Antimicrobial peptides are emerging as a significant advancement in oral medicine, offering potential solutions for diseases affecting approximately 3.5 billion people globally. Traditional treatments relying on antibiotics face diminishing effectiveness due to widespread bacterial resistance, creating an urgent need for safe and effective alternatives.
Unlike conventional antibiotics that target specific metabolic pathways, antimicrobial peptides primarily act by physically destroying microbial cell membranes. This unique mechanism minimizes the risk of inducing resistance while providing broad-spectrum antimicrobial activity. These small-molecule polypeptides, key components of the innate immune system, also possess multiple biological functions including immunomodulation, inflammation reduction, and tissue regeneration promotion.
Research published in Translational Dental Research comprehensively reviews AMP classification, antimicrobial mechanisms, and therapeutic applications in major oral diseases. For dental caries, peptides like Temporin-GHa derivatives, ZXR-2, and GH12 inhibit cariogenic bacteria such as Streptococcus mutans, interfere with biofilm formation, and promote tooth remineralization.
In periodontitis treatment, human-derived AMPs including α-defensins and β-defensins, along with synthetic peptides like Nal-P-113, effectively kill periodontal pathogens while regulating inflammatory responses and enhancing tissue regeneration. For oral cancer therapy, peptides such as Piscidin-1 and LL-37 induce cancer cell death through membrane disruption and apoptotic pathways while modulating anti-tumor immune responses.
Several AMPs have progressed to clinical trials, demonstrating their practical potential. C16G2 is being tested for dental caries, Nal-P-113 for periodontitis, and P-113 for oral candidiasis. Beyond direct therapeutic applications, AMPs are being developed into implant coatings to prevent peri-implant infections, incorporated into oral dressings for sustained release, and combined with antibiotics or nanoparticles to enhance therapeutic effects. They also show promise as diagnostic markers for oral diseases through detection of expression level changes.
Despite this potential, clinical translation faces significant challenges. Oral enzymes, pH fluctuations, and high salt concentrations affect peptide stability, while cationic and amphiphilic properties may lead to cytotoxicity and immunogenicity concerns. Large-scale production also presents cost challenges that must be addressed for widespread clinical adoption.
Researchers have developed multiple strategies to overcome these obstacles, including chemical modification through N-acetylation and lipidation, nanocarrier delivery systems, sequence optimization with D-amino acids, and microbial or plant-based heterologous expression systems. These approaches aim to improve stability, reduce toxicity, and lower production costs while maintaining therapeutic efficacy.
The multifunctional properties and low resistance potential of antimicrobial peptides position them as transformative agents in oral medicine. Future research directions include clarifying interaction mechanisms with oral microbiota and host cells, accelerating peptide screening through artificial intelligence, and developing formulations specifically tailored for the unique oral microenvironment. As antibiotic resistance continues to threaten global health, these peptides offer a promising pathway toward more sustainable and effective oral disease management.
