Alpha-Tocopheryl Phosphate: a biomolecule for the modification of chemically treated Ti6Al4V alloy surfaces for antibacterial and anti-inflammatory purposes

The role of Vitamin E in human health has been widely studied since its discovery in 1922. In the beginning it was investigated just as nature's most potent lipid-soluble antioxidant, while now other properties have been discovered as its anti-bacterial, anti-inflammatory and anti-cancer activity. The scientific community has grown its interest in this compound over the past two decades, in particular the research in the biomedical field has brought the most convincing results as concern drug delivery systems, surface coatings, tissue engineering and regeneration, and wound healing. In this thesis, a water-soluble form of Vitamin E, the $\alpha$-tocopherol phosphate, associated with titanium surfaces will be discussed. Titanium and its alloys are the most used materials in the prosthetic implants field thanks to their fatigue resistance, stable chemical properties and good biocompatibility. However, problems as aseptic loosening and peri-implant infection may lead to implant removal. Therefore, the implant should have both osteogenic and antibacterial properties and actively take part in the confinement of the inflammatory response. The purpose of this thesis is to develop an anti-inflammatory and antibacterial surface by coupling a chemically treated Ti6Al4V surface with the above biomolecule for orthopedic and dental prosthetic devices.The titanium alloy (Ti6Al4V) disks used were firstly treated using a patented thermochemical surface treatment consisting of an acid etching in hydrofluoric acid in order to remove the native oxide. Following, a controlled oxidation in hydrogen peroxide at high temperature and under agitation was performed. The surface obtained presents a multi-scale topography characterized by a micro- and nano-roughness, (Ra = 0,25 ¿m) high density of hydroxyl groups, useful for potential functionalization, and a hydrophilic behavior (with a contact angle around 35¿). Moreover, the surface showed the ability to induce the precipitation of hydroxyapatite in vitro and an improved protein absorption. The treated titanium disks were then immersed in a calcium chloride solution to absorb Ca2+ ions and achieve a positively charged surface, thus creating a suitable surface where negatively charged alpha-tocopherol phosphate could create an electrostatic bond. The samples obtained were characterized to evaluate the presence of the vitamin on the surface by means of different physico/chemical techniques such as contact angle, Z potential, X-ray photoelectron spectroscopy (XPS), UV\Vis spectroscopy, FTIR analysis and Kelvin probe force microscopy. In addition, biological characterization was carried out by cytocompatibility and antibacterial tests.