Introduction: Periodontal disease causes the progressive loss of supporting structures of the teeth, resulting in bone and soft tissue defects that compromise function and aesthetics. Regenerative periodontal therapy aims to restore these tissues through techniques that stimulate bone and connective tissue regeneration. Among the biomaterials used, Leukocyte- and Platelet-Rich Fibrin (L-PRF) has become widely applied due to its autologous origin, simplicity of preparation, and capacity to release growth factors that promote angiogenesis and wound healing. However, the regenerative potential of new bioactive materials such as REGENFAST®, a combination of polynucleotides and hyaluronic acid, has recently gained attention. Polynucleotides act as biological stimulators that enhance fibroblast activity and tissue oxygenation, while hyaluronic acid improves extracellular matrix remodeling and hydration. Although preclinical data suggest beneficial effects of REGENFAST® in soft and hard tissue repair, direct clinical comparisons with L-PRF in periodontal regeneration remain limited.

Objectives: The main objective is to evaluate and compare the clinical and radiographic efficacy of REGENFAST® and L-PRF in the treatment of bilateral periodontal defects.

Specific objectives include:

• Assessing the gain in clinical attachment level (CAL) at 3 months postoperatively as the primary outcome.
• Comparing changes in probing depth, gingival recession, bleeding on probing, and gingival inflammation index.
• Evaluating wound healing using the Landry Healing Index and recording total surgical and epithelialization times.
• Assessing radiographic bone density changes between baseline and 3 months. Patient inclusion will be based on predefined inclusion and exclusion criteria to ensure homogeneity and comparability.

Material and methods: A randomized, split-mouth pilot clinical trial will be conducted in patients presenting bilateral periodontal defects. Each subject will receive REGENFAST® on one site and L-PRF on the contralateral site, assigned by computer-generated randomization. Following local anesthesia, full-thickness flaps will be raised, and defects will be debrided and conditioned. The respective biomaterial will then be applied, and the flaps will be repositioned and sutured. Postoperative evaluations will occur at 7 days, 1 month, and 3 months, recording clinical parameters and radiographic outcomes. Data will be analyzed using paired t-tests with a significance level of p<0.05. The study will adhere to the Declaration of Helsinki and Good Clinical Practice guidelines, with informed consent obtained from all participants.

Inclusion Criteria:

• Adult patients (≥18 years old) in good general health (ASA I-II).
• Bilateral gingival recessions or symmetrical bone defects.
• Absence of active infection or inflammation.
• Good oral hygiene level (Plaque Index <20%).
• Signed informed consent and commitment to follow-up.

Exclusion Criteria:

• Systemic diseases that impair healing (uncontrolled diabetes, immunodeficiency, etc.).
• Periodontal or antibiotic treatment within the last 6 months.
• Smokers (>10 cigarettes/day).
• Pregnancy or breastfeeding.
• Allergy or hypersensitivity to REGENFAST® or surgical materials.
• Use of medication affecting healing (corticosteroids, immunosuppressants, bisphosphonates).
• Lack of availability to attend follow-up visits.

The investigators will anonymize and categorize the clinical data of the patients to share the information with the other researchers of the group.

The patient will be unaware of which site receives REGENFAST® or L-PRF, while the clinician performing the procedure will know the allocation. This ensures that patient-reported outcomes, such as pain and satisfaction, are not biased by knowledge of the treatment received.