HISTOLOGICAL TIMELINE DEFINING ACUTE AND CHRONIC PERIPROSTHETIC JOINT INFECTION IN A MOUSE ARTHROPLASTY MODEL

Aim Periprosthetic joint infection (PJI) complicates 2% of primary arthroplasties, constitutes 25% of revisions, and incurs an annual U.S. healthcare cost of $1.6 billion 1 . Accurate staging is critical as DAIR success rates drop from 74% within 30 days to 44% once chronic infection occurs 2 . Currently, staging relies heavily on symptom duration rather than objective tissue-based criteria. The 2018 International Consensus Meeting highlighted the need for objective markers distinguishing acute from chronic PJI 3 . Existing animal studies have inadequately defined intermediate inflammatory transitions 4,5 . Our study aimed to characterize inflammatory progression and identify clear histological markers of the acute-to-chronic transition using our load-bearing tibial implant mouse model 6 . Method Twenty 12-week-old C57BL/6 mice underwent unilateral proximal tibial implantation and inoculation with 3×10⁴ CFUs of bioluminescent Staphylococcus aureus. Animals were euthanized at 48 hours and days 7, 10, 14, 18, 21, and 28 postoperatively. Radiographs and serum inflammatory markers were assessed. Fixed limb cryosections were stained (haematoxylin-eosin) and semi-quantitatively graded (0–3) for neutrophils, macrophages/lymphocytes, edema/fibrin, and bone necrosis (Figure 1A-B) . Acute PJI was defined by neutrophil score ≥2 and macrophage/lymphocyte score ≤1; chronic PJI required macrophage/lymphocyte score ≥2 with fibrosis or bone necrosis score ≥1. All slides were independently reviewed and scored by a US board‑certified pathologist. Results Peak neutrophil infiltration and edema/fibrin deposition (grade 3) occurred on day 7, coinciding with microabscess formation (1C). By day 14, acute inflammation significantly declined (grades 0–1), while macrophage/lymphocyte infiltration and fibrosis markedly increased (grades 2–3). Bone necrosis appeared after day 18 (1D) . Conclusions Neutrophil-driven acute inflammation peaked by day 7, shifting to macrophage-rich inflammation by day 14. This transition parallels the inflammatory shift described in human periprosthetic membranes 7 . Thus, the period between postoperative days 7-14 represents a critical acute-to-chronic transition window in this load-bearing mouse model of PJI. For any figures or tables, please contact the authors directly.