Metformin is currently the first-line drug for the treatment of diabetes. In addition to its hypoglycemic effect, it has also been found to have other potential effects, such as anti-inflammatory, odontogenic differentiation-promoting, osteogenic differentiation-promoting, and antitumor effects. Previous studies have shown that metformin can promote the healing of periapical lesions, and its mechanism may be related to the promotion of osteogenic differentiation and the induction of dental pulp cell differentiation by activation of adenylate-activated protein kinase by dimethyldiphosphate. Clinical indexes, such as the probing depth, attachment loss level and probing bleeding index, were significantly improved in patients with periodontitis treated with metformin, which may play a role in the prevention and treatment of periodontal disease by promoting the proliferation, migration and osteogenic differentiation of periodontal ligament stem cells. Metformin has been proven to inhibit the growth and proliferation of tumor cells and plays an important role in the prevention and treatment of oral tumors such as oral squamous cell carcinoma. At present, research remains in the in vitro and animal experimental stage, and the related mechanism needs to be further explored. Clinical trials remain in the evaluation of clinical indicators, so large-scale, long-term, multicenter, randomized controlled clinical trials need to be further developed.

Glass ionomer cement (GIC) is widely used as a common filling material in dentistry but still exhibits problems with secondary caries and fractures. Thus, the antibacterial and anti-caries performance of GIC needs to be further improved. In recent years, natural antimicrobial components have become more desirable due to their good biological properties and low drug resistance. In this review, the natural antimicrobial ingredients in GIC modification are classified, reviewed and summarized according to the different sources of antimicrobial ingredients. In terms of animal origin, chitosan and casein phosphopeptide-amorphous calcium phosphate exhibit antimicrobial properties without affecting the mechanical properties of materials; propolis and bioactive enzymes have good biocompatibility; in terms of plant origin, polyphenols help improve the antimicrobial and mechanical properties of the material; arginine has a good remineralization effect; and plant essential oils have a certain ion release effect. In terms of microbial origin, antibiotics greatly improve the antibacterial properties of materials; in addition, the combined application of natural antimicrobial ingredients also exhibited excellent performance. Despite these advantages, the optimal addition concentration and biocompatibility in vivo are questions that need to be further explored before clinical applications can be achieved.

The efficacy of root canal therapy, as a core intervention for endodontic and periapical diseases, is highly dependent on the effectiveness of antimicrobial drugs. Although traditional drugs such as calcium hydroxide, chlorhexidine, and antibiotic pastes commonly used in the clinic play a role in preventing and controlling infections, they have obvious limitations. These drugs influence the mechanical properties of dentin, insufficiently solubilize necrotic tissues, and are susceptible to bacterial resistance, which makes achieving the desired effectiveness and safety difficult. Traditional macromolecular root canal drugs also face the challenge of the complexity of the root canal system. With the rapid development of material science in recent years, new antimicrobial agents have emerged. Metallic nanomaterials such as silver nanoparticles and zinc oxide nanoparticles are widely used in the medical field due to their unique physicochemical properties and superior antimicrobial properties. Chitosan nanoparticles have superior biosafety, calcium hydroxide nanoparticles compensate for the limitations of traditional calcium hydroxide formulations, and quaternary ammonium polyethyleneimine nanoparticles can confer antimicrobial properties to existing oral materials. Novel antimicrobial nanoparticles using nano-delivery systems, such as mesoporous calcium silicate and mesoporous silica, carry antimicrobial molecules with significant advantages in terms of anti-biofilm, biosafety, and promotion of tissue repair. Further, these agents reduce drug resistance, which improves prospects for application compared to traditional root canal disinfection drugs. The breakthrough of nanotechnology provides a novel direction for the innovation of root canal treatment drugs. Therefore, this paper reviews the research progress of nano-antimicrobial materials in root canal therapy.