In-situ Gel Systems for Periodontitis: Advances in Localized Drug Delivery and Regenerative Therapy

Periodontitis is a chronic inflammatory condition initiated by pathogenic microbial biofilms and exacerbated by host immune responses, leading to progressive connective tissue and alveolar bone destruction and eventual tooth loss. Conventional therapies such as scaling and root planning, systemic antibiotics, and surgical interventions provide only short-term relief due to rapid drug clearance, limited penetration into deep periodontal pockets, and poor efficacy against structured biofilms. These limitations underscore the need for localized, sustained drug delivery systems capable of maintaining therapeutic concentrations at the target site. In-situ gel systems have emerged as innovative localized delivery platforms for periodontal therapy. Administered as liquids, they undergo sol-to-gel transitions in response to physiological stimuli such as temperature, pH, or ionic strength within the periodontal pocket, ensuring prolonged retention and improved therapeutic performance. Advances in polymer design, crosslinking chemistry, and fabrication methods including click reactions and supramolecular assembly have enhanced gel stability, responsiveness, and controlled release behaviour. Integration of nanotechnology, advanced biomaterials, three-dimensional bioprinting, and AI driven formulation strategies has further refined drug loading and delivery precision. Collectively, these innovations position smart in-situ gels as next generation systems for effective and sustained management of chronic periodontitis.