Drug diffusion, integration, and stability of nanoengineered drug-releasing implants in bone ex-vivo.
To treat skeletal conditions such as bone infections, osteoporotic fractures, and osteosarcoma, it would be ideal to introduce drugs directly to the affected site. Localized drug delivery from the bone implants is a promising alternative to systemic drug administration. In this study we investigated electrochemically nanoengineered Ti wire implants with titania nanotubes (TNTs), as minimally invasive drug-releasing implants for the delivery of drugs directly into the bone tissue. Since trabecular bone in vivo contains a highly interconnected bone marrow, we sought to determine the influence of marrow on drug release and diffusion. Electrochemical anodization of Ti wires (length 10 mm) was performed to create an oxide layer with TNTs on the surface, followed by loading with a fluorescent model drug, Rhodamine B (RhB). Cores of bovine trabecular bone were generated from the sternum of a young steer, and were processed to have an intact bone marrow, or the marrow was removed. RhB-loaded TNTs/Ti wires were inserted into the bone cores, which were then cultured ex vivo using the ZetOS™ bioreactor system to maintain bone viability. Release and diffusion of RhB inside the bone was monitored using fluorescence imaging and different patterns of drug transport in the presence or absence of marrow were observed. Scanning electron microscopy of the implants after retrieval from bone cores confirmed survival of the TNTs structures. Histological investigation showed the presence of bone cells adherent on the implants. This study shows a potential of Ti drug-releasing implants based on TNTs technology towards localized bone therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 714-725, 2016.
School of Chemical Engineering, University of Adelaide, SA 5005, Australia.
Shafiur
S
Rahman
School of Chemical Engineering, University of Adelaide, SA 5005, Australia.
Karan
K
Gulati
Discipline of Orthopaedics and Trauma, University of Adelaide, SA 5005, Australia.
Masakazu
M
Kogawa
Discipline of Orthopaedics and Trauma, University of Adelaide, SA 5005, Australia.
Gerald J
GJ
Atkins
Australian Institute for Musculoskeletal Science, University of Melbourne, VIC 3021, Australia.
Peter
P
Pivonka
Discipline of Orthopaedics and Trauma, University of Adelaide, SA 5005, Australia.
David M
DM
Findlay
School of Chemical Engineering, University of Adelaide, SA 5005, Australia.
Dusan
D
Losic
D000818:Animals; D000071556:Cancellous Bone / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D060833:Cellular Microenvironment / Q000187:drug effects; D004058:Diffusion; D004343:Drug Implants; D065546:Drug Liberation; D036103:Nanotechnology / Q000379:methods*; D043942:Nanotubes / Q000737:chemistry / Q000648:ultrastructure; D012235:Rhodamines / Q000494:pharmacology*; D014025:Titanium / Q000737:chemistry
D004343:Drug Implants; D012235:Rhodamines; C009495:titanium dioxide; D014025:Titanium; C029773:rhodamine B
bone therapy; drug diffusion; drug-releasing implants; local drug delivery; titania nanotubes