Multifunctional Biomimetic GTR Membrane For Bone Regeneration In Inflammatory Microenvironment

Aim or purpose: Commercially available barrier membranes for guided tissue regeneration (GTR) often lack suitable mechanical properties, controllable degradation rate, and sufficient bioactivity, which would lead to unsatisfied bone regeneration capacity, thereby being unable to fulfill the demands of oral clinical treatment. Materials and methods: The multifunctional biomimetic GTR membrane composed of a dense layer and a porous layer was fabricated by emulsion template method: The dense layer with a stable structure acts as an effective physical barrier preventing the soft tissue from invading the bone defect areas; The porous layer functionalized by the DP7-C/miR-26a complex would promote efficient bone regeneration by regulating immune microenvironment. The physicochemical characterization of membranes were measured by SEM, universal mechanical testing machine and UV-vis spectrophotometer. The in vitro bioactivities of macrophage polarization and BMSCs differentiation were evaluated through flow cytometry, Western blot, qPCR and immunofluorescence. The in vivo therapeutic efficacy was also validated by the rat periodontitis model through micro-CT analysis, H&E staining, and immunohistochemical. Results: The membrane possesses heterogeneous bilayer microstructures, strain maintenance ability, good degradation property, and well biocompatibility. In vitro, it redirected macrophages toward regenerative M2 polarization (CD206↑/TNF-α↓/IL-10↑) while potentiating BMSCs osteogenesis via upregulated RUNX2/OCN expression and accelerated mineralization. The micro-CT reconstruction confirmed significant mitigation of alveolar bone destruction in vivo. Conclusions: In this study, the multifunctional biomimetic GTR membrane was developed to achieve rapid and efficient bone regeneration in inflammatory microenvironment, providing new means for oral clinical treatment of inflammatory bone defects.