Effects of local delivery of d-amino acids from biofilm-dispersive scaffolds on infection in contaminated rat segmental defects

Carlos J. Sanchez, Edna M. Prieto, Chad A. Krueger, Katarzyna J. Zienkiewicz, Desiree R. Romano, Catherine L. Ward, Kevin S. Akers, Scott A. Guelcher, Joseph C. Wenke

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Infectious complications of open fractures continue to be a significant factor contributing to non-osseous union and extremity amputation. The persistence of bacteria within biofilms despite meticulous debridement and antibiotic therapy is believed to be a major cause of chronic infection. Considering the difficulties in treating biofilm-associated infections, the use of biofilm dispersal agents as a therapeutic strategy for the prevention of biofilm-associated infections has gained considerable interest. In this study, we investigated whether local delivery of d-Amino Acids (d-AAs), a biofilm dispersal agent, protects scaffolds from contamination and reduces microbial burden within contaminated rat segmental defects invivo. Invitro testing on biofilms of clinical isolates of Staphylococcus aureus demonstrated that d-Met, d-Phe, d-Pro, and d-Trp were highly effective at dispersing and preventing biofilm formation individually, and the effect was enhanced for an equimolar mixture of d-AAs. Incorporation of d-AAs into polyurethane scaffolds as a mixture (1:1:1 d-Met:. d-Pro:. d-Trp) significantly reduced bacterial contamination on the scaffold surface invitro and within bone when implanted into contaminated femoral segmental defects. Our results underscore the potential of local delivery of d-AAs for reducing bacterial contamination by targeting bacteria within biofilms, which may represent a treatment strategy for improving healing outcomes associated with open fractures.

Original languageEnglish (US)
Pages (from-to)7533-7543
Number of pages11
JournalBiomaterials
Volume34
Issue number30
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Biofilm
  • Dispersal agent
  • Open fracture
  • Osteomyelitis
  • Scaffold
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Mechanics of Materials
  • Ceramics and Composites
  • Bioengineering
  • Biophysics
  • Biomaterials

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