title: Biocompatible polymer coating of titania nanotube arrays for improved drug elution and osteoblast adhesion.
abstract: Bacterial infection, extensive inflammation and poor osseointegration have been identified as the major reasons for [early] orthopaedic implant failures based on titanium. Creating implants with drug-eluting properties to locally deliver drugs is an appealing way to address some of these problems. To improve properties of titanium for orthopaedic applications, this study explored the modification of titanium surfaces with titaniananotube (TNT) arrays, and approach that combines drug delivery into bone and potentially improved bone integration. A titania layer with an array of nanotube structures (∼120 nm in diameter and 50 μm in length) was synthesized on titanium surfaces by electrochemical anodization and loaded with the water-insoluble anti-inflammatory drug indomethacin. A simple dip-coating process of polymer modification formed thin biocompatible polymer films over the drug-loaded TNTs to create TNTs with predictable drug release characteristics. Two biodegradable and antibacterial polymers, chitosan and poly(lactic-co-glycolic acid), were tested for their ability to extend the drug release time of TNTs and produce favourable bone cell adhesion properties. Dependent on polymer thickness, a significant improvement in the drug release characteristics was demonstrated, with reduced burst release (from 77% to >20%) and extended overall release from 4 days to more than 30 days. Excellent osteoblast adhesion and cell proliferation on polymer-coated TNTs compared with uncoated TNTs were also observed. These results suggest that polymer-modified implants with a TNT layer are capable of delivering a drug to a bone site over an extended period and with predictable kinetics. In addition, favourable bone cell adhesion suggests that such an implant would have good biocompatibility. The described approach is broadly applicable to a wide range of drugs and implants currently used in orthopaedic practice.
authors.affiliation: Ian Wark Research Institute, University of South Australia, Adelaide, SA, Australia.
authors.forename: Karan
authors.initials: K
authors.lastname: Gulati
authors.forename: Saminathan
authors.initials: S
authors.lastname: Ramakrishnan
authors.forename: Moom Sinn
authors.initials: MS
authors.lastname: Aw
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Atkins
authors.forename: David M
authors.initials: DM
authors.lastname: Findlay
authors.forename: Dusan
authors.initials: D
authors.lastname: Losic
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D007213:Indomethacin / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D043942:Nanotubes / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; C009495:titanium dioxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D014025:Titanium; D007213:Indomethacin