Bone biomaterials for overcoming antimicrobial resistance: Advances in non-antibiotic antimicrobial approaches for regeneration of infected osseous tissue.

Eliminating bacterial infection and simultaneously providing a bioactive environment for bone growth during treatment of severe osteomyelitis is one of the greatest global challenges of modern orthopaedics. Additionally, antibiotic resistance has been deemed a major threat to public health resulting in 700,000 deaths globally per year. Therefore, the development of multifunctional non-antibiotic antimicrobial biomaterials that could locally fight highly resistant bacteria while providing a template for osseous tissue ingrowth would be a major breakthrough. Current research focuses on a myriad of technologies to create non-antibiotic antimicrobial pro-osteogenic biomaterials, ranging from the inherently antimicrobial, based on the effects of chemistry or topography, to the application of antimicrobial metal ions and oxides, polymers, or peptides, as well as the potential of utilising biofilm degrading enzymes, quorum sensing drugs, and bacteriophages. In this review, we have provided an overview of the currently available treatments for osteomyelitis with a special focus on novel, non-antibiotic based solutions currently being developed and their antimicrobial mechanisms. Finally, we will present discussion on future directions in the clinical translation of alternative biomaterial-based approaches to treat osteomyelitis.