Bioactive Peptides for Oral Diseases: Biomaterial-Assisted Therapeutics and Translational Applications.

Dental caries, periodontitis, oral mucosal inflammation, peri-implant infections, and oral tissue defects remain major clinical burdens. Conventional treatments, including antimicrobials, antibiotics, anti-inflammatory agents, and regenerative materials, are frequently limited by rapid clearance from saliva-exposed oral surfaces, insufficient discrimination between pathogenic and commensal microorganisms or between diseased and healthy tissues, antimicrobial resistance in biofilm-associated infections, and inadequate support for functional tissue repair. In this context, bioactive peptides have emerged as promising therapeutic agents for oral applications because of their structural tunability, biocompatibility, and broad antimicrobial, antibiofilm, immunomodulatory, and regenerative activities. However, their clinical translation is restricted by enzymatic instability, short residence time, limited penetration in complex oral microenvironments, and inefficient delivery. This review summarizes recent progress in bioactive peptides for oral diseases, with particular emphasis on biomaterial-assisted therapeutic strategies. We discuss how peptide design, functional modification, and biomaterial platforms, including nanoparticles, hydrogels, coatings, and mucoadhesive systems, improve peptide stability, local retention, controlled release, and site-specific activity. We further highlight applications in infection control, inflammation regulation, soft and hard tissue regeneration, biosensing, and targeted therapy. Finally, we outline translational challenges, including safety evaluation, scalable manufacturing, and reproducibility, and discuss emerging solutions enabled by rational peptide engineering, artificial intelligence-guided design, and synthetic biology. Overall, integrating bioactive peptides with applied biomaterial systems provides a promising framework for next-generation oral therapeutics.