Carrier systems for bone morphogenetic proteins.

Abstract

Bone deficits can regenerate inherently, although when the amount of bone loss exceeds a critical limit, pseudarthrosis and fibrosis occur. Therapeutic intervention either with an autograft or allogeneic bank bone are traditional options to promote regeneration to overcome critical limits. However, liabilities with traditional treatments have inspired investigators to develop alternatives, such as combinations of biomimetic scaffolds and osteogenic regulatory molecules. The class of osteogenic regulatory molecules known as the bone morphogenetic proteins has several members that stimulate bone regeneration. Therapeutic applications of bone morphogenetic proteins require a well characterized carrier system to ensure safe and effective presentation at the implant site. Several carrier systems have been used to evaluate the sustained release and implant retention of recombinant human bone morphogenetic protein-2. The carrier systems used in this study include type I collagen, poly(D,L-lactide), and deorganified bovine bone. Pharmacokinetics of recombinant human bone morphogenetic protein-2 released from these systems were characterized in the rat ectopic assay. Pharmacokinetics were influenced by the implant carrier. For example, sustained release occurred with the collagen sponge. The recombinant human bone morphogenetic protein-2 from deorganified bovine bone resulted in a burst release at the first collection interval, but thereafter, appeared to bind irreversibly to the morphogen. The poly (D,L-lactide) systems showed a dose dependent sustained release pattern. These results indicate the physicochemical characteristics of a carrier system for recombinant human bone morphogenetic protein-2 impact the release kinetics and may have a profound influence on clinical outcome.