Efficacy of positive space acquiring membrane and antimicrobial membrane combined with granular bone substitute implantation in guiding oral bone regeneration.

Augmentation of the alveolar bone is important before oral implantation. For large bone defects, it becomes necessary to apply guided bone regeneration (GBR) materials, accompanied by filling defect sites with autologous or allogeneic bone, or bone substitutes such as acellular bone powder. In this study, we tested a granular bone substitute and GBR membrane combination therapy in treating MC3T3-E1 and L929 cells in vitro and rat calvarial and alveolar defects in vivo. The recovery conditions of bone defects were monitored by micro-CT, and 3D reconstruction of the CT images was applied to evaluate the bone augmentation semi-quantitatively. Test GBR materials could support the proliferation of MC3T3-E1 cells, poly (p-dioxanone-co-L-phenylalanine) (PDPA)-based membrane could induce apoptosis of L929 cells. Among GBR membranes applied groups, the regeneration condition of defected calvarial defects of PDPA based membrane applied group was the best and this may be caused by its excellent positive space acquiring effect. However, in a complex bacteriogenic environment, the oral bone regeneration-guided efficacy of the PDPA membrane decreased in the post-repair stage with the aggravation of infections. By contrast, the antimicrobial membrane combined with the PDPA membrane exhibited continually increasing GBR efficacy at the later stage of repair owing to its multifunctional properties, which are infection-inhibiting and positive space acquiring. Therefore, multifunctional GBR membranes are preferable for GBR in complex oral environments, and further research should be conducted to determine their efficacy in other models.

Positive space acquiring asymmetric membranes for guiding alveolar bone regeneration under infectious conditions.

To obtain multifunctional materials suitable for guiding alveolar bone regeneration under infectious conditions, we prepared asymmetric membranes comprising space acquiring layer that involves fibroblast inhibitor poly(p-dioxanone-co-L-phenylalanine) (PDPA), an isolating dense layer that forms barrier between two layers and an osteogenesis inducing electrospinning layer which involves hydroxyapatite or hydroxyapatite & minocycline. Then the composition, crystallization, morphology, and hydrophilicity of asymmetric membranes were analyzed. Minocycline incorporated membranes controlled the expansion of Porphyromonas gingivalis (P. gingivalis) in vitro. Hydroxyapatite-incorporated asymmetric membranes promoted the expression of osteogenesis related genes RUNX2, OPN, ALP of MC3T3-E1 cells in vitro. The mineralization of MC3T3-E1 cells cultured with hydroxyapatite-incorporated asymmetric membranes were also promoted in vitro. Asymmetric membranes especially hydroxyapatite-incorporated ones guided the regeneration of the mandibular bone defect in vivo. Bone regeneration guided under infectious conditions was evaluated in a P. gingivalis infected alveolar bone defect model. Specifically, space acquiring layer containing asymmetric membranes effectively controlled connective tissue hyperplasia at defect sites. The excellent guided bone regeneration achieved by applying a single space acquiring layer membrane further indicates the importance of acquiring space actively to induce bone regeneration. Hydroxyapatite-minocycline incorporated symmetric membranes could simultaneously suppress alveolar bone reabsorption caused by infection and guide regeneration of defects. Therefore, the hydroxyapatite-minocycline incorporated asymmetric membrane may be more suitable to be applied in guiding regeneration of bone defects under complex infectious conditions.