Effect of biological/physical stimulation on guided bone regeneration through asymmetrically porous membrane

Asymmetrically porous polycaprolactone (PCL)/Pluronic F127 guided bone regeneration (GBR) membranes were fabricated. The top surface of the membrane had nanosize pores (∼10 nm) which can effectively prevent invasion by fibrous connective tissue but permeate nutrients, whereas the bottom surface had microsize pores (∼200 μm) which can enhance the adhesiveness with bone tissue. Ultrasound was applied to a bone morphogenetic protein (BMP-2)-immobilized PCL/F127 GBR membrane to investigate the feasibility of using dual biological (BMP-2) and physical (ultrasound) stimulation for enhancing bone regeneration through the membrane. In an animal study using SD rats (cranial defect model), the bone regeneration behavior that occurred when using BMP-2-loaded GBR membranes with ultrasound treatment (GBR/BMP-2/US) was much faster than when the same GBR membrane was used without the ultrasound treatment (GBR/BMP-2), as well as when GBR membranes were used without stimulations (GBR). The enhanced bone regeneration of the GBR/BMP-2/US group can be interpreted as resulting from the synergistic or additive effect of the asymmetrically porous PCL/F127 membrane with unique properties (selective permeability, hydrophilicity, and osteoconductivity) and the stimulatory effects of BMP-2 and ultrasound (osteoinductivity). The asymmetrically porous GBR membrane with dual BMP-2 and ultrasound stimulation may be promising for the clinical treatment of delayed and insufficient bone healing.