Background Perforated barrier membranes (PBM) were suggested to enhance periodontal regeneration by allowing positive charity of wanted elements from the gingival tissue side. The present study was designed to evaluate clinically and biochemically the use of PBM combined with simvastatin (SMV) gel with and without an associated EDTA gel root surface etching as a suggested option that could improve SMV availability and clinical outcomes of PBM. Methods Forty patients having moderate‐to‐severe chronic periodontitis with 40 intrabony defects were randomly divided into four treatment groups (10 sites each). Patients in group 1 received 1.2% SMV gel and covering the defect with occlusive membrane (OM). Patients in group 2 received 1.2% SMV gel and covering the defect with PBM. Group 3 received 24% EDTA root surface etching, 1.2% SMV gel, and defect coverage with OM (eOM). Patients in group 4 were treated as in group 3 but the defect was covered with PBM (ePBM). Clinical parameters were recorded at baseline before surgical procedures and were reassessed at 6 and 9 months after therapy. The mean concentration of SMV in gingival crevicular fluid (GCF) was estimated by reverse‐phase high‐performance liquid chromatography at days 1, 7, 14, 21, and 30. Results At 6‐ and 9‐month observation periods, groups 3 and 4 showed a statistically significant improvement in PD reduction and CAL gain compared with groups 1 and 2. Group 4 showed a statistically significant more defect fill compared with groups 1, 2, and 3 (P ≤ .05). Group 2 showed statistically significant higher defect fill compared with group 1 and group 3 (P < .05). Bone density was significantly increased with no significant difference between the four groups at 6‐ and 9‐month observation periods. SMV‐GCF concentration in group 4 showed the highest mean concentration with no significant difference than that of group 3. Conclusion The use of perforated barrier membranes in association with SMV enhances the clinical hard tissue parameters compared with occlusive ones in treating intrabony periodontal defects. Moreover, EDTA root surface treatment could enhance SMV availability in the defect area.

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