Hyaluronic Acid and β-Tricalcium Phosphate in Periodontal Pocket Therapy and Alveolar Bone Augmentation: A Systematic Review

Background: Hyaluronic acid (HA) and β-tricalcium phosphate (β-TCP) are widely used biomaterials in periodontal and alveolar regeneration; however, their complementary biological roles across soft- and hard-tissue healing have not been jointly assessed in a single review. Objective: to systematically evaluate clinical and translational evidence regarding the adjunctive use of HA in periodontal therapy and the regenerative performance of β-TCP in alveolar bone reconstruction. Methods: A systematic search was conducted across PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Embase for studies published between 1 January 2015 and 1 October 2025. Randomized and non-randomized clinical studies evaluating HA as an adjunct to periodontal therapy and β-TCP in ridge preservation or augmentation were included. In vitro studies were considered when providing mechanistic insight relevant to clinical outcomes. Screening, data extraction, and qualitative synthesis were performed according to PRISMA 2020 guidelines. Results: Database searching identified 312 records. After removal of duplicates, 241 records were screened, of which 179 were excluded. Sixty-two full-text articles were assessed for eligibility, and twenty studies met the inclusion criteria (twelve clinical; eight in vitro). Across non-surgical periodontal therapy trials, adjunctive HA demonstrated modest but consistent additional improvements in probing depth reduction (~0.8–1.5 mm) and clinical attachment gain (~0.5–1.2 mm) compared with mechanical therapy alone, particularly in deeper defects and systemically compromised patients. Clinical studies on β-TCP reported predictable dimensional bone preservation and stable implant feasibility, supported by histologic evidence of scaffold-guided new bone formation. In vitro findings indicated that HA modulates biofilm-induced inflammation and supports fibroblast and epithelial cell function, whereas β-TCP promotes osteoblast activity and controlled osteoclast-mediated remodeling. Conclusions: HA and β-TCP demonstrate complementary regenerative roles, with HA primarily enhancing soft-tissue resolution and inflammatory modulation and β-TCP providing osteoconductive structural support for bone regeneration. Current evidence supports their selective integration in personalized regenerative approaches; however, standardized outcome reporting and longer-term trials are required to establish the clinical value of sequential or combined application.