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Collagen membranes cross-linked by glycation (GLYM) for guided bone regeneration (GBR) and guided tissue regeneration (GTR) are used extensively with proven safety and efficacy. Complete GLYM ossification, when placed in contact with bone, was described in a canine jaw model, suggesting that GLYM may serve as an ossification substrate. The purpose of this case series was to histologically evaluate GLYM in GBR procedures in humans.We retrospectively selected seven consecutive patients with implant-related bony defects who underwent GBR with GLYM. Six defects had bone grafts, and one had a barrier alone. Selection criteria were primary closure upon post-surgical examination and tissue that was 2- to 3-mm thick over the implant's cover screw. Tissue was removed when the implants were uncovered after20 to 29 weeks. Decalcified sections were stained and analyzed under light microscopy.In five of seven specimens, GLYM was identified and preserved its barrier effect. The mean membrane thickness was 0.17 ± 0.054 mm. In two cases, the bone grafts under the membrane were embedded in new bone, whereas in five cases, they were embedded in fibrous connective tissue. Formation of new dense bone was observed along the side of the membrane facing the original bone, and various degrees of membrane ossification were evident in all five cases.GLYM maintained its barrier effect in five of seven cases for 25 weeks and induced dense new bone along its interface with underlying tissues. To the best of our knowledge, this is the first report on GLYM ossification in humans with direct mineral apposition on glycated collagen and suggests a new concept of tissue-integrated active barriers. J Periodontol 2008;79:1101–1107.