Bone morphogenetic protein delivery systems.

Abstract

STUDY DESIGN: A review was conducted. OBJECTIVES: To review the rationale for the use of carrier systems to deliver bone morphogenetic proteins to sites of orthopedic repair, and to discuss commonly used carriers. SUMMARY OF BACKGROUND DATA: Carriers for bone morphogenetic protein in spine fusion are used to increase the retention of these osteogenic factors at the treatment site, and to serve as an osteoconductive matrix for bone forming cells while maintaining a space or volume in which bone formation can occur. METHODS: The literature is reviewed and discussed. RESULTS: Although bone morphogenetic proteins can induce bone formation when delivered in formulation buffer in small animal models, carriers often are used in larger animal models and human clinical trials to maintain the concentration of osteogenic factors at the treatment site for a sufficient period to allow bone-forming cells to migrate to the area of injury and to proliferate and differentiate. For spine fusion, carriers also are required to serve as an osteoconductive matrix for bone-forming cells while maintaining a space or volume in which bone formation can occur. Four major categories of carrier materials are used for osteogenic factor delivery: inorganic materials, synthetic polymers, natural polymers, and composites of the first three materials. In addition, allograft bone has been used to deliver osteogenic factors to the site of orthopedic repairs. The efficacy of osteogenic carrier combinations often is site specific and species specific. The requirement for supraphysiologic concentrations of osteogenic factors may be related to the ability of the delivery system to increase the retention time at the treatment site and overcome tight regulation of these factors by their inhibitors. Dose escalation in large animal models also may be related to a decrease in the number of responding cells and a slower rate of bone formation. New delivery systems being evaluated include depot delivery systems, viral vector systems, conjugated osteogenic factor delivery systems, and oral small molecule targets. CONCLUSIONS: Delivery systems play an important role in the use of osteogenic factors to augment spine fusions and other orthopedic repairs.