relative dose to mandible, spinal cord and its 5 mm Planning Organ at Risk Volume (0.95%, 0.6% and 2.45%, respectively), with higher values (p 0.01) observed when 2D-kV corrections were applied.A similar sensitivity to linear set-up errors was observed for 2D-kV and 3D-CBCT image guidance techniques in our HN patient cohort. Higher rotational deviations around the table vertical axis were detected by the 3D-CBCT with respect to the 2D-kV method, leading to a consistent better sparing of organs at risk.

This paper examines the uncertainty in estimating lung motion from external surrogates for lung cancer patients with regular and irregular breathing. 4DCT data sets were analyzed using a template matching algorithm to track the spatial movement of vessel bifurcations in 12 patients. The detected internal movement of features in 3D was retrospectively synchronized with the RPM surrogate signal, and the correlation index R2 and the prediction error were computed. Patients were classified into two groups depending on the presence or not of irregularities in their breathing pattern. Peak-to-peak values of feature motion in the SI direction ranged from 0.8 mm (upper lung) to 25.3 mm (lower lung). Some patients exhibited large motion also in the latero-lateral (10.6 mm) and anterior-posterior (12.2 mm) directions. The median ± quartile of R2 in SI direction was 0.89 ± 0.09. Prediction error values were up to 4.2 mm (95th percentile) with a maximum value of 4.9 mm. Statistical differences between regular and irregular breathers were found for R2, while prediction error depended only on the range of motion. This study is relevant for image guided radiotherapy methods that rely on external surrogates to monitor motion.