Research in our labs - CERAMIC BIOMATERIALS AND PHAGOTHERAPY IN OSTERO-ARTICULAR SURGERY

For several decades, calcium phosphate-based ceramics have been used as substitutes for bone defects in osteoarticular surgery. Their mineral composition is similar to that of bone, and they feature very good bioactivity since these biocompatible compounds induce the same biological responses as bone. The purity, stoichiometry¹ , chemical composition and granular characteristics of ceramic powders are crucial parameters for obtaining devices with optimal physical and biological properties. These materials are available as injectable cements, granules and dense or macroporous solids. Calcium phosphate granules are generally selected for conventional bone filling.

At the CERAMATHS laboratory, synthesis parameters are optimized to produce a product that meets surgical implant standards. However, implanted prostheses and bone substitutes can be contaminated and give rise to the formation of bacterial biofilms. These biofilms are responsible for osteoarticular infections and their recurrence. What's more, the heterogeneity of a biofilm enables bacterial synergies that improve its resistance to certain stress factors, including antibiotics. To combat infectious biofilms, ceramic materials can be spiked with bacteriophages, which will be progressively released and target bacterial agents.

¹Stoichiometry is a calculation used to analyze the quantities of reactants and products involved in a chemical reaction.

Bacteriophages are viruses that have the particularity of infecting only bacteria according to a specific recognition mode. They are therefore incapable of infecting animal and plant cells. Phage therapy is the use of lytic bacteriophages to treat certain infectious diseases of bacterial origin, such as nosocomial infections caused by multi-resistant bacteria. Indeed, the high incidence of multi-drug-resistant (MDR) bacteria is bringing us closer to what could be a post-antibiotic era in medicine. As a result, the properties and therapeutic potential of phages have been rediscovered and have recently become an area of active interest, showing great promise as alternative treatments or in combination with antibiotic therapy. To this end, phage therapy by functionalization of bone substitutes is proposed by the CERAMATHS laboratory in collaboration with the UGSF CNRS8576 bacterial envelope genetics team. Initial studies show that bacteriophage-loaded ceramic devices can be used as a prophylactic treatment. Indeed, calcium phosphate-based ceramic materials can be doped with a cocktail of phages enabling the desorption of several phages in the bacterial proliferation medium leading to the lysis of different bacterial species simultaneously.

Our work also shows that phages loaded on ceramic material prevent biofilm initiation and allows the complete destruction of a preformed 24h Staphylococcus aureus biofilm after 96 hours of incubation with our bacteriophage-doped ceramic device. Moreover, phages loaded onto ceramic pellets do not affect cell proliferation and protect osteoblasts from S. aureus infection in vitro. Our phage-doped TCP materials could be a good prosthetic device to limit bacterial infections in osteoarticular surgery and, by protecting against such infections, allow proliferation and colonization of osteoblastic cells on the inorganic support after implantation. However, it is essential to use a phage or phage cocktail targeted against the germs at the patient's infection site. As the phage/bacterial species relationship is specific, it is important to have identified the etiological agents beforehand, and this remains an unresolved problem, making this method a curative rather than a preventive therapy to date