Periodontitis is a chronic inflammatory disease that leads to the destruction of the supporting tissues of the teeth. Non-surgical periodontal treatment is the first-line approach for the management of periodontitis; however, the use of adjunctive therapeutic agents may improve clinical outcomes.

The aim of this randomized clinical trial is to evaluate the effects of hyaluronic acid gel and albumin platelet-rich fibrin (Alb-PRF) used as adjuncts to non-surgical periodontal treatment on clinical and biochemical parameters in patients with Stage III periodontitis. Participants will be randomly allocated into three groups: an Alb-PRF group, a hyaluronic acid gel group, and a control group receiving non-surgical periodontal treatment alone. Clinical periodontal parameters and biochemical markers obtained from gingival crevicular fluid will be assessed at baseline and at 1 and 3 months after treatment. The findings of this study are expected to contribute to the evaluation of the potential benefits of adjunctive biological and anti-inflammatory applications in the non-surgical periodontal treatment of patients with Stage III periodontitis.v

This study is designed as a randomized, parallel-group clinical trial conducted in patients diagnosed with Stage III periodontitis. The aim of the study is to evaluate the adjunctive effects of hyaluronic acid gel and albumin platelet-rich fibrin (Alb-PRF) when used in addition to non-surgical periodontal treatment.

A total of 51 systemically healthy volunteers will be included in the study. Participants will be randomly allocated into three groups (17 patient per group). At the initial visit, all participants will undergo clinical periodontal examination, intraoral photography, and gingival crevicular fluid sampling. Supragingival scaling will be performed for all patients at baseline. One week later, full-mouth scaling and root planing will be completed in a single session.

In the Alb-PRF group, albumin platelet-rich fibrin will be applied as an adjunctive therapy. In the hyaluronic acid group, hyaluronic acid gel will be applied following scaling and root planing and the application will be repeated at the second week. The control group will receive non-surgical periodontal treatment alone without any adjunctive application. Adjunctive treatments will be applied subgingivally immediately after periodontal therapy and one week later.

To evaluate clinical and biochemical outcomes, clinical periodontal parameters and gingival crevicular fluid samples will be collected at baseline and at 1 and 3 months after treatment. Gingival crevicular fluid samples will be obtained using sterile paper strips as a non-invasive method. All collected data will be evaluated at the end of the study. The results of this study are expected to provide additional evidence regarding the effectiveness of adjunctive biological and anti-inflammatory approaches in the non-surgical treatment of Stage III periodontitis.

Inclusion Criteria:

• Systemically healthy individuals aged between 30 and 60 years
• No history of periodontal treatment or antibiotic use within the last 6 months
• Non-smokers
• Accepting to regularly attend the follow-up sessions planned during the study period
• Diagnosis of Stage III periodontitis
• Presence of at least 15 teeth in the oral cavity, with more than 30% of the existing teeth affected by periodontal disease
• Presence of probing pocket depth ≥6 mm and clinical attachment loss ≥5 mm in affected teeth
• Presence of vertical bone loss ≥3 mm
• Radiographic evidence of alveolar bone loss extending to the middle third or beyond (≥33%) of the root length in affected teeth

Exclusion Criteria:

• Presence of any systemic disease
• History of periodontal treatment or antibiotic use within the last 6 months
• Pregnancy or lactation
• Presence of acute oral lesions or necrotizing ulcerative periodontitis
• Use of medications known to affect periodontal tissues
• Current smoking
• Presence of immune system disorders or use of immunosuppressive medications
• Presence of prosthetic restorations on teeth selected for gingival crevicular fluid sampling

Individual participant data will not be shared. This study is conducted as a academic thesis and includes sensitive clinical and biochemical data derived from gingival crevicular fluid samples. Although data will be analyzed and reported in aggregate form, sharing individual-level data may compromise participant confidentiality. In addition, institutional and national regulations restrict data sharing without additional ethics approval and explicit participant consent.