Current and emerging antibacterial strategies for periprosthetic joint infection: An overview

Periprosthetic Joint Infection (PJI) represents one of the most serious complications following joint arthroplasty, with impactful consequences in the clinic and economy. Characterized by biofilm formation on implant surfaces, PJI poses significant therapeutic challenges due to the limited efficacy of systemic antibiotics and the increasing prevalence of multidrug-resistant bacteria. This review paper presents a comprehensive analysis of current and emerging antibacterial strategies designed to mitigate the risk of infection in total joint arthroplasty (TJA). It spans two decades of literature, from 2003 to 2025, with a particular focus on local antibiotic delivery systems, including bone cements, spacers, beads, and novel biomaterial carriers evaluated across in vitro assays, in vivo animal models, and in vivo clinical trials. A systematic search of the Web of Science Core Collection (1 January 2003-31 December 2025; last search: October 2025) identified 300 records; after de-duplication and screening, 138 studies met inclusion criteria (14 in vitro, 25 animal, 99 clinical). Evidence was synthesized using a clinical-pathway framework comparing PMMA-based strategies with resorbable depots, hydrogels, coatings/nanomaterials, and emerging antibiofilm agents. The performance of PolyMethylMethAcrylate (PMMA)-based Antibiotic-Loaded Bone Cements (ALBCs) is critically assessed, highlighting key limitations such as inconsistent drug release, suboptimal biofilm penetration, and their inability to degrade within the living tissue environment and consequently to not promote osseointegration. In contrast, recent developments in multifunctional scaffolds, bioresorbable polymers, and nanocomposite materials are explored as promising solutions for controlled antibiotic release, improved biocompatibility, and enhanced osseointegration. In addition to analysing drug release kinetics and antibacterial efficacy, this review discusses cytotoxicity, nephrotoxicity, and the systemic impact of locally delivered antibiotics. Particular attention is paid to the balance between therapeutic effectiveness and host safety. Furthermore, strategies against biofilm formation, such as surface modification, antimicrobial peptides, and metal-based coatings, are examined. By organizing the findings into a structured comparative framework, this review provides valuable insight into the advantages, limitations, and translational potential of each approach. Finally, future perspectives are outlined, emphasizing the need for advanced clinical validation of next-generation biomaterials that can simultaneously address infection control and regenerative requirements in orthopaedic surgery.