Formulation, Delivery and Stability of Bone Morphogenetic Proteins for Effective Bone Regeneration.

Bone morphogenetic proteins (BMPs) are responsible for bone formation during embryogenesis and bone regeneration and remodeling. The osteoinductive action of BMPs, especially BMP-2 and BMP-7, has led to their use in a range of insurmountable treatments where intervention is required for effective bone regeneration. Introduction of BMP products to the market, however, was not without reports of multiple complications and side effects. Aiming for optimization of the therapeutic efficacy and safety, efforts have been focused on improving the delivery of BMPs to lower the administered dose, localize the protein, and prolong its retention time at the site of action. A major challenge with these efforts is that the protein stability should be maintained. With this review we attempt to shed light on how the stability of BMPs can be affected in the formulation and delivery processes. We first provide a short overview of the current standing of the complications experienced with BMP products. We then discuss the different delivery parameters studied in association with BMPs, and their influence on the efficacy and safety of BMP treatments. In particular, the literature addressing the stability of BMPs and their possible interactions with components of the delivery system as well as their sensitivity to conditions of the formulation process is reviewed. In summary, recent developments in the fields of bioengineering and biopharmaceuticals suggest that a good understanding of the relationship between the formulation/delivery conditions and the stability of growth factors such as BMPs is a prerequisite for a safe and effective treatment.