Effects of intra-articular D-amino acids combined with systemic vancomycin on an experimental Staphylococcus aureus-induced periprosthetic joint infection

The D-isoforms of amino acids (D-AAs) exhibit anti-biofilm potential against a diverse range of bacterial species in vitro, while its role in vivo remains unclear. The aim of this study was to investigate the effects of a combination of D-AAs and vancomycin on a PJI rat model. Eight-week-old male SD rats were randomized to the control group, sham group, vancomycin group, D-AAs–vancomycin group. After treatment for 6 weeks, we analysed the levels of inflammatory factors in serum, behavioural change, imaging manifestations. The anti-biofilm ability of D-AAs was detected by crystal violet staining and scanning electron microscope observation, and its ability to assist antibiotics in killing bacteria was assessed by culture of bacteria. Additionally, micro-CT and histological analysis were used to evaluate the impact of D-AAs combined with vancomycin on the bone remodelling around the prosthesis. The group treated with a D-AAs–vancomycin combination sustained normal weight gain and exhibited reduced the serum levels of α2M, IL-1β, IL-6, IL-10, TNF-α and PGE2. Moreover, treated with D-AAs in combination with vancomycin improved the weight-bearing activity performance, increased the sizes and widths of distal femurs, and improved Rissing scale scoring. In particular, treatment using D-AAs enhanced the ability of vancomycin to eradicate Staphylococcus aureus, as demonstrated by the dispersion of existing biofilms and the inhibition of biofilm formation that occurred in a concentration-dependent manner. This treatment combination also resulted in a reduction in bacterial burden with in the soft tissues, bones, and implants. Furthermore, D-AAs–vancomycin combination treatment attenuated abnormal bone remodelling around the implant, as evidenced by an observed increase in BMD, BV/TV, and Tb.Th and the presence of reduced Trap+ osteoclasts and elevated osterix+ osteo-progenitors. Combining D-AAs with vancomycin provides an effective therapeutic strategy for the treatment of PJI by promoting biofilm dispersion to enhance antimicrobial activity.