KL‐12 Peptide Targets Peri‐Implantitis via Dual Antibacterial and Immunomodulatory Effects

AIMS: Peri-implantitis is a common dental complication characterized by inflammation of peri-implant tissues and progressive bone loss. With the rise of antibiotic resistance, this study investigates the potential of antimicrobial peptides (AMPs), specifically KL-12, a novel peptide derived from cecropin B, as an alternative therapeutic strategy against Porphyromonas gingivalis, a key pathogen in peri-implantitis. METHODS: We evaluated the structural stability, antibacterial efficacy, and cytotoxicity of KL-12. Antibacterial activity was measured against P. gingivalis, while the peptide's mode of action was explored concerning its effect on the gingipain proteases essential for the bacterium's nutrient acquisition. Additionally, we assessed KL-12's impact on macrophage polarization and anti-inflammatory responses. RESULTS: The findings revealed that KL-12 exhibited significant antibacterial activity against P. gingivalis and demonstrated potential as a specific inhibitor of gingipains. It was observed that KL-12 disrupts bacterial viability through mechanisms involving deformation and nutrient deprivation, rather than traditional pore formation. KL-12 effectively modulated macrophage polarization, promoting M2 differentiation and enhancing anti-inflammatory responses. CONCLUSION: These results suggest that KL-12 functions as a dual-action therapeutic agent, targeting both bacterial pathogens and inflammatory processes in the management of peri-implantitis. Future studies will aim to clarify the molecular mechanisms underlying KL-12's antibacterial and immunomodulatory effects.