Periodontal tissue regeneration remains a major challenge in oral regenerative medicine, aiming to restore functional structures such as cementum, periodontal ligament, and alveolar bone. Animal models are essential for evaluating the biocompatibility and regenerative efficacy of biomaterials, elucidating repair mechanisms, and supporting clinical translation. This review systematically summarizes chronic and acute periodontal defect models, their establishment protocols, and applications, covering oral gavage, periodontal inoculation, ligature, fenestration, dehiscence, intrabony, and furcation defects. The advantages and limitations of each model are analyzed in relation to simulating pathological microenvironments, testing regenerative scaffolds, and assessing drug delivery systems, with attention to combined modeling strategies. Evaluation methods from histology and immunohistochemistry to molecular assays and omics technologies are outlined, forming a multilevel assessment framework. Integrative multiomics approaches reveal key signaling pathways and metabolic networks in regeneration, guiding biomaterial design and targeted therapy development. This review offers a comprehensive methodological reference to bridge basic research with clinical application and to optimize experimental systems.
Impact Statement
In this review, we provide a comprehensive summary of chronic and acute animal models for periodontal regeneration and their application in evaluating biomaterial-based therapeutic strategies. We discuss model selection principles, surgical protocols, and the simulation of pathological microenvironments, along with integrated histological, immunohistochemical, molecular, and multiomics evaluation methods. By highlighting each model’s strengths and limitations, this review offers methodological guidance to improve reproducibility, elucidate regenerative mechanisms, and inform the rational design of biomaterials for periodontal tissue engineering, thereby strengthening the experimental foundation for future clinical translation.
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