title: Antibiotic modification of native grafts: improving upon nature's scaffolds.
abstract: Infection associated with inert implants is complicated by bacterial biofilm formation that renders the infection antibiotic insensitive. The goal of this investigation was to synthesize and characterize a vancomycin (VAN)-modified bone allograft that could render the tissue inhospitable to bacterial colonization and the establishment of infection. We found that the numbers of primary amines, which could serve as anchors for chemical synthesis, increased with limited demineralization. Using these amines, we coupled two linkers and VAN to bone using Fmoc chemistry. By immunohistochemistry, VAN was abundant on the surface of the allograft; based on elution and measurement of bound antibody, this coupling yielded at least approximately 26 ng VAN/mg bone. The coupled VAN appeared to be permanently bound to the allograft, as it showed no elution in a disk diffusion assay, and, importantly, resisted colonization by Staphylococcus aureus challenges. We suggest that this chimeric construct represents a new generation of antibiotic-modified allografts that provide antibacterial properties.
authors.affiliation: Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Ketonis
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Adams
authors.forename: Stephanie
authors.initials: S
authors.lastname: Barr
authors.forename: Amiethab
authors.initials: A
authors.lastname: Aiyer
authors.forename: Irving M
authors.initials: IM
authors.lastname: Shapiro
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
authors.forename: Noreen J
authors.initials: NJ
authors.lastname: Hickok
mesh_terms: D000588:Amines / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D013054:Spectrophotometry, Atomic; D013211:Staphylococcus aureus / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D014184:Transplantation, Homologous / Q000379:methods*; D014640:Vancomycin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000588:Amines; D000900:Anti-Bacterial Agents; D014640:Vancomycin