CORR Insights(®): D-amino acid inhibits biofilm but not new bone formation in an ovine model.

Abstract

C omplex musculoskeletal injuries are complicated by infections in as many 30% of traumatized patients [2], depending on the type of injury and the timing of the interventions. Biomaterials often are necessary components to restore function and promote healing in injuries where muscle, nerve, and bone damage present challenges to healing. While biomaterials serve critical functions in repairing defects, they also increase the risk of infection. This is in part due to the promotion of biofilm formation on the surface of implants, and in particular, the presence of persister cells (dormant cells that survive exposure to antimicrobials) within biofilm. Biofilm microorganisms and persister cells have altered metabolic function that make them resistant to traditional antibiotic therapy and require antimicrobial concentrations several orders of magnitude higher for complete eradication than those necessary for killing planktonic counterparts [9]. Basic science studies of biofilm and persister-cell biology have led to the discovery of a number of molecules that specifically target these phenotypes. D-amino acids (D-AAs), cis 2decenoic acid, and farnesol are among these recently discovered biofilm inhibitors that have been shown to prevent biofilm formation, disperse existing biofilm, and revert persister cells to a more active and antimicrobial-susceptible state [4, 7, 8]. While in vitro results using D-AAs are encouraging, clinical use of these biofilm inhibitors remains investigational. Dose considerations and compatibility with bone and soft tissue must be established for safety. Since systemic delivery of D-AAs and other biofilm inhibitors may be ineffective, local delivery carriers for D-AAs are an advantageous strategy for clinical use.