Bioactive Peptides with Biomaterials Offer Next-Generation Therapeutics for Oral Diseases

Dental caries, periodontitis, oral mucosal inflammation, and peri-implant infections represent significant clinical burdens. Current treatments, including antimicrobials and regenerative materials, often fail due to rapid clearance, poor pathogen discrimination, antimicrobial resistance in biofilms, and inadequate tissue repair support. Bioactive peptides offer a compelling alternative, possessing inherent antimicrobial, antibiofilm, immunomodulatory, and regenerative properties. However, their clinical utility is hampered by enzymatic instability, short residence times in the oral cavity, and limited penetration, necessitating advanced delivery strategies.

This comprehensive review synthesizes recent progress in bioactive peptides for oral applications, specifically emphasizing biomaterial-assisted therapeutic strategies. The authors discuss how rational peptide design, functional modification, and integration with various biomaterial platforms, including nanoparticles, hydrogels, coatings, and mucoadhesive systems, address key limitations. The review highlights applications across infection control, inflammation regulation, soft and hard tissue regeneration, biosensing, and targeted therapy, while also outlining critical translational challenges and emerging solutions.

The review identifies that integrating bioactive peptides with biomaterials significantly improves their therapeutic profile by enhancing stability, local retention, controlled release, and site-specific activity. These advanced systems enable more effective infection control by disrupting biofilms and combating antimicrobial resistance, and better inflammation regulation through immunomodulatory actions. Furthermore, biomaterial-peptide composites actively support both soft and hard oral tissue regeneration, addressing defects that conventional methods struggle with. The authors detail how peptide engineering, artificial intelligence-guided design, and synthetic biology are providing solutions to current translational hurdles such as safety evaluation, scalable manufacturing, and reproducibility. > Biomaterial platforms effectively overcome the inherent enzymatic instability and short residence time of bioactive peptides, unlocking their full therapeutic potential for complex oral microenvironments.