In vivo evaluation of the antibacterial properties of a poly-ε-lysine and hyaluronic acid coated intramedullary implant in a New Zealand White rabbit model

Peri-prosthetic joint infection (PJI) is a severe complication that can arise following joint replacement surgery. PJI treatment is extremely complex due to the formation of bacterial biofilms and the emergence of antimicrobial resistance (AMR) to antibiotic classes commonly used in the treatment of PJI. This critical development highlights the urgent need for novel prophylactic strategies that do not rely on conventional antibiotic agents to prevent bacterial adherence and subsequent biofilm formation on implant surfaces. This study evaluated the contact-killing properties of a supramolecular poly-epsilon-lysine and hyaluronic acid (PEL-10/HA-1) coating on an intramedullary nail in a New Zealand White (NZW) rabbit model. Fifteen female NZW rabbits were inoculated with Staphylococcus aureus (JAR 060131, 5.9 x 104 CFU in 100 µL PBS) in the right humerus. Seven received an uncoated nail, while eight received a PEL-10/HA-1 coated titanium alloy nail. After 7 days, the rabbits were euthanized for microbiological analysis of the nail and surrounding tissues. Remarkably, microbiological analysis showed that 4/8 of the rabbits with a coated nail had 0 CFU on the nail, versus 1/8 of the rabbits with an uncoated nail. The rinsing solution, soft tissue, and bone samples from the rabbits with a coated nail were more often culture-negative than the samples from rabbits with an uncoated nail. However, no statistically significant differences were observed between the CFUs of the coated and uncoated groups. There were no statistically significant differences between the coated and uncoated groups in other infection indicators, including white blood cell count, C-reactive protein, and plasma protein electrophoresis. While the PEL-10/HA-1 coating had a bacteriostatic and bactericidal effect in vitro, this effect did not translate to in vivo, highlighting a translational gap. The PEL-10/HA-1 coating must be optimized to enhance its antimicrobial effect, ensuring the same promising in vivo effect as previously observed in vitro.