title: A biodegradable gentamicin-hydroxyapatite-coating for infection prophylaxis in cementless hip prostheses.
abstract: A degradable, poly (lactic-co-glycolic acid) (PLGA), gentamicin-loaded prophylactic coating for hydroxyapatite (HA)-coated cementless hip prostheses is developed with similar antibacterial efficacy as offered by gentamicin-loaded cements for fixing traditional, cemented prostheses in bone. We describe the development pathway, from in vitro investigation of antibiotic release and antibacterial properties of this PLGA-gentamicin-HA-coating in different in vitro models to an evaluation of its efficacy in preventing implant-related infection in rabbits. Bone in-growth in the absence and presence of the coating was investigated in a canine model. The PLGA-gentamicin-HA-coating showed high-burst release, with antibacterial efficacy in agar-assays completely disappearing after 4 days, minimising risk of inducing antibiotic resistance. Gentamicin-sensitive and gentamicin-resistant staphylococci were killed by the antibiotic-loaded coating, in a simulated prosthesis-related interfacial gap. PLGA-gentamicin-HA-coatings prevented growth of bioluminescent staphylococci around a miniature-stem mounted in bacterially contaminated agar, as observed using bio-optical imaging. PLGA-gentamicin-HA-coated pins inserted in bacterially contaminated medullary canals in rabbits caused a statistically significant reduction in infection rates compared to HA-coated pins without gentamicin. Bone ingrowth to PLGA-gentamicin-HA-coated pins, in condylar defects of Beagle dogs was not impaired by the presence of the degradable, gentamicin-loaded coating. In conclusion, the PLGA-gentamicin-HA-coating constitutes an effective strategy for infection prophylaxis in cementless prostheses.
authors.affiliation: Department of Biomedical Engineering (FB40), W.J. Kolff Institute, University of Groningen and University Medical Center Groningen, PO Box 196, 9700 AD Groningen, The Netherlands.d.neut@umcg.nl.
authors.forename: D
authors.initials: D
authors.lastname: Neut
authors.forename: R J
authors.initials: RJ
authors.lastname: Dijkstra
authors.forename: J I
authors.initials: JI
authors.lastname: Thompson
authors.forename: C
authors.initials: C
authors.lastname: Kavanagh
authors.forename: H C
authors.initials: HC
authors.lastname: van der Mei
authors.forename: H J
authors.initials: HJ
authors.lastname: Busscher
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001843:Bone Cements; D001858:Bone Nails; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D017886:Durapatite / Q000737:chemistry*; D005260:Female; D005269:Femur / Q000601:surgery; D005839:Gentamicins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006622:Hip Prosthesis; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D016348:Osseointegration / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016459:Prosthesis-Related Infections / Q000382:microbiology / Q000517:prevention & control*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001843:Bone Cements; D020099:Coated Materials, Biocompatible; D005839:Gentamicins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017886:Durapatite