Reimagining periodontal regeneration: smart biomaterials for a complex tissue landscape

Periodontitis is a prevalent chronic inflammatory disease and a major cause of tooth loss and systemic complications. Due to its progressive, often asymptomatic nature, substantial destruction of the cementum, periodontal ligament and alveolar bone is frequently present at the time of diagnosis, highlighting the urgent need for functional periodontal regeneration. Conventional biomaterials primarily serve as passive scaffolds and rarely enable the coordinated regeneration of multiple periodontal tissues. Recently, smart biomaterials have emerged as a promising strategy to address these limitations. By integrating stimulus responsiveness, bio-instructive and immunomodulatory functions and spatiotemporal control of therapeutic cues, these materials could dynamically interact with the diseased microenvironment to enhance regenerative outcomes for future periodontal therapy. In this review, we summarize the key biological and mechanistic barriers to periodontal regeneration, including multi-tissue coordination, microbial challenges, dysregulated inflammation and mechanical loading. We discuss how smart biomaterials are designed to overcome these obstacles through microenvironment-responsive delivery, immune modulation and interface-oriented regeneration. Finally, we highlight key design principles, evaluation frameworks and the translational relevance of animal models for periodontal biomaterials development. Smart biomaterials represent a transition from passive scaffolds to dynamic, immuno-instructive systems for periodontal regeneration.