A resorbable antibiotic eluting bone void filler for periprosthetic joint infection prevention.
Periprosthetic joint infection (PJI) following total knee arthroplasty is a globally increasing procedural complication. These infections are difficult to treat and typically require revision surgery. Antibiotic-loaded bone cement is frequently utilized to deliver antibiotics to the site of infection; however, bone cement is a nondegrading foreign body and known to leach its antibiotic load, after an initial burst release, at subtherapeutic concentrations for months. This work characterized a resorbable, antibiotic-eluting bone void filler designed to restore bone volume and prevent PJI. Three device formulations were fabricated, consisting of different combinations of synthetic inorganic bone graft material, degradable polymer matrices, salt porogens, and antibiotic tobramycin. These formulations were examined to determine the antibiotic's elution kinetics and bactericidal potential, the device's degradation in vitro, as well as osteoconductivity and device resorption in vivo using a pilot rabbit bone implant model. Kirby-Bauer antibiotic susceptibility tests assessed bactericidal activity. Liquid chromatography with tandem mass spectrometry measured antibiotic elution kinetics, and scanning electron microscopy was used to qualitatively assess degradation. Results indicated sustained antibiotic release from all three formulations above the Staphylococcus aureus minimum inhibitory concentration for a period of 5 to 8 weeks. Extensive degradation was observed with the Group 3 formulation after 90 days in phosphate-buffered saline, with a lesser degree of degradation observed in the other two formulations. Results from the pilot rabbit study showed the Group 3 device to be biocompatible, with minimal inflammatory response and no fibrous encapsulation in bone. The device was also highly osteoconductive-exhibiting an accelerated mineral apposition rate. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1632-1642, 2016.
Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112.
Zachary
Z
Jones
Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112.|Elute Inc, Salt Lake City, Utah, 84108.
Amanda E
AE
Brooks
Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112.
Zachary
Z
Ferrell
Department of Bioengineering, University of Utah, Salt Lake City, Utah, 84112.|Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, 84112.
David W
DW
Grainger
Elute Inc, Salt Lake City, Utah, 84108. kristofer.sinclairkristof@gmail.com.
Kristofer D
KD
Sinclair
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology; D000069343:Bone-Implant Interface / Q000254:growth & development* / Q000382:microbiology* / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013211:Staphylococcus aureus; D014031:Tobramycin / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D018786:Bone Substitutes; D004337:Drug Carriers; D014031:Tobramycin
controlled drug release; osteomyelitis; preclinical rabbit animal model; tobramycin; total joint revision