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.
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