Mar Fernández

Synthesis and Biocompatibility of Hydroxyapatite in a Graphite Oxide Matrix

Though hydroxyapatite has the ability to promote bone growing, devices based on OHAp are mechanically weak and need to be reinforced for load bearing applications or in the manufacturing of scaffolds for bone regeneration. Graphite (Gr) could provide appropriate reinforcement properties to OHAp without being deleterious for the biocompatibility of the system. This paper describes an accelerated synthesis of the OHAp with ultrasonic agitation in the presence of functionalized graphite (GO). The toxicity of the Graphite and the GO-OHAp system is evaluated. GO-OHAp was produced by a wet chemical reaction involving CaCl2 and Na2HPO4. The calcium salt solution was added first and the solution sonicated for 1 hour, before repeating the operation with the phosphate solution. Biocompatibility was tested by using a primary cell culture of HOB (ECCAC). The disappearance of the maximum at 2q = 26.32º corresponding to the d002 plane of graphite and the appearance of the maximum at 2q = 13.2º in the XRD patterns is related with an expansion of the grapheme sheets from 0.34 nm to 0.59 nm and it has been used to assess the graphite oxidation. The OHAP on GO growing has been confirmed by the appearance of a broad peak centred at 2q = 31.5º and a sharpened peak at 2q = 26.0º characteristic of low crystalline apatites. Although the employed graphite can be considered biocompatible, cellular viability is significantly improved by the presence of apatite.

Mitochondrially targeted nanoparticles for the selective treatment of Head and Neck Squamous Cell Carcinoma

The aim of this work is the preparation of an active nanovehicle for the effective administration of α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative of α-TOS. These well-defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α-TOS significantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α-TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α-TOS administration.

Wollastonite-Poly(Ethylmethacrylate-Co-Vinylpyrrolydone) Nanostructured Materials: Mechanical Properties and Biocompatibility

Synthetic pseudowollastonite (psW) and a nanostructured copolymer made of a biostable component, Poly(ethylmethacrylate) (PEMA) and a bioresorbable component, vinylpyrrolidone (VP) are used in this work for the preparation of a new family of bone substitutes that allow osseointegration and mechanical stability. Composites are prepared by bulk polymerization of the desired composition in 15 mm diameter cylindrical plastic moulds. Polymerization was induced thermally at 50°C using 1wt% azobis(isobutyronitrile) (AIBN) as free-radical initiator. The moulds were filled to a height of 100 mm and 1 mm height discs were cut with a diamond saw. Specimens with a ceramic/polymer ratio 58/42, 33/67,17/83 and 0/100 were obtained. Compression stress in the range 39-59 MPa and elastic modulus between 2.64 and 4.14 GPa are obtained where the greater values correspond to the specimens prepared with a 60% ceramic load. Degradation in SBF produces a porous nanostructure in the polymeric component indicating microdomains of different solubility and the formation of an apatite-like layer on the surface of the wollastonite component. All the compositions assayed present a biocompatibility at least of the level or even superior than the Thermanox® control used.

Preparation of Targeting Vehicles for The Delivery of N-Bisphosphonates

Bisphosphonates (BP) are drugs currently administered orally to treat diseases characterised by an excessive bone resorption. Alternative and more efficient delivery routes and more potent compounds are being investigated. Three implantable delivery systems, which allow the controlled release of therapeutic agents from the device core, are examined in this paper. (4- (aminomethyl) benzene) bisphosphonic acid (ABBP) was incorporated on Ca8.8Na0.8(PO4)4.8(CO3)1.2(OH)0.4F1.6 particles by refluxing the powder in a 60 mmol suspension in acetone at 60°C for 5 hours. 4-aminophenyl acetic bisphosphonate monosodium salt (APBP) and 1- H-indole-3-acetic bisphosphonate monosodium (IBP) were loaded on Ca10(PO4)6(OH)1F1 ceramic bodies by stirring the ceramic bodies in 0.04M BP solutions. Injectable acrylic cements based on self-curing formulations of methyl methacrylate (MMA) and vitamin E were loaded with APBP and IBP. The incorporation of ABBP was confirmed by MAS-NMR spectroscopy. Modified powder shows two different phosphorous environments, the first one at 2.91 ppm can be assigned to the apatite base and the second one at 18.0 ppm has to be attributed to the phosphonic group of the ABBP. The IBP addition on ceramic surfaces did not decrease the number of osteoclast colonies and appeared to improve the performance of the HA as a surface for osteoblast culture. A therapeutic dosage of APBP and IBP can be achieved from acrylic cements that showed lack of toxicity and an increased cellular activity and proliferation.