Functionalization of Ti6Al4V surface with a peptoid for antibacterial purposes

The increasing resistance of bacteria to conventional antibiotics and the limited therapeutic efficacy of current alternative antimicrobial agents have propelled society to a post-antibiotic era. Dental implants have been the focus of extensive investigation in recent years with the fundamental aim of preventing implant failure and antimicrobial resistance. The principal etiologic factor that causes inflammation condition of peri-implant tissues is the oral biofilm in the trans-mucosal region, particularly around the collar and abutment of the implant, which significantly differs from the interface between the gingiva and natural teeth. Antimicrobial peptides (AMPs) have gained attention as possible alternative drugs thanks to their advantages, including the ability to hamper the development of resistance by pathogens and their high selectivity. However, AMPs have shown clinical issues (mainly their enzymatic degradation) that limit their possibility of being put on the market with success. Peptoids are a group of synthetic and bio-mimetic biomolecules, also known as poly-N-substituted glycines, whose success is in continuous growth. These compounds have been investigated as novel biologically active thanks to their important biochemical properties, including structural diversity compared to peptide, resistance to proteolytic degradation, reduced immunogenicity, enhanced cellular permeability, and ability to fold into higher-order nanostructures. This thesis aims to investigate the behavior of a chemically treated (CT) titanium surface, functionalized with a peptoid, to promote adhesion and proliferation of gingival fibroblast while simultaneously reducing bacterial adhesion. A synthesized peptoid GN2-Npm9 was chemically adsorbed on the titanium alloy Ti6Al4V (ASTM B348 Grade 5) and its properties were investigated. Firstly, surface characterization was conducted using the XPS analysis, zeta potential titration curves, and confocal microscopy. The results confirmed the homogeneous dispersion and electrostatic adsorption of the peptoid on the CT surface, which has a negative surface charge at pH 7.4. Biological tests were performed on CT specimens and CT_GN2-Npm9 specimens: a test was conducted on cultured human mesenchymal stem cells to evaluate the cytocompatibility, while the antimicrobial properties were studied against oral microbiota from healthy and pathological patients. The biological evaluations confirmed that CT_GN2-Npm9 surfaces emerge as a promising combination of nano-topography and bioactive compounds. They exhibit a selective ability to hinder bacterial infection while preserving the cells' capacity to colonize the device, making them particularly attractive for potential biomedical applications.