Chitosan-Based Hydrogels for Periodontal Therapy: From Drug-Polymer Chemistry to Smart Multifunctional and Regenerative Systems

Periodontitis is a chronic, multifactorial inflammatory disease driven by microbial dysbiosis, oxidative stress, and dysregulated host immune responses, resulting in progressive destruction of periodontal tissues and, ultimately, tooth loss. Traditional treatments, including scaling and root planing and systemic antibiotics, have limitations due to incomplete bacterial elimination, poor site specificity, short drug retention, systemic side effects, and limited regenerative support. Recently, chitosan (CS)-based hydrogels have emerged as promising biomaterials for localized periodontal treatment owing to their biocompatibility, biodegradability, mucoadhesive nature, and ease of chemical modification. This review critically discusses recent developments in CS-based hydrogel systems functionalized with antibiotics, phytochemicals, anti-inflammatory agents, nanoparticles, regenerative molecules, and stimuli-responsive materials for the management of periodontitis. It primarily focuses on periodontal pathophysiology, therapeutic strategies, and drug-polymer interactions that affect its performance. Furthermore, it highlights emerging smart hydrogel systems that respond to pH, reactive oxygen species, temperature, and enzymatic activity within the periodontal microenvironment for controlled, targeted drug delivery. Future perspectives involve the development of multi-stimuli-responsive, microbiome-preserving, self-healing, and personalized hydrogel platforms capable of sequential drug delivery and periodontal regeneration. On the whole, this review bridges the gap between materials chemistry and clinical applicability, providing insights into design of next-generation CS-based hydrogels for targeted periodontal therapy.