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.