In Vitro Biocompatibility Assessment and In Vivo Behavior of a New Osteoconductive ßTCP Bone Substitute.

OBJECTIVE: Beta-tricalcium phosphate (ßTCP) granules (OsproLife) exhibit a pure crystalline phase and a rough microporous surface for promoting cell adhesion and microsized intragranule porosity for improving wettability and resorption necessary for bone regeneration. OsproLife is a fully resorbable, space-maintaining, and osteoconductive synthetic material for the filling of bone defects. To asses OsproLife properties, a similar synthetic biomaterial, already on the market, has been chosen as reference: Cerasorb has the same chemical composition, but different crystal structure, surface morphology, and granule size. The aim of this study is to compare the properties of OsproLife and Cerasorb. METHODS: Chemical purity, composition and physical properties, in vitro cytotoxicity, and in vivo bone performance in a rabbit model were analyzed. ßTCP OsproLife granules (test) were compared with Cerasorb (control). Histological and µCT analyses were performed at 6, 12, and 56 weeks after implantation. RESULTS: ßTCP OsproLife and Cerasorb granules result to be both biocompatible and characterized by the same osteoconductivity and resorption rate. CONCLUSION: ßTCP OsproLife granules are a promising bone substitute for dental and orthopedic applications.

Characterization and cytocompatibility of a new injectable multiphasic bone substitute based on a combination of polysaccharide gel-coated OSPROLIFE(®) HA/TTCP granules and bone marrow concentrate.

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.

Set-up errors in head and neck cancer patients treated with intensity modulated radiation therapy: Quantitative comparison between three-dimensional cone-beam CT and two-dimensional kilovoltage images.

OBJECTIVES: 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. METHODS: 3D-CBCT and 2D-kV projections were acquired on 29 head-and-neck (H&N) 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. RESULTS: 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. CONCLUSION: A similar sensitivity to linear set-up errors was observed for 2D-kV and 3D-CBCT image guidance techniques in our H&N 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.

Intra-fraction setup variability: IR optical localization vs. X-ray imaging in a hypofractionated patient population.

BACKGROUND: The purpose of this study is to investigate intra-fraction setup variability in hypo-fractionated cranial and body radiotherapy; this is achieved by means of integrated infrared optical localization and stereoscopic kV X-ray imaging. METHOD AND MATERIALS: We analyzed data coming from 87 patients treated with hypo-fractionated radiotherapy at cranial and extra-cranial sites. Patient setup was realized through the ExacTrac X-ray 6D system (BrainLAB, Germany), consisting of 2 infrared TV cameras for external fiducial localization and X-ray imaging in double projection for image registration. Before irradiation, patients were pre-aligned relying on optical marker localization. Patient position was refined through the automatic matching of X-ray images to digitally reconstructed radiographs, providing 6 corrective parameters that were automatically applied using a robotic couch. Infrared patient localization and X-ray imaging were performed at the end of treatment, thus providing independent measures of intra-fraction motion. RESULTS: According to optical measurements, the size of intra-fraction motion was (median ± quartile) 0.3 ± 0.3 mm, 0.6 ± 0.6 mm, 0.7 ± 0.6 mm for cranial, abdominal and lung patients, respectively. X-ray image registration estimated larger intra-fraction motion, equal to 0.9 ± 0.8 mm, 1.3 ± 1.2 mm, 1.8 ± 2.2 mm, correspondingly. CONCLUSION: Optical tracking highlighted negligible intra-fraction motion at both cranial and extra-cranial sites. The larger motion detected by X-ray image registration showed significant inter-patient variability, in contrast to infrared optical tracking measurement. Infrared localization is put forward as the optimal strategy to monitor intra-fraction motion, featuring robustness, flexibility and less invasivity with respect to X-ray based techniques.

Uncertainties in lung motion prediction relying on external surrogate: a 4DCT study in regular vs. irregular breathers.

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 R(2) 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 R(2) 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 R(2), 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.