María Canillas

Targeting Neural Stem Cells with Titanium Dioxide Nanoparticles Coupled to Specific Monoclonal antibodies

Aiming to characterize the use of biomaterials in cancer therapy, we took advantage of the n-type semiconductor properties, which upon irradiation excite their electrons into the conduction band to induce photoelectrochemical reactions generating oxygen reactive species (ROS). Indeed, photoactivated TiO2 nanoparticles have been shown to kill in vitro either bacteria or tumor cells in culture following UV irradiation, as a consequence of the ROS levels generated; the killing was highly effective although devoid of specificity. In this report, we have directed the TiO2 nanoparticles to particular targets by coupling them to the monoclonal antibody (mAb) Nilo1, recognizing a surface antigen in neural stem cells within a cell culture, to explore the possibility of making this process specific. TiO2 nanoparticles generated with particular rutile/anatase ratios were coupled to Nilo1 antibody and the complexes formed were highly stable. The coupled antibody retained the ability to identify neural stem cells and upon UV irradiation, the TiO2 nanoparticles were activated, inducing the selective photokilling of the antibody-targeted cells. Thus, these data indicate that antibody-TiO2 complexes could be used to specifically remove target cell subpopulations, as demonstrated with neural stem cells. The possible applications in cancer therapy are discussed.

Physico-chemical properties of the Ti5O9 Magneli phase with potential application as a neural stimulation electrode

This work offers a description of the physico-chemical and electrochemical properties of one of the titanium-based Magneli phases, known as TinO2n-1, for its possible application as an electrode for neural tissue stimulation in neural disorders and Central Nervous System (CNS) injuries. Ti5O9 is one of the less-known Magneli phases that exhibits high electronic conductivity and high chemical and thermal inertness. The material, prepared in a reducing atmosphere by ceramic methods, is composed of a porous surface responsible for most of its properties. Chemical and physical features of the surface were studied with the aim of establishing a relationship between them and the surface electrochemistry. The chemical composition of the surface was studied by XRD and XPS. The topography was studied by AFM and the morphology of the outer side of a fracture was observed by SEM. The conductivity was measured by the four point method in DC finding extremely high values, 9500 S cm-1 at 37 °C. The study of the surface electrochemistry in contact with media, which simulate physiological conditions, was carried out by cyclic voltammetry and EIS. With these measurements the charge injection mechanism has been elucidated, and the charge storage capacity of the material has been determined, finding higher values than those reported for other ceramic electrodes. Finally, cell cultures realised with neural cells were obtained from the cerebral cortex of E18 Wistar rat embryos. They were observed after 4 and 10 DIV and helped in the determination of the biocompatibility of the material.

External and internal ontogenetic changes in the first rib

OBJECTIVES First ribs bear information about thorax morphology and are usually well preserved, compared to other ribs, in bone/fossil samples. Several studies have addressed ontogeny of the first rib by studying changes in bone microanatomy and rib morphology separately, but no studies have combined both approaches to study how internal and external changes covary during ontogeny. The aim of this project is to fill this gap in our knowledge. MATERIALS AND METHODS We applied 3D geometric morphometrics of sliding semilandmarks to 14 first ribs of Homo sapiens to quantify rib curvature and mid-shaft cross-section outline. Ontogenetic variation was addressed throughout a principal component analysis (PCA). Additionally, we made histological sections at the mid-shaft of the same ribs and studied tissue matrix composition and compartmentalization. Finally, we performed partial least squares (PLS) and regression analyses to study covariation between rib morphology and compartmentalization variables. RESULTS PCA shows that first ribs increase their curvature over the course of ontogeny and the rib midshaft becomes less rounded during ontogeny. In addition, the sternal end becomes more medially oriented during ontogeny and the relative head-tubercle distance becomes longer. Compartmentalization shows a decrease in the area occupied by mineralized tissues and an increase in the area occupied by non-mineralized tissues over the course of ontogeny, which covaries with mid-shaft cross-section shape. CONCLUSIONS Our results show detailed variation in rib morphology along with histological changes in bone tissue compartmentalization and, for the first time, the correlation between the two. This could be related to muscle attachments on the 1st rib and also to changes in breathing mode, from diaphragmatic in perinatals to pulmonary in adults, which could also have implications for understanding thorax evolution.

TiO2 surfaces support neuron growth during electric field stimulation

TiO2 is proposed here for the first time as a substrate for neural prostheses that involve electrical stimulation. Several characteristics make TiO2 an attractive material: Its electrochemical behaviour as an insulator prevents surface changes during stimulation. Hydration creates -OH groups at the surface, which aid cell adhesion by interaction with inorganic ions and macromolecules in cell membranes. Its ability to neutralize reactive oxygen and nitrogen species that trigger inflammatory processes confers biocompatibility properties in dark conditions. Here, physicochemical characterization of TiO2 samples and their surfaces was carried out by X-ray diffraction, X-ray photoelectronic emission spectroscopy, scanning electron microscopy, atomic force microscopy and by contact angle measurements. Its properties were related to the growth parameters and morphology of amphibian spinal neurons cultured on TiO2 samples. Neurons adhered to and extended neurites directly on TiO2 surfaces without pre-coating with adhesive molecules, indicating that the material permits intimate neuron-surface interactions. On TiO2 surfaces the distal tips of each extending neurite and the neurite shafts themselves showed more complex filopodial morphology compared with control cultures on glass. Importantly, the ability of TiO2 to support neuron growth during electric field exposure was also tested. The extent of growth and the degree of neurite orientation relative to the electric field on TiO2 approximated that on glass control substrates. Collectively, the data suggest that TiO2 materials support neuron growth and that they have potential utility for neural prosthetic applications incorporating electric field stimulation, especially where intimate contact of neurons with the material is beneficial.

Ti4O7 Used as Electrode in Biomedicine and for Electrochemical Study of Scavenging Mechanism

The biocompatibility of TiO2 is due to the activity that it shown in front of oxygen and nitrogen reactive species. Some authors suggest that the mechanism go through oxidation reduction reactions where changes of oxidation state in the Titanium and phases are involve. For this reason, Anderson-Magnelli phases could present scavenging activity. Moreover, these materials are use as electrodes and in that way are proposed as electrodes for study their scavenging mechanism by electrochemical methods.