Advances and Future Perspectives on Chitosan-Based Hydrogels for Bone Regeneration in Periodontitis-Associated Defects

Periodontitis-triggered alveolar bone loss is an irreversible pathological lesion that remains challenging to regenerate in clinical practice. Functionally modified chitosan (CS) hydrogels combine favorable biocompatibility, tunable biodegradability, intrinsic antibacterial activity, and immunomodulatory properties, rendering them promising scaffolds for the repair of inflammatory bone defects. This review summarizes advances over the past five years in the development of functionalized CS hydrogels for periodontitis-associated alveolar bone regeneration. We categorize and compare four mainstream modification strategies for CS: biomimetic structural design, inflammatory immunoregulation, stimuli-responsive controlled release, and mechanical microenvironment adaptation. Beyond hydrogels, chemically modified CS in diverse forms (membranes, bulk scaffolds, micro/nanoparticles, and surface coatings) is also discussed. Furthermore, we comprehensively elaborate on the core regenerative mechanisms of modified CS hydrogels, including antibacterial defense, immune microenvironment remodeling, osteogenic activation, and angiogenesis–osteogenesis coupling. Unlike most previous reviews covering CS biomaterials, the present work specifically focuses on the challenges of bone regeneration under periodontitis-related inflammatory conditions, with a small set of other bone regeneration studies included as supporting references. It examines the key limitations of current investigations—particularly those concerning mechanical matching, sustained anti-inflammatory efficacy, and clinical translatability—and outlines targeted research directions involving structural optimization, multistage cascade regulation, and personalized clinical translation. Overall, this review provides a theoretical framework and practical design strategies for developing high-performance CS-based hydrogels toward periodontal bone defect regeneration.