Periprosthetic Joint Infection: Biofilm Pathogenesis, Immune Dysregulation, and Emerging Prosthetic Interface Strategies

Periprosthetic joint infection (PJI) remains a major clinical challenge after total joint arthroplasty because of its association with prolonged antimicrobial therapy, repeated surgery, implant failure, functional disability, and substantial socioeconomic burden. Current strategies, including systemic antibiotics, debridement with implant retention, staged revision, and antibiotic-loaded cement spacers, remain indispensable but are limited by mature biofilm tolerance, protected microbial reservoirs, insufficient local drug penetration, persistent inflammation, and compromised periprosthetic bone repair. Increasing evidence indicates that PJI is not merely bacterial colonization of an implant surface, but a dynamic prosthetic interface disorder involving biofilm persistence, immune dysregulation, inflammatory osteolysis, and failed osseointegration. This review summarizes recent advances in anti-infective prosthetic interface design, emphasizing the transition from passive antibacterial coatings toward multifunctional immuno-antibacterial osseointegrative systems. The pathogenic basis of PJI is first discussed, including conditioning film formation, bacterial adhesion, biofilm maturation, protected reservoirs, immune evasion, and osteolysis. Current clinical management limitations are then evaluated, followed by emerging biomaterial strategies, including anti-adhesive and contact-killing surfaces, active antimicrobial coatings, mature biofilm disruption, biological antibiofilm therapies, smart infection-responsive delivery systems, and osteoimmunomodulatory interfaces. Particular attention is given to balancing early antibacterial activity with cytocompatibility, immune resolution, angiogenesis, mechanical durability, and long-term osseointegration. Finally, key translational barriers are highlighted, including load-bearing and tribological constraints, insufficiently standardized mature biofilm and animal models, limited clinical evidence for advanced smart materials, manufacturing reproducibility, sterilization compatibility, regulatory complexity, and application-specific clinical readiness. Future anti-PJI interfaces should evolve beyond unidirectional bacterial killing toward stage-specific systems integrating biofilm control, immune restoration, vascularized bone regeneration, and durable mechanical performance.