Microenvironment of Bone and Joint Infection: Examining the Microenvironment

Periprosthetic joint infection (PJI) is a major complication of arthroplasty, and conventional diagnostic methods for PJI remain limited by suboptimal sensitivity, long turnaround times, high cost, and patient inconvenience, particularly in biofilm-associated and culture-negative infections. Emerging data suggest that the infected joint microenvironment contains host- and pathogen-derived molecular signatures with substantial diagnostic potential. This review evaluates current evidence on microenvironment-related biomarkers in PJI, including host extracellular vesicles, host cell-free nucleic acids (microRNA/cell-free DNA), non-host-derived biomarkers, and sequencing-based pathogen detection techniques. Host-derived biomarkers show favorable discriminatory capability by characterizing inflammatory and immune responses, and metagenomic and sequencing-based technologies improve pathogen identification. Despite encouraging diagnostic performance, widespread clinical implementation remains limited due to a lack of standardization, cost, and limited prospective validation. Future prospective multicenter studies should integrate conventional microbiological methods with molecular and microenvironment-based approaches to improve diagnostic accuracy.