Background <p>Joint arthroplasty, replacement of damaged articular surfaces with a prosthetic component, is an increasingly common orthopaedic procedure. Despite the overall success of arthroplasty, complications such as periprosthetic joint infection remain a persistent problem with severe consequences. With increasing clinical demands, the need for a reliable, reproducible model for testing therapeutic strategies for arthroplasty complications is fundamental.</p> Results <p>In this study, a novel small animal model was designed and evaluated for downstream investigations. Two different implant designs (tibial vs. femoral) and surgical approaches were compared. The femoral implant resulted in fewer complications such as knee joint destabilization, severe swelling, and erosion of articular cartilage and subchondral bone. Rabbit care methodology was also optimized during model development, and both the process and results are presented to promote ethical and reproducible preclinical model research.</p> Conclusions <p>The custom porous coated unicondylar femoral implant with a polished condylar surface demonstrated far fewer complications and adverse events than the tibial implant, as well as robust osseointegration. This will serve as a model for future investigations in preventing and treating joint arthroplasty complications.</p>