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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.

Since the development of the posterior lumbar interbody fusion (PLIF) and anterior approach for anterior cervical discectomy and fusion (ACDF) many different fusion substrates such as grafts and devices, have been explored. This includes autografts, allografts, and interbody spacers made from polyether-ether-ketone (PEEK), porous tantalum and titanium.In an attempt to combine only the advantages from both the PEEK and titanium interbody devices, a novel type of PEEK titanium composite (PTC) interbody fusion device has been developed. This device combines a PEEK core with titanium alloy endplates made from a novel 3-dimensional (3D) titanium mesh (Ti6Al4V) to potentially enable a better bone apposition and ingrowth while enabling imaging of the fusion site.This chapter covers how the novel PTC interbody devices are manufactured, which applications the PTC technology have currently been applied to, and how the mechanical properties of the interbody devices that employ the PTC technology compare to that of standard PEEK devices. In addition, the surface topography of the Ti6Al4V endplates will be discussed alongside a presentation of several in vitro and in vivo studies that have been completed for the PTC technology. Specifically, two in vitro studies will be presented showing the effect of each of the structural components (PEEK, Ti6Al4V) on the proliferation and differentiation of immature and mature osteoblasts. Furthermore, two in vivo studies will illustrate the effect of the structural components (PEEK, Ti6Al4V) on bone ingrowth/ongrowth and biocompatibility in a rabbit model, and the effect of a clinical PTC device in an ovine lumbar fusion model. Lastly, a discussion will summarize the presented studies and make the case for the PTC technology as a new standard for interbody devices in spine fusion.

Beta-tricalcium phosphate (βTCP) 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.Chemical purity, composition and physical properties, in vitro cytotoxicity, and in vivo bone performance in a rabbit model were analyzed. βTCP OsproLife granules (test) were compared with Cerasorb (control). Histological and μCT analyses were performed at 6, 12, and 56 weeks after implantation.βTCP OsproLife and Cerasorb granules result to be both biocompatible and characterized by the same osteoconductivity and resorption rate.βTCP OsproLife granules are a promising bone substitute for dental and orthopedic applications.

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.