Development of an antimicrobial lipid coating to prevent infections in uncemented joint replacements

Preventing infections in joint replacements is a major ongoing challenge, with limited effective clinical technologies currently available for uncemented knee and hip prostheses. This research aims to develop a coating for titanium implants, consisting of a supported lipid bilayer (SLB) encapsulating an antimicrobial agent. The SLB will be robustly tethered to the titanium using self-assembled monolayers (SAMs) of octadecylphosphonic acid (ODPA). The chosen antimicrobial is Novobiocin, a coumarin-derived antibiotic known to be effective against resistant strains of Staphylococcus aureus.ODPA SAMs were deposited on TiO2-coated quartz crystal microbalance (QCM) sensors using two environmentally friendly non-polar solvents (anisole and cyclopentyl methyl ether, CPME), two concentrations of ODPA (0.5mM and 1mM) and two processing temperatures (21°C and 60°C). QCM, water contact angle measurements, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and temperature-programmed desorption mass spectrometry (TPD-MS) were used to characterise the ODPA SAM. A SLB with encapsulated Novobiocin was subsequently developed on the surface of the ODPA SAM using fluorescent lipids and a solvent assisted method. The prototype implant surface was tested for antimicrobial activity against S. aureus.A well-ordered, uniform ODPA SAM was rapidly formed using 0.5 mM ODPA in CPME at 21°C during 10 min, as confirmed by high Sauerbrey mass (≍285-290 ng/cm2), high atomic percentage phosphorus (detected using XPS) and high water contact angles (117.6±2.5°). QCM measurements combined with fluorescence microscopy provided evidence of complete planar lipid bilayer formation on the titanium surface using a solvent assisted method. Incorporation of Novobiocin into the SLB resulted in reduced attachment and viability of S. aureus.Key parameters were established for the rapid, robust and uniform formation of an ODPA SAM on titanium (solvent, temperature and concentration). This allowed the successful formation of an antimicrobial SLB, which demonstrated potential for reducing attachment and viability of pathogens associated with joint replacement infections