title: Hydrophobic polycationic coatings that inhibit biofilms and support bone healing during infection.
abstract: Adhesion of microorganisms to biomaterials with subsequent formation of biofilms on such foreign bodies as orthopedic trauma hardware is a critical factor in implant-associated infections; once a biofilm has been established, its microorganisms become recalcitrant to the host's immune surveillance and markedly resistant to drugs. We have previously reported that painting with the hydrophobic polycation N,N-dodecyl,methyl-PEI (PEI = polyethylenimine) renders solid surfaces bactericidal in vitro. Herein we observe that N,N-dodecyl,methyl-PEI-derivatized titanium and stainless steel surfaces resist biofilm formation by Staphylococcus aureus compared to the untreated ones. Using imaging, microbiology-, histopathology-, and scanning electron microscopy (SEM) experiments in a clinically relevant large-animal (sheep) trauma model, we subsequently demonstrate in vivo that orthopedic fracture hardware painted with N,N-dodecyl,methyl-PEI not only prevents implant colonization with biofilm but also promotes bone healing. Functionalizing orthopedic hardware with hydrophobic polycations thus holds promise in supporting bone healing in the presence of infection in veterinary and human orthopedic patients.
authors.affiliation: Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA 19348, USA. tpschaer@vet.upenn.edu
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Schaer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Stewart
authors.forename: Bryan B
authors.initials: BB
authors.lastname: Hsu
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Klibanov
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D015169:Colony Count, Microbial; D017102:Fracture Healing / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D010027:Osteotomy; D011073:Polyamines / Q000494:pharmacology*; D000071228:Polyelectrolytes; D011094:Polyethyleneimine / Q000494:pharmacology; D011859:Radiography; D012756:Sheep; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D020099:Coated Materials, Biocompatible; D011073:Polyamines; D000071228:Polyelectrolytes; D011094:Polyethyleneimine