AbstractThe aim of this work was to design, prepare and characterize novel composite materials with inherent antibacterial properties to be used in bone repair and bone regeneration applications. The project was developed in three stages, looking at novel filler materials initially and then investigating their use in two different types of scaffolds, namely soft hydrogels and hard cements.
The first part of the project dealt with the in vitro elucidation of the antibacterial activity and cytocompatibility of silver nanowires (AgNWs). These silver nanoparticles have been attracting increasing attention in comparison to other silver nanospecies due to their high aspect ratio that influences their thermal and electrical properties for use in flexible transparent conductive films (TCFs). Nevertheless, a limited number of papers have explored AgNWs antibacterial activity and eukaryotic toxicity. In this work, a polyol method, in presence or absence of carbon nanotubes (CNTs) has been used to guide the silver nanowires formation. Initially, the synthesised nanomaterials were fully characterized in terms of their physicochemical properties. Then, their toxicity, reactive oxygen species (ROS) formation and release of cytoplasmic proteins was studied against four different bacterial species and against three different mammalian cell types, to simulate different infection types and routes of exposure, respectively. Results showed that AgNWs, with similar characteristics, can be synthetized using either of the two synthetic methods, with no advantages imparted by the inclusion of CNTs in the synthetic process. Moreover, AgNWs were proven to be affective antibacterial agents acting via ROS formation and cellular membrane damage. Finally, we showed that AgNWs presented dose-dependent and time-dependent cytotoxicity following ROS formation in all the studied mammalian cell lines.
The second part of the project looked at applications of silver nanowires addressing the occurrence of infections as a complication following bone implant surgery. These infections can lead to destruction of the bone and consequently to an increased rate of treatment failure and delayed osseous-union. A chitosan-based hydrogel incorporating hydroxyapatite and AgNWs with potential bioactive, biocompatible properties and antibacterial properties was formulated. Physicochemical characterization, Ca/P deposition, silver release, antibacterial and cytocompatibility studies were carried out, and results suggested that the hydrogels herein developed present good bioactivity and biocompatible properties.
The third part focused on trying to solve some of the drawbacks related to the use of polymethyl methacrylate (PMMA) cements in vertebroplasty and total joint replacement: stiffness mismatch between the bone and the cement, high exothermic reaction temperature, leakage of toxic monomer and lack of antibacterial properties. In this part, we encapsulated AgNWs in PMMA bone cements with different concentrations of chitosan or methacryloyl-chitosan, to ensure a long lasting and increased release of Ag+ over time. Cytocompatibility, antibacterial and mechanical properties of the novel composite cements were investigated. This study suggested that the inclusion of CS/CSMCC (between 10 and 20%) and AgNWs (1%) in the existing commercial materials could provide bone cements with good results in terms of cytocompatibility combined with appropriate thermal, mechanical, and antibacterial properties. However, no advantages were shown by the inclusion of CSMCC over CS.
|Date of Award||Oct 2018|
|Supervisor||Marta Roldo (Supervisor), Gianluca Tozzi (Supervisor) & Eugen Barbu (Supervisor)|