Improving the handling properties and long‐term stability of polyelectrolyte complex by freeze‐drying technique for low‐dose bone morphogenetic protein 2 delivery

A variety of controlled release carriers for bone morphogenetic protein 2 (BMP‐2) delivery have been developed and tested in animal models. An alginate‐based polyelectrolyte complex (PEC) for controlled release of low‐dose BMP‐2 has shown promising results in preclinical research. However, the poor handling properties and long‐term stability of PEC need to be improved for translational applications. This study aimed to address these limitations of alginate‐based PEC by employing a freeze‐drying technique. The size and structure of freeze‐dried PEC (FD‐PEC) were maintained with the addition of a cryoprotectant, trehalose. The release profile of BMP‐2 from FD‐PEC was similar to that of freshly prepared PEC. In vitro bioactivity analysis of the released BMP‐2 showed that the carrier performance of PEC was not compromised by freeze‐drying up to three‐month storage at room temperature. BMP‐2‐bound FD‐PEC induced comparable bone formation to that using freshly prepared regular PEC in a rat posterolateral spinal fusion model. These results suggest that FD‐PEC is capable of delivering low‐dose BMP‐2 and could be developed as an off‐the‐shelf product for translational applications. The simplicity of this preservation method provides promise for the translational application of PEC.