Testing of a bioactive, moldable bone graft substitute in an infected, critically sized segmental defect model

Matt E. Brown, Yuan Zou, Rebecca Peyyala, Sarandeep S. Huja, Larry L. Cunningham, Todd A. Milbrandt, Thomas D. Dziubla, David A. Puleo

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Large infected bone defects, often resulting from high energy traumas, are difficult to treat due to their variability in complexity and location. Standard treatment for infected bone defects begins with a protocol that includes a series of debridements in conjunction with an extended course of systemic antibiotics. Only after the infection has been eliminated will repair of the defect commence, typically with implantation of autologous bone. To address some of the shortcomings of the standard treatment methods, such as serial procedures, limited grafting material, and the need for a second surgical site for autologous bone, a sequential, dual drug-releasing, moldable, calcium sulfate-based bone graft substitute was developed previously. In the present studies, the effectiveness of the material for treating both the infection with vancomycin and bone defect with simvastatin was evaluated in vivo using a critically sized, infected segmental defect model in rat femurs. Although the infection was not fully eliminated, the local release of vancomycin increased survivorship of infected animals by 464% compared to nontreated controls. Infected animals receiving antimicrobial treatment showed comparable amounts of new bone formation within the defect site when compared to noninfected controls. Incorporating agents capable of disrupting established biofilms into bone graft substitutes may enhance effectiveness in treating a biofilm infection within a bone defect.

Original languageEnglish
Pages (from-to)1878-1886
Number of pages9
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
Volume106
Issue number5
DOIs
StatePublished - Jul 2018

Bibliographical note

Funding Information:
*Present address: Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 Correspondence to: D. Puleo; e-mail: puleo@uky.edu Contract grant sponsor: US Army Medical Research Acquisition Activity; contract grant number: W81XWH-09-1-0461 Contract grant sponsor: NSF IGERT; contract grant number: DGE-0653710

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Keywords

  • bone graft substitute
  • calcium sulfate
  • infection
  • simvastatin
  • vancomycin

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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