Mechanical Characterization and In Vitro Assay of Biocompatible Titanium Alloys.

Metals that come into contact with the body can cause reactions in the body, so biomaterials must be tested to avoid side effects. Mo, Zr, and Ta are non-toxic elements; alloyed with titanium, they have very good biocompatibility properties and mechanical properties. The paper aims to study an original Ti20Mo7ZrxTa system (5, 10, 15 wt %) from a mechanical and in vitro biocompatibility point of view. Alloys were examined by optical microstructure, tensile strength, fractographic analysis, and in vitro assay. The obtained results indicate very good mechanical and biological properties, recommending them for future orthopedic medical applications.

Electrochemical Analysis and In Vitro Assay of Mg-0.5Ca-xY Biodegradable Alloys.

In recent years, biodegradable Mg-based materials have been increasingly studied to be used in the medical industry and beyond. A way to improve biodegradability rate in sync with the healing process of the natural human bone is to alloy Mg with other biocompatible elements. The aim of this research was to improve biodegradability rate and biocompatibility of Mg-0.5Ca alloy through addition of Y in 0.5/1.0/1.5/2.0/3.0wt.%. To characterize the chemical composition and microstructure of experimental Mg alloys, scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), light microscopy (LM), and X-ray diffraction (XRD) were used. The linear polarization resistance (LPR) method was used to calculate corrosion rate as a measure of biodegradability rate. The cytocompatibility was evaluated by MTT assay (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) and fluorescence microscopy. Depending on chemical composition, the dendritic α-Mg solid solution, as well as lamellar Mg2Ca and Mg24Y5 intermetallic compounds were found. The lower biodegradability rates were found for Mg-0.5Ca-2.0Y and Mg-0.5Ca-3.0Y which have correlated with values of cell viability. The addition of 2-3 wt.%Y in the Mg-0.5Ca alloy improved both the biodegradability rate and cytocompatibility behavior.

Novel titanium-apatite hybrid scaffolds with spongy bone-like micro architecture intended for spinal application: In vitro and in vivo study.

Titanium alloy scaffolds with novel interconnected and non-periodic porous bone-like micro architecture were 3D-printed and filled with hydroxyapatite bioactive matrix. These novel metallic-ceramic hybrid scaffolds were tested in vitro by direct-contact osteoblast cell cultures for cell adhesion, proliferation, morphology and gene expression of several key osteogenic markers. The scaffolds were also evaluated in vivo by implanting them on transverse and spinous processes of sheep's vertebras and subsequent histology study. The in vitro results showed that: (a) cell adhesion, proliferation and viability were not negatively affected with time by compositional factors (quantitative MTT-assay); (b) the osteoblastic cells were able to adhere and to attain normal morphology (fluorescence microscopy); (c) the studied samples had the ability to promote and sustain the osteogenic differentiation, matrix maturation and mineralization in vitro (real-time quantitative PCR and mineralized matrix production staining). Additionally, the in vivo results showed that the hybrid scaffolds had greater infiltration, with fully mineralized bone after 6 months, than the titanium scaffolds without bioactive matrix. In conclusion, these novel hybrid scaffolds could be an alternative to the actual spinal fusion devices, due to their proved osteogenic performance (i.e. osteoinductive and osteoconductive behaviour), if further dimensional and biomechanical optimization is performed.

Synthetic open cell foams versus a healthy human vertebra: Anisotropy, fluid flow and µ-CT structural studies.

Commercial synthetic open-cell foams are an alternative to human cadaveric bone to simulate in vitro different scenarios of bone infiltration properties. Unfortunately, these artificial foams do not reproduce the anisotropic microstructure of natural bone and, consequently, their suitability in these studies is highly questionable. In order to achieve scaffolds that successfully mimic human bone, microstructural studies of both natural porous media and current synthetic approaches are necessary at different length scales. In this line, the present research was conducted to improve the understanding of local anisotropy in natural vertebral bone and synthetic bone-like porous foams. To attain this objective, small volumes of interest within these materials were reconstructed via micro-computed tomography. The anisotropy of the microstructures was analysed by means of both their main local histomorphometric features and the behaviour of an internal flow computed via computational fluid dynamics. The results showed that the information obtained from each of the micro-volumes of interest could be scaled up to understand not only the macroscopic averaged isotropic and/or anisotropic behaviour of the samples studied, but also to improve the design of macroscopic porous implants better fitting specific local histomorphometric scenarios. The results also clarify the discrepancies in the permeability obtained in the different micro-volumes of interest analysed. STATEMENT OF SIGNIFICANCE: A deep insight comparative study between the porous microstructure of healthy vertebral bone and that of synthetic bone-like open-cell rigid foams used in in vitro permeability studies of bone cement has been performed. The results obtained are of fundamental relevance to computational studies because, in order to achieve convergence values, the computation process should be limited to small computation domains or micro-volumes of interest. This makes the results specific spatial dependent and for this reason computation studies cannot directly capture the macroscopic average behaviour of an anisotropic porous structure such as the one observed in natural bones. The results derived from this study are also important because we have been able to show that the specific spatial information contained in only one healthy vertebra is enough to capture, from a geometric point of view, the same information of "specific surface area vs. porosity" - in other words, the same basic law - that can also be found in other human bones for different patients, even at different biological ages. This is an important finding that, despite the efforts made and the controversies formulated by other authors, should be studied more thoroughly with other bone species and tissues (healthy and/or diseased). Moreover, our results should help to understand that, with the extensive capabilities of current 3D printing technologies, there is an enormous potential in the design of biomimetic porous bone-like scaffolds for bone tissue engineering applications.

Analysis of bone cement distribution around fenestrated pedicle screws in low bone quality lumbosacral vertebrae.

PURPOSE: To study the exact distribution of bone cement around augmented fenestrated pedicle screws in both lumbar and sacral vertebrae of patients with low bone quality. METHODS: A total of 37 patients with instrumented lumbar fusion were investigated. 3D computed tomography virtual models of the injected cement and screws were obtained. The models were computed for their centroid (i.e. their average mass centre point), and their coordinates (x, y, z) were projected on their respective screw-transversal and screw-longitudinal planes for further analysis. RESULTS: The results showed better bone cement homogeneous distribution around the screws in lumbar (L4 and L5) than in sacral (S1) vertebrae. In the lumbar region, the centroids were transversally projected near the transversal centre of symmetry of the screws. On the other hand, in the sacral region, the cement flowed preferentially outside the centre of symmetry of the screws, into the sacral ala. CONCLUSIONS: The results confirm the different flow behaviours of bone cement in lumbar versus sacra vertebrae. The computer methodology followed in this study helps to understand the clinical monitoring observations and lays the foundations for better positioning of the screws and specific vertebrae-oriented screw designs.

Advantageous new conic cannula for spine cement injection.

STUDY DESIGN: Experimental study to characterize the influence of the cannula geometry on both, the pressure drop and the cement flow velocity established along the cannula. OBJECTIVE: To investigate how the new experimental geometry of cannulas can affect the extravertebral injection pressure and the velocity profiles established along the cannula during the injection process. SUMMARY OF BACKGROUND DATA: Vertebroplasty procedure is being used to treat vertebral compression fractures. Vertebra infiltration is favored by the use of suitable: (1) syringes or injector devices; (2) polymer or ceramic bone cements; and (3) cannulas. However, the clinical use of ceramic bone cement has been limited due to press-filtering problems. Thus, new approaches concerning the cannula geometry are needed to minimize the press-filtering of calcium phosphate-based bone cements and thereby broaden its possible applications. METHODS: Straight, conic, and combined conic-straight new cannulas with different proximal and distal both length and diameter ratios were drawn with computer-assisted design software. The new geometries were theoretically analyzed by: (1) Hagen-Poisseuille law; and (2) computational fluid dynamics. Some experimental models were manufactured and tested for extrusion in order to confirm and further advance the theoretical results. RESULTS: The results confirm that the totally conic cannula model, having proximal to distal diameter ratio equal 2, requires the lowest injection pressure. Furthermore, its velocity profile showed no discontinuity at all along the cannula length, compared with other known combined proximal and distal straight cannulas, where discontinuity was produced at the proximal-distal transition zone. CONCLUSION: The conclusion is that the conic cannulas: (a) further reduced the extravertebral pressure during the injection process; (b) showed optimum fluid flow velocity profiles to minimize filter-pressing problems, especially when ceramic cements are used; and (c) can be easily manufactured. In this sense, the new conic cannulas should favor the use of calcium phosphate bone cements in the spine. LEVEL OF EVIDENCE: N/A.

Iron oxide nanoparticles significantly enhances the injectability of apatitic bone cement for vertebroplasty.

STUDY DESIGN: Experimental study to characterize the setting and the cytocompatibility properties of apatitic bone cement. OBJECTIVE: To investigate the setting, flowing, and biocompatibility properties of new iron-modified calcium phosphate bone cements. SUMMARY OF BACKGROUND DATA: Vertebroplasty and kyphoplasty are efficient procedures for the treatment of painful vertebral compression fractures. Nowadays, calcium phosphate cements are used to treat these fractures mainly due to the similar bone apatitic phase formed after setting. However, clinicians have reported great difficulties in filling the vertebral bodies due to the high pressures needed to inject these materials. Thus, new approaches are needed to improve the initial flowing properties of these cements without affecting or even improving their short-term mechanical stability and their long-term in vivo cement transformation into bone tissue. METHODS: Cement setting times were measured by the Gillmore needles method. The evolution of the compressive strength accounted for the cement hardening process. Scanning Electron Microscopy followed the evolution of the cement microstructure with hardening. Radiograph diffraction analysis confirmed the evolution of the crystalline phases underlying the setting and the hardening processes. Injectability tests were performed by using syringes filled with bone cement and recording the evolution of the injection force needed to empty the syringe. Finally, the cytocompatibility was analyzed by culturing human epithelial cells onto the cements and evaluating both the relative cell viability and the adhesion cell density. RESULTS: The modification of the powder phase of an alpha-tricalcium phosphate cement with iron oxide nanopar-ticles significantly enhanced, at constant liquid to powder cement mixing ratio, the resulting cement injectability by lowering the extrusion force required for cement delivery. For example, 24 wt% iron oxide addition resulted in 83% of cement injected with an extrusion force lower than 25 N. In fact, the setting and the working times of the cement pastes increased with iron oxide addition. Moreover, the new cement pastes showed improved compressive strength in agreement with the crystalline microstructure evolved during hardening. However, iron modification did not produced cytotoxic cements as compare to nonmodified cements. CONCLUSION: It has been shown that the addition of iron oxide nanoparticles into the powder phase of an alpha-tricalcium phosphate based cement improved both, the initial injectability and maximum compressive strength of the cement without affecting their physico-chemical setting reactions and their cytocompatibility. These results could be further exploited by designing improved injectable apatitic cements with suitable mechanical properties and in vivo cement transformation ratios into bone tissue by incorporating phases creating porosity.

Modulation of porosity in apatitic cements by the use of alpha-tricalcium phosphate-calcium sulphate dihydrate mixtures.

Calcium phosphate bone cements are injectable biomaterials that are being used in dental and orthopaedic applications through minimally invasive surgery techniques. Nowadays, apatitic bone cements based on alpha-tricalcium phosphate (alpha-TCP) are of special interest due to their self-setting behaviour when mixed with an aqueous liquid phase. In this study, a new method to improve osteointegration of alpha-TCP-based cements is presented. This method consists in the modification of the cement's powder phase with different amounts of calcium sulphate dihydrate (CSD). The resulting hardening properties of the new biphasic cements are a combination between the progressive hardening due to the main alpha-TCP reactant and the progressive dissolution of the CSD phase, which render a porous material. It was observed that the maximum compressive strength of Biocement-H (45 MPa) decreased as the amount of CSD increased in the cement powder mixture ( approximately 30 MPa for 25 wt% of CSD). It was also observed that after complete dissolution of the CSD phase a porous apatitic structure appears with a mechanical compressive strength suitable for cancellous bone applications (10 MPa).