title: Temporal separation in the release of bioactive molecules from a moldable calcium sulfate bone graft substitute.
abstract: 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.
authors.forename: Matt E
authors.initials: ME
authors.lastname: Brown
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zou
authors.forename: R
authors.initials: R
authors.lastname: Peyyala
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dziubla
authors.affiliation: 522A Robotics and Manufacturing Building, Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506-0108, USA. puleo@uky.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Puleo
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D018786:Bone Substitutes / Q000737:chemistry*; D002133:Calcium Sulfate / Q000737:chemistry*; D065546:Drug Liberation; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D018786:Bone Substitutes; D002133:Calcium Sulfate