title: Chitosan coatings deliver antimicrobials from titanium implants: a preliminary study.
abstract: OBJECTIVE
  Chitosan was investigated as a coating for local delivery of antimicrobials for prevention of acute implant infection. The objectives of this study were to (1) measure the release of 2 antimicrobials from chitosan coatings, (2) determine efficacy of eluted antimicrobials against bacteria, in vitro, and (3) evaluate toxicity of eluted drugs to host cells/tissues.
  
  
  METHODS
  Chitosan coatings (80.7% deacetylated, 108 kDa) containing 20% tetracycline or 0.02% chlorhexidine digluconate were bonded to titanium via silane reactions. After elution in culture medium for 7 days, eluates were tested against model pathogens Actinobacillus actinomycetemcomitans and Staphylococcus epidermidis in turbidity tests and in 24-hour cytotoxicity tests using human osteoblasts and fibroblasts. Finally, antibiotic-loaded chitosan-coated titanium pins were implanted for 7 days in muscle of Sprague-Dawley rats to evaluate the initial tissue response.
  
  
  RESULTS
  Coatings released 89% of tetracycline in 7 days and 100% chlorhexidine in 2 days. Released tetracycline inhibited growth (95%-99.9%) of pathogens for up to 7 days with no cytotoxicity to human cells. Released chlorhexidine was active against pathogens for 1 to 2 days (56%-99.5% inhibition) but was toxic to cells on the first day of elution. Typical acute inflammatory response was observed to antimicrobial-loaded chitosan coatings similar to unloaded coatings.
  
  
  CONCLUSIONS
  These preliminary data support the hypothesis that chitosan coatings have the potential to locally deliver antimicrobials to inhibit bacteria without being toxic to host cells/tissues and warrant additional studies to evaluate the ability of the coatings to prevent/resist infection and promote osseointegration.
authors.affiliation: Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA. pnorowsk@memphis.edu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Norowski
authors.forename: Harry S
authors.initials: HS
authors.lastname: Courtney
authors.forename: Jegdish
authors.initials: J
authors.lastname: Babu
authors.forename: Warren O
authors.initials: WO
authors.lastname: Haggard
authors.forename: Joel D
authors.initials: JD
authors.lastname: Bumgardner
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000633:toxicity; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D002710:Chlorhexidine / Q000008:administration & dosage / Q000633:toxicity; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D017077:Culture Media, Conditioned; D015921:Dental Implants; D003764:Dental Materials / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007249:Inflammation; D008422:Materials Testing; D018482:Muscle, Skeletal / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013499:Surface Properties; D013752:Tetracycline / Q000008:administration & dosage / Q000633:toxicity; D014025:Titanium / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D000891:Anti-Infective Agents, Local; D020099:Coated Materials, Biocompatible; D017077:Culture Media, Conditioned; D015921:Dental Implants; D003764:Dental Materials; D004337:Drug Carriers; D048271:Chitosan; D014025:Titanium; D013752:Tetracycline; D002710:Chlorhexidine