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

Abstract

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.

Freeze-Drying Process for the Fabrication of Collagen-Based Sponges as Medical Devices in Biomedical Engineering

“…Moreover, the implants should exhibit other desired properties, such as biocompatibility and biodegradability, as well as the ability to promote cell adhesion, cell proliferation, and differentiation for the formation of new tissue [ 66 , 67 ]. Cells are able to recognize the texture and arrangement of the implant; therefore, even topographical anisotropies have to be considered [ 68 ]. Freeze drying is one of the main available processes for the development of medical devices in the form of collagen-based, sponge-like implants for tissue regeneration, such as bone, muscle, cartilage, skin, and nerve tissue [ 41 , 69 , 70 , 71 , 72 ].…”