title: Molded polymer-coated composite bone void filler improves tobramycin controlled release kinetics.
abstract: Infection remains a significant problem associated with biomedical implants and orthopedic surgeries, especially in revision total joint replacements. Recent advances in antibiotic-releasing bone void fillers (BVF) provide new opportunities to address these types of device-related orthopedic infections that often lead to substantial economic burdens and reduced quality of life. We report improvements made in fabrication and scalability of an antibiotic-releasing polycaprolactone-calcium carbonate/phosphate ceramic composite BVF using a new solvent-free, molten-cast fabrication process. This strategy provides the ability to tailor drug release kinetics from the BVF composite based on modifications of the inorganic substrate and/or the polymeric component, allowing extended tobramycin release at bactericidal concentrations. The mechanical properties of the new BVF composite are comparable to many reported BVFs and validate the relative homogeneity of fabrication. Most importantly, fabrication quality controls are correlated with favorable drug release kinetics, providing bactericidal activity to 10 weeks in vitro when the polycaprolactone component exceeds 98% w/w of the total polymer fraction. Furthermore, in a time kill study, tobramycin-releasing composite fragments inhibited S. aureus growth over 48 h at inoculums as high as 10(9) CFU/mL. This customizable antibiotic-releasing BVF polymer-inorganic biomaterial should provide osseointegrative and osteoconductive properties while contributing antimicrobial protection to orthopedic sites requiring the use of bone void fillers.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84112-5820.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Brooks
authors.forename: Kristofer D
authors.initials: KD
authors.lastname: Sinclair
authors.forename: Sherry N
authors.initials: SN
authors.lastname: Davidoff
authors.forename: Scott
authors.initials: S
authors.lastname: Lawson
authors.forename: Alex G
authors.initials: AG
authors.lastname: Williams
authors.forename: Brittany
authors.initials: B
authors.lastname: Coats
authors.forename: David W
authors.initials: DW
authors.lastname: Grainger
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Brooks
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018786:Bone Substitutes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002130:Calcium Phosphates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002516:Ceramics / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000254:growth & development*; D014031:Tobramycin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D018786:Bone Substitutes; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D011091:Polyesters; C016240:polycaprolactone; C020243:calcium phosphate; D014031:Tobramycin
keywords: bone void filler; controlled release; implant infection; joint replacement; osteomyelitis; polycaprolactone; revision surgery; tobramycin