Advances in Necrotizing Fasciitis Animal Models: Current Trends and Future Perspectives.

Necrotizing fasciitis (NF) is a rapidly progressive soft tissue infection with high morbidity and mortality, yet its pathophysiology remains incompletely understood. Animal models are indispensable for dissecting disease mechanisms and testing therapeutic interventions, yet their translational relevance varies across species and experimental approaches. This review critically evaluates NF models in rodents, zebrafish, rabbits, pigs, and non-human primates, highlighting their relative strengths in replicating immunopathology, systemic dissemination, and biofilm-driven persistence. We examine methodological strategies including bacterial inoculation, trauma-induced infection, immunosuppression-enhanced infection, genetic engineering, and optical imaging, and discuss how these frameworks capture discrete aspects of NF pathogenesis. Emerging technologies, including CRISPR-mediated host factor engineering, multi-omics profiling, intravital and high-resolution imaging, organ-on-chip platforms, and artificial intelligence, are integrated into next-generation models to enhance predictive power, mechanistic insight, and translational fidelity. We also outline innovative therapeutic strategies validated in preclinical models, from precision-targeted monoclonal antibodies and immunotherapies to advanced drug delivery systems and AI-guided predictive modeling. Finally, we discuss practical and ethical considerations for NF modeling, emphasizing reproducibility, standardization, and the 3Rs principle, and propose a forward-looking framework for integrating in vivo, in vitro, and in silico platforms. Collectively, these insights provide a roadmap for refining NF animal models, accelerating mechanistic discovery, and informing clinically relevant interventions.