Eneko ELEZGARAY
defended his PhD on 25 November 2025 at IRCM
DESIGN OF A CALCIUM PHOSPHATE-BASED COMPOSITE CEMENT FOR THE TREATMENT OF BONE INFECTION
In front of the jury composed of:
Tristan FERRY, Infectiologue et coordinateur du CRIOAc, Lyon, rapporteur
Christophe DROUET, Directeur de recherche, CIRIMAT (UMR 5085), Toulouse, rapporteur
Gilles SUBRA, Professeur des Universités, IBMM, Montpellier, examinateur
Catherine FLACARD, Directrice compliance et innovation, Noraker, Lyon, examinatrice
Mikhael BECHELANY, Directeur de Recherche CNRS, IEM, Montpellier, directeur de thèse
Vincent CAVAILLES, Directeur de Recherche CNRS, IRCM, Montpellier, co-directeur de thèse
Abstract:
During life, bone tissue can be exposed to bacteria as a result of treatment for certain conditions or the insertion of implants, which can cause bone infections. Although treatment is possible, in recent years’ antibiotic-resistant bacterial strains have made treatment more complex. It appears that systemic treatment alone is often not effective enough due to the low vascularisation of bones. Synthetic bone substitutes, used for their good osteointegration properties and low cost, can be used as carriers for antibacterial agents for local delivery without replacing systemic treatments in the treatment of bone infections.
The aim of the work is to study the physicochemical and biological properties of a commercial calcium phosphatebased cement combined with two antibiotics, either alone or in combination, gentamicin and vancomycin, in order to be able to offer a cement with properties intermediate to those already on the market.
The first area focuses on characterising the physicochemical properties of cement after the addition of antibiotics, in order to understand the interactions between antibiotics and cement during setting. Tests are carried out using antibiotic formulations intended for research purposes, as well as references available in hospitals. The kinetics of release from the cement matrix have been studied. Finally, the antibacterial effect on planktonic or sessile (biofilm) bacteria was evaluated in vitro. A preliminary in vivo study was also conducted to assess the rate of cement degradation. The physicochemical properties obtained are comparable to those of calcium sulphate-based cement. The release of antibiotics guarantees a concentration several dozen times higher than the minimum inhibitory concentrations of strains representative of bone infections in the first few hours, and the maintenance of concentrations above these values for at least 49 days. A powerful
antibacterial effect has been demonstrated against planktonic and sessile bacteria, which is even more pronounced with the combination of the two antibiotics against methicillin resistant strains.
The second focus of the thesis aims to find an alternative to the use of antibiotics. To this end, the use of copper in various forms, the addition of copper nanoparticles, and the doping of a calcium phosphate phase were considered. However, the effect on the physicochemical properties of cement is too significant, and no antibacterial effect is observed with the addition of copper nanoparticles.
