Hyaluronic Acid and Sodium Hypochlorite as Adjunctive Therapeutic Options for Patients with Periodontal Disease: A Systematic Review

<b>Background:</b> Periodontal disease is a chronic multifactorial inflammatory condition caused by dysbiosis of the dental biofilm, leading to destruction of the connective tissue attachment, alveolar bone resorption, and potentially tooth loss. Non-surgical periodontal therapy (NSPT), involving subgingival instrumentation, aims to restore periodontal health by reducing the probing pocket depth (PPD) and bleeding on probing (BOP) and by improving the clinical attachment level (CAL). The adjunctive use of chemical agents, such as sodium hypochlorite/amino acids (NaOCl) and cross-linked hyaluronic acid (xHyA) gels, has been proposed to enhance the efficacy of NSPT. <b>Objective:</b> This systematic review aimed to evaluate the clinical effectiveness of the subgingival application of NaOCl and xHyA gels as adjunctive therapies to NSPT in patients with periodontal disease. <b>Materials and Methods:</b> A comprehensive literature search was conducted in the MEDLINE (PubMed), Cochrane Library, Web of Science, and Scopus databases following PRISMA guidelines. The review was registered in PROSPERO (CRD420251074045). Randomized clinical trials (RCTs) in human subjects with a follow-up of at least 6 months were included if they assessed outcomes such as PPD, CAL, BOP, or radiographic bone loss (RBL). Studies involving the adjunctive use of NaOCl and xHyA gels were selected according to the PICOS strategy. <b>Results:</b> Two RCTs published between 2023 and 2024, with follow-ups ranging from 6 to 9 months and involving 48-50 patients, met the inclusion criteria. Both studies demonstrated significant improvements in clinical outcomes when sodium hypochlorite and hyaluronic acid were used adjunctively with NSPT compared to when NSPT was used alone. Sites treated with adjunctive therapy showed significantly greater reductions in PPD and greater CAL gains over time. Pocket closure rates were also markedly higher in deep sites (>7 mm) in the adjunctive group than in the control group, indicating a substantial regenerative potential and a possible reduction in the need for surgical intervention. Gingival recession exhibited more favorable recovery trends in the adjunctive group, while BOP frequency decreased in both groups without statistically significant differences. <b>Conclusions:</b> The adjunctive use of NaOCl and xHyA gels in non-surgical periodontal therapy significantly enhances clinical outcomes compared with the use of mechanical debridement alone.