AIM: To evaluate whether the ribosome-crosslinked collagen membrane (RCCM) is non-inferior to the natural collagen membrane (NCM) used in regeneration surgery in terms of clinical attachment level (CAL) gain at 6 months. METHODS: Eighty patients diagnosed as generalized periodontitis presenting with isolated infrabony defect (≥4 mm deep) were enrolled and randomized to receive regenerative surgery, either with NCM or RCCM, both combined with deproteinized bovine bone mineral (DBBM). CAL, pocket probing depth (PPD), and gingival recession (GR) were recorded at baseline, 3, and 6 months postoperatively. Periapical radiographs were taken at baseline, immediately, and 6 months after surgery. Early wound healing index (EHI) and patients' responses were recorded at 2 weeks postoperatively. RESULTS: At 6 months post-surgery, the mean CAL gain was 3.1 ± 1.5 mm in the NCM group and 2.9 ± 1.5 mm in the RCCM group, while the mean PPD was 4.3 ± 1.1 mm in the NCM group and 4.2 ± 1.0 mm in the RCCM group. Both groups demonstrated a statistically significant improvement from the baseline (p <
.01). RCCM was non-inferior to NCM concerning the primary outcome (CAL gain at 6 months). The GR at 6 months postoperatively was 1.3 ± 1.2 and 1.2 ± 1.1 mm, which showed no difference compared with baseline. At 6 months follow-up, the radiographic linear bone fill (RLBF) was 6.5 ± 2.8 and 5.5 ± 2.6 mm (p >
.05), while the bone fill percentage (BF%) was 102.3 ± 53.5% and 92.3 ± 40.1% (p >
.05), in the NCM and RCCM groups, respectively. There was no significant difference in EHI and postoperative responses between two groups. CONCLUSION: RCCM + DBBM resulted in no-inferior clinical and radiographic outcomes to NCM + DBBM for the treatment of isolated infrabony defect in 6 months.