Abstract
Periodontitis is a chronic inflammatory oral disease characterized by irreversible alveolar bone resorption, which severely impairs oral health and even leads to tooth loss. Clinical bone augmentation therapy for alveolar bone defects mainly relies on exogenous bone substitute materials. However, traditional materials are prone to implantation failure due to the persistent inflammatory microenvironment and bacterial infection in the periodontal area. The addition of antibiotics to improve antibacterial properties not only induces bacterial resistance but also causes systemic toxic and side effects, making it difficult to meet clinical treatment needs. This review focuses on the core demand for bone substitute materials in periodontitis treatment to simultaneously achieve antibacterial, anti-inflammatory, and osteogenic functions—an essential characteristic that distinguishes such materials from conventional antibacterial drugs and single-function bone graft materials. We systematically elaborate on multiple interrelated inflammatory signaling pathways (e.g., RANKL/RANK/OPG, cGAS-STING, NF-κB, JAK-STAT, MAPK, PI3K/AKT, HIF-1, TGF-β/SMAD, Wnt/β-catenin, Hippo) and inflammasome mechanisms involved in periodontitis-associated alveolar bone resorption, exploring potential targets for screening excellent anti-inflammatory and osteogenic active molecules. On this basis, we summarize modification strategies for bioceramic bone tissue-engineered substitutes, including incorporating metal ions (Ag, Cu, Sr, Mn, Mg, Zn, etc.) and natural anti-inflammatory molecules into the material matrix to enhance their multifunctional properties while maintaining favorable physical and biological characteristics. We also discuss structural and functional optimization of composites via surface morphology modification, photothermal, and photodynamic coating construction to improve adaptability to the periodontal inflammatory microenvironment. These reconstructed multifunctional composite bioceramic materials integrate antibacterial, anti-inflammatory, and osteogenic functions, eliminating periodontal bacterial infection, alleviating local chronic inflammation, and actively promoting osteoblast differentiation and alveolar bone defect repair, thereby perfectly matching the pathological characteristics of periodontitis. This review clarifies the core design concept of multifunctional integration for bioceramic bone tissue-engineered substitutes in periodontitis treatment and provides a theoretical basis and technical reference for developing novel bone graft materials with clinical transformation potential.