Orthopaedic device related infections (ODRIs) are a major source of concern to governments and healthcare institutes around the world. They cause significant impairment to patient health and often lead to implant failure and surgical interventions. Although, Gram-positive Staphylococcus species are the primary causes of ODRIs, Gram-negative bacteria such as E.coli can also cause these infections. The traditional strategies to combat ODRIs have relied heavily on antibiotics, which are becoming ineffectual due to the increasing prevalence of antibiotic-resistant bacteria. There is an urgent need to explore alternative antimicrobial agents and develop strategies for utilising them to combat ODRIs.
Antimicrobial peptides (AMPs) and their mimics have emerged as exciting alternatives to traditional antibiotics due to their broad-spectrum activity and the difficulty bacteria have in becoming resistant to them. AMPs are usually cationic, amphiphilic molecules that kill bacteria by disrupting their cell membranes. Mimics of AMPs are designed to replicate AMPs’ antibacterial properties but with improved pharmacological and therapeutic properties.
Our research is exploring the activity of AMPs and AMP mimics (peptidomimetics and polymers) as antibacterial coatings for hydroxyapatite (HA) surfaces. HA is a calcium phosphate ceramic used widely in orthopaedic biomaterials research due to its biocompatibility and compositional similarity with the inorganic phase of bone. Four different antibacterial entities, two AMPs, one small molecule peptidomimetic, and a polymer-based AMP mimic, have been successfully coated onto these materials via physical and covalent attachment techniques. For covalent attachment, plasma immersion ion implantation and deposition (PIIID) was utilised. All the coated HA surfaces have exhibited significant antibacterial activity with at least two-log reduction in viability of both Gram-positive and Gram-negative bacteria compared to uncoated control surfaces. The viability of human foetal osteoblast cells on the physically coated surfaces was reduced by 5-40% compared to uncoated controls.