To date, the quest for ideal biological inductors for periodontal regeneration is still ongoing, especially when facing non-containing defect anatomies. The primary aim of this study is to evaluate the clinical and radiographic performance of a bone graft combined with either enamel matrix derivatives or hyaluronic acid for periodontal regeneration of non-containing intrabony defects in terms of clinical attachment gain (primary outcome) and other secondary outcomes (probing pocket depth reduction, radiographic bone fill). Moreover, this study aims to compare early wound healing and patient-reported outcome measures.

Inclusion criteria:

• Diagnosis of stage III-IV periodontitis.
• Completed steps I-II periodontal therapy.
• FMPS <15% at 3-month re-evaluation.
• FMBS <15% at 3-month re-evaluation.
• At least one site with intrabony defects and residual PPD ≥ 6 mm at re-evaluation, with a radiographic intrabony component ≥ 3 mm, and limited to no extension of the defect on the lingual or palatal side as assessed by preoperative bone sounding.
• Intrasurgically, the defect has to present a non-supporting anatomy (1-2 residual walls in its most coronal portion) and it needs to be accessible by flap elevation only on one side (either buccal or oral).
• Signed informed consent.

Exclusion criteria:

• Compromised general health which contraindicates the study procedures (ASA III-VI patients).
• Systemic diseases/medications which could influence the outcome of the therapy (e.g. uncontrolled diabetes mellitus, non-plaque-induced gingival diseases, antiepileptic drugs (phenytoin and sodium valproate), certain calcium channel-blocking drugs (e.g., nifedipine, verapamil, diltiazem, amlodipine, felodipine), immunoregulating drugs (e.g., ciclosporine), and high-dose oral contraceptives).
• Current smokers (self-reported, ≥ 10 cigarettes a day), users of chewing tobacco, and drug/alcohol abusers.
• Pregnant or nursing women.
• Presence of furcation involvement ≥ II degree (Hamp 1975) at the affected teeth.