Temporal Separation in the Release of Bioactive Molecules from a Moldable Calcium Sulfate Bone Graft Substitute
Matt E. Brown, Yuan Zou, R. Peyyala, Thomas D. Dziubla and David A. Puleo
Affiliation: 522A Robotics and Manufacturing Building, Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506-0108, USA.
Keywords: Bone filler, bone graft substitute, calcium sulfate, composite, moldable, sequential release, simvastatin, vancomycin.
Treatment of infected bone defects presents a considerable challenge due to the complications that occur from
significant bone damage concomitant with contaminated tissue. These wounds are most often treated in a two-step sequence,
where the infection is first eliminated before any attempt to repair the bone is undertaken. In order to combine
these two treatment steps into one procedure, a moldable bone grafting material was developed to deliver drugs in a temporally
separated manner. This was accomplished by a two-layered calcium sulfate composite consisting of a moldable
outer shell containing antibiotic-loaded poly(lactic-co-glycolic acid) microspheres wrapped around a preformed core containing
an osteogenic drug. The release of vancomycin from the shell portion began immediately and continued over the
course of 6 weeks, while the release of simvastatin from the core was delayed for 12 days before being released over the
next 4 weeks. Bioactivity of vancomycin was shown in modified Kirby-Bauer experiments in which whole samples inhibited
Staphylococcus aureus (S. aureus) growth for 2 weeks. This two-layered system is capable of delivering antibiotics
locally for clinically relevant periods of time and delaying the release of osteogenic drugs to mimic a two-step procedure
that has potential for treating infected bone defects.
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