Hierarchically multi-functionalized graded membrane with enhanced bone regeneration and self-defensive antibacterial characteristics for guided bone regeneration

Functional graded nanofibrous membrane (FGM) are gaining great attention in biomedical fields for the reason that it allows tunning the composition, structure, and bioactivity of each layer. Herein, we reported a novel FGM prepared by sequential electrospinning technique to guide bone tissue regeneration. The FGM consisted of two aligned gelatin nanofiber surface layers to improve the biocompatibility and enhance bone regeneration, and a random PCL nanofiber core layer to render the membrane isotropic mechanical strength. To eliminate bacterial infection risk, the pro-metronidazole (Pro-MNA) with infection-responsive release property was synthesized and loaded into the outer layer. The FGM displayed comparable mechanical strength with PCL, and similar biocompatibility to gelatin. The surface aligned nanofiber structure could regulate epithelial cell spread along the aligned direction, instead of infiltration growth, and were more beneficial for the migration and proliferation of osteoblast. In addition, the loaded Pro-MNA displayed infection-responsive release behavior, and robust self-defensive antibacterial function was achieved. These results suggested that the FGM simultaneously fulfil several criteria of biocompatibility, space maintaining capability, antibacterial property, and osteoconductivity. Consequently, the FGM displayed better bone regeneration performance than the commercial Bio-Gide membrane, evaluated by the skull defect model of rabbit. We concluded that the FGM had potential to be used as an ideal GTRM due to its improved overall performance.