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

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.