ABSTRACT

Since Marshall Urist first described the discovery of osteogenic proteins (1), there has been an increasing interest in the application of osteoinductive cytokines to simulate de novo bone formation in orthopaedic applications. As spine fusion is the most common bone grafting procedure (2), significant work has been done investigating the utility of various osteoinductive proteins for this purpose (3-13). Chief among these proteins are the bone morphogenetic proteins (BMPs). These proteins have been produced either by extracting and purifying them from animal or human cortical bone, or through recombinant techniques (2). As researchers studied the ability of various BMP preparations to form bone at the site of experimental fractures, segmental defects, and ultimately spine fusions, it became clear that a critical component of osteoinduction was the method of delivery of these proteins. When applied to an experimental fracture site in a small animal model, BMP could effectively be delivered by simply injecting the growth factor at the site in formulation buffer (14,15). However, this was not the case when BMP was used either in a higher animal model or in a more challenging model such as healing a critical-sized cortical defect, or in spine fusion (15,16). In these instances, the delivery method of the BMP became more critical and complex. This was for a variety of reasons related to the local environment in which the protein was applied and the conditions necessary for successful bone formation and healing. As the clinical success of these cytokines is often predicated on successful delivery, much investigation has been done to evaluate different delivery systems or carriers (3-5,8,9,12,15-17). This Chapter will discuss the various characteristics required of an effective carrier as well as the specific carriers being evaluated both clinically and experimentally.