title: Effects of local delivery of D-amino acids from biofilm-dispersive scaffolds on infection in contaminated rat segmental defects.
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 in vivo. In vitro 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 in vitro 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.
authors.affiliation: United States Army Institute of Surgical Research, Extremity Trauma and Regenerative Medicine Task Area, Fort Sam Houston, San Antonio, TX, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Sanchez
authors.forename: Edna M
authors.initials: EM
authors.lastname: Prieto
authors.forename: Chad A
authors.initials: CA
authors.lastname: Krueger
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Zienkiewicz
authors.forename: Desiree R
authors.initials: DR
authors.lastname: Romano
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Ward
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Akers
authors.forename: Scott A
authors.initials: SA
authors.lastname: Guelcher
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D018441:Biofilms / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005269:Femur / Q000187:drug effects / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D011140:Polyurethanes / Q000494:pharmacology; D051381:Rats; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology* / Q000648:ultrastructure; D054457:Tissue Scaffolds / Q000382:microbiology*
chemical_list: D000596:Amino Acids; D011140:Polyurethanes
keywords: Biofilm; Dispersal agent; Open fracture; Osteomyelitis; Scaffold; Staphylococcus aureus