Recent Advances in Natural Polymers-based Hydrogels for Periodontal Regeneration.

Abstract

Conventional therapies still provide only limited true tissue regeneration for periodontal diseases, particularly periodontitis, which are highly prevalent chronic inflammatory conditions associated with irreversible loss of tooth-supporting tissues and relevant systemic consequences. In this context, hydrogels based on natural polymers have been widely explored in periodontal tissue engineering as biomimetic matrices capable of modulating the inflammatory response, enabling localized delivery of bioactive agents, and offering temporary structural support. This review summarizes recent advances in hydrogels composed of alginate, collagen, chitosan, and other natural or semi-synthetic polymers applied to periodontal regeneration. The influence of polymer origin, crosslinking strategies, physicochemical and rheological properties, and processing approaches, including injectable formulations, self-healing systems, and bioinks for three-dimensional bioprinting, is discussed in relation to cell adhesion, angiogenesis, osteogenesis, and functional restoration of periodontal tissues. Hybrid platforms such as interpenetrating polymer networks, ceramic-reinforced composites, and systems designed for controlled delivery of drugs, growth factors, exosomes, and stem cells are also examined, with emphasis on immunomodulatory and stimuli-responsive designs tailored to the periodontal microenvironment. Despite robust preclinical evidence demonstrating coordinated regeneration of cementum, periodontal ligament, and alveolar bone, major challenges remain. These include the scarcity of well-controlled clinical trials, limitations in standardization, and regulatory barriers to translation.