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The present study was designed to determine whether exclusion of the gingival connective tissue (CT) and periosteum with contained stem cells has a positive or negative effect on periodontal regeneration by comparing the use of a novel modified perforated collagen membrane with a traditional cell occlusive barrier membrane.Twenty non-smoking patients with severe chronic periodontitis were included in the study. Single deep intrabony defects from each of the patients were randomly divided into two groups, as follows: occlusive bovine collagen membranes (OM control group, 10 sites) and modified perforated bovine collagen membranes (MPM test group, 10 sites). Plaque index, gingival index, probing depth (PD), clinical attachment level (CAL), defect base level (DBL), and crestal bone level (CBL) were measured at baseline and were reassessed at 6 and 9 months after therapy to evaluate the quantitative changes in the defect.At 6- and 9-month observation periods, the MPM-treated sites showed a statistically significant improvement in PD reduction and CAL gain compared with the OM control group. DBL was significantly reduced with no significant difference between the two groups at 6- and 9-month observation periods. CBL was significantly higher in the MPM group when compared with that of the OM group at both observation periods. The postoperative differences between the two groups were 2 and 1.7 mm at 6 and 9 months, respectively, in favor of the MPM-treated sites.The present study demonstrated enhanced clinical outcomes when using novel MPMs compared to OMs in guided tissue regeneration procedures. These results may be affected by the penetration of gingival CT contained stem cells and periosteal cells and their differentiation into components of the attachment apparatus.