The use of Enamel Matrix Derivative (EMD) associated to microsurgical flaps was demonstrated to be effective for the treatment of intrabony defects, in particular in presence of a self-contained anatomy. The main aim of this study will be to evaluate the difference in Clinical Attachment Level (CAL) between baseline and 1-year follow-up, comparing flapless periodontal regeneration using EMD versus the use of EMD after microsurgical flap elevation (Modified-Minimally Invasive Surgical Technique (M-MIST) / Single-flap approach).

The secondary aims of the study are:

• to evaluate the comparative effectiveness of the proposed treatment evaluating patient-centered outcomes.
• to evaluate, after one year from the treatment, the comparative effectiveness evaluating clinical parameters: (I) Probing Depth (PD) measured from the gingival margin to the base of the pocket; (II) Recession (REC) measured as the distance between the CEJ and the gingival margin; (III) Presence of plaque in the site of intervention, measured dichotomously (Yes / No) (Plaque index (PI)); (IV) Presence of bleeding in the site of intervention, measured dichotomously (Yes / No) (Bleeding Index (BI)); (V) Full-mouth Bleeding Score (FMBS%); (VI) Full-mouth Plaque Score (FMPS%); (VII) the proportion of treated sites for each group that presented PD <= 3 mm. ; (VIII) tooth retention
• to evaluate the comparative effectiveness evaluating radiographic parameters: (I) The distance between the Cemento-Enamel Junction (CEJ) and the bottom of the defect (CEJ-A) (II) the distance between the projection of the bone crest to the root surface and the bottom of the defect (representing the intrabony portion of the defect (III) C-A), and the distance between the bone crest and the root surface (representing the maximum width of the defect, C-B) were measured.

Control group: A buccal flap extending to the surfaces of the adjacent teeth will be elevated leading the interdental papilla in position following the M-MIST approach. After degranulation of the defect EMD will be applied following the standard procedure (after preparing root surface with Ethylenediamine tetraacetic acid (EDTA) 22% for two minutes). Non-resorbable 6/0 sutures will be used. The whole procedure will be performed using magnification devices (surgical loupes or surgical microscope). The operator will give postoperative instructions and information about medication.

Test group: The debridement of the pocket will be performed without the elevation of the flap, using ultrasonic tips, air polishing devices and curettes as standard procedure. After that, EMD will be applied and the same procedures as control group will be carried out. Non-resorbable 6/0 sutures will be used in the site of surgical intervention to close coronally the pocket.

At 7 days, suture removal, collection of questionnaires and clinical evaluation will be performed.

Follow-up visits will be carried out at 3, 6, 12, 18 and 24 months.

Inclusion Criteria:

• Men and women over or equal to the age of 18 years
• Patients who are able to understand the requirements of the study and are willing and able to comply with its instructions and schedules
• Patients who had provided written informed consent to participate in the study prior to any study procedure
• Patients in general good health in the opinion of the principal investigator as determined by medical history and clinical examination (American Society of Anesthesiologists ASA 1 or ASA-2)
• Patients having one or more self-contained (3-wall or 2-3 walls) intrabony periodontal defect with an intrabony component of equal or more than 3 mm, as diagnosed by periapical radiographs and clinical evaluation.

Exclusion Criteria:

• FMPS% > 15%
• FMBS% > 15%
• Treatment with anticoagulant drugs (International Normalized Ratio (INR) above 2,5)
• Treatment with intravenous bisphosphonates
• Treatment with anticonvulsants drugs
• untreated Periodontal disease and inability of the patient to maintain reasonable oral hygiene according to study requirements
• Patients with history of alcohol, narcotics or drug abuse
• Patients receiving radiotherapy, chemotherapy or any other immunosuppressive treatment or who have been administered radiotherapy in the last 5 years
• Patients through at any time received radiotherapy to the head and neck region will be excluded anyway
• Uncontrolled bleeding disorders such as: hemophilia, thrombocytopenia, granulocytopenia
• Degenerative diseases
• Osteoradionecrosis
• Renal failure
• Organ transplant recipients
• HIV positive (self-declaration)
• Malignant diseases
• Diseases that compromise the immune system
• Unbalanced diabetes (HbA1c above 7.2 assessed by self-declaration)
• Psychotic diseases
• Hypersensitivity or specific contraindications to one of the components of EMD
• Women who are pregnant (self-declaration); or lactating at the time of recruitment and of surgery
• Site where a history of failed periodontal regenerative procedure in the last two years
• Heavy Smokers (10 cigarettes and more per day).