Berberine Loaded‐Mineralized Bilayer Membranes Enhance Osteogenic Differentiation and Promote Calvarial Defects Regeneration

The calvarial defects are difficult to repair and often lead to severe calvarial deformity and dysfunction. There is an urgent need to develop biomimetic bone tissue engineering materials for the repair of the calvarial defect. Berberine/polycaprolactone/polyvinylpyrrolidone‐mineralized collagen/chitosan (BBR/PCL/PVP‐MC/CS) bilayer membranes were prepared using electrostatic spinning combined with cast film technology. Using rat bone marrow‐derived mesenchymal stem cells (rBMSCs), we analyzed the in vitro biocompatibility and osteogenic potential of the membranes. Bone regeneration in vivo was assessed in the rat calvarial defects model. Bilayer membranes showed a highly porous three‐dimensional structure, enabling slow, sustained release of BBR for up to 25 days. Compared with PCL/PVP‐MC/CS bilayer membranes, BBR/PCL/PVP‐MC/CS bilayer membranes significantly enhanced the adhesion, proliferation, migration, and osteogenic differentiation of rBMSCs. Expression of the osteogenic genes RUNX2 , ALP , and OCN were significantly increased. BBR/PCL/PVP‐MC/CS bilayer membranes implanted for 8 weeks were almost completely degraded, and rat calvarial defects were largely repaired. These promising results suggest the effects of BBR and MC significantly promote the osteogenic differentiation of rBMSCs and the repair of calvarial defects; BBR/PCL/PVP‐MC/CS bilayer membranes are deemed a strong potential candidate for the repair of calvarial defects.