The Role of Granulation Tissue in Periodontal Regeneration

Inclusion Criteria: 1. Both genders. 2. Systemically healthy. 3. Both smokers (smoking at least 10 cigarettes a day or electronic cigarettes daily or quit less than 5 years ago) and non-smokers (never smoked, smoke no more than once a month or quit at least 5 years ago). 4. Patients aged 18 years and over. 5. Patients with a history of severe periodontitis (stage III or IV, grade B-C) and, after completion of the non-surgical stage of periodontal treatment with at least one residual vertical bone defects (with ≥3 mm infrabony component) in premolar-molar region. 6. Patients with a plaque index and bleeding on probing of 20% or lower before surgery. Exclusion Criteria: 1. Systemic diseases that may affect study results (uncontrolled type 2 diabetes mellitus (HBA1c level of \>7%); recent (less than 6 months ago) myocardial infarction or stroke; blood coagulation disorders; recent use of antibiotics (less than 6 months). 2. Use of medications that may affect study results (anti-osteoporotic drugs, statins, corticosteroids, calcium channel blockers, cyclosporine A, antiepileptic drugs, antipsychotic medication or antidepressants, chemotherapy and/or radiotherapy (active or history)). 3. Current pregnancy and/or breastfeeding. 4. Patients who have received any form of systemic antibiotics in the last six months prior to the start of the study. 5. Patients who require antibiotic premedication prior to periodontal treatment. 6. Prosthetic factors in teeth associated with suitable bone defects that prevent clinical measurements. 7. Lack of patient motivation to undertake adequate dental care at home or to complete periodontal treatment. 8. Strong vomiting reflex preventing adequate periodontal treatment.