Nano Twin-Fiber Membrane with Osteogenic and Antibacterial Dual Functions as Artificial Periosteum for Long Bone Repairing

Due to the significant role of the periosteum in bone regeneration, we fabricated a novel twin-fiber membrane with antibacterial and osteo-inductive properties as an artificial periosteum by a double spinneret electrospinning method. The antibacterial drug moxifloxacin (MOX) and Chinese medicine icariin (ICA) were introduced into PCL/gelatin and PCL micro/nano fibers respectively to endow the membrane with antibacterial and osteoinduction properties. The twin-fiber structure membrane not only acted as carriers for two different drugs with drastically different solubility in the same fiber membrane, but also achieved stepwise and controlled drug release profiles based on different degradation rates of the two fibers matrix and diffusion rates of the two drugs. Most importantly, only 35% ICA was released out from this dual drug loaded membrane after 1 month and such slow release rate would match with the bone regeneration rate which can hardly be achieved by other drug delivery system. Besides, this dual drug loaded twin-fiber membrane exhibited clear antibacterial effect and excellent in vitro biocompatibility for cells to adhere to and proliferate on. Furthermore, an obvious up-regulation of osteocalcin (OCN), type I collagen (COLI) expression and calcium deposition of MC3T3-E1 cells demonstrated the improved osteogenic differentiation capability. Also, the dual drug loaded twin-fiber membrane displayed fascinating properties contributing to new bone formation in rabbit radius defect model. These results indicate the huge potential of this dual drug loaded twin-fiber membrane as an effective drug release controller and biomimetic multifunctional artificial periosteum to accelerate bone regeneration.