The Influence of Delivery Vehicles and Their Properties on the Repair of Segmental Defects and Fractures with Osteogenic Factors

Abstract

Normal fracture-healing involves a number of osteogenic factors that are released from bone and the surrounding soft tissues during the repair process. Osteogenic factors are involved in a number of processes related to bone formation and bone-remodeling, including chemotaxis, proliferation, and differentiation of bone-forming and bone-remodeling cells, blood vessels, nerves, and marrow elements. Local release of physiologic quantities of these osteogenic factors is generally sufficient to elicit fracture repair. Considerable effort has been expended in an attempt to accelerate fracture repair and to increase the assurance of healing by the exogenous application of these osteogenic factors. Similar efforts have been made to bridge critical-sized segmental defects and nonunions with the use of osteogenic factors. Determining the appropriate delivery vehicle for local application of these factors has been one of the major limitations to the success of these therapies. In addition, supraphysiologic doses of osteogenic factors appear to be required to achieve satisfactory results. Since the endogenous release of physiologic levels of osteogenic factors does not require a delivery vehicle for fracture repair, why is a delivery system required for exogenous delivery and why are the required doses so high? The answers to these questions may be related to the type of orthopaedic repair being attempted and the animal model being studied. The role of delivery vehicles for osteogenic factors is best understood in the context of bridging critical-sized defects. These defects by definition do not heal spontaneously. One of the primary roles of the delivery vehicle in this type of repair is to maximize the osteogenic effect of the delivered factors by maintaining these factors at the site of implantation and optimizing their release profile. Another important role of the delivery vehicle is to serve as an osteoconductive matrix for bone-forming cells while maintaining a space or volume in which …