Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability.
There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements.
School of Chemical Engineering, The University of Adelaide, SA 5005, Australia.
Karan
K
Gulati
Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005, Australia.
Masakazu
M
Kogawa
Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005, Australia.
Matthew
M
Prideaux
Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005, Australia.
David M
DM
Findlay
Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005, Australia. Electronic address: gerald.atkins@adelaide.edu.au.
Gerald J
GJ
Atkins
School of Chemical Engineering, The University of Adelaide, SA 5005, Australia. Electronic address: dusan.losic@adelaide.edu.au.
Dusan
D
Losic
D000818:Animals; D000071556:Cancellous Bone / Q000187:drug effects / Q000648:ultrastructure; D002417:Cattle; D002450:Cell Communication / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003692:Delayed-Action Preparations; D065546:Drug Liberation; D004355:Drug Stability; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020007:Implants, Experimental; D007213:Indomethacin / Q000494:pharmacology*; D036103:Nanotechnology / Q000379:methods*; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010281:Parathyroid Hormone / Q000494:pharmacology*; D019736:Prostheses and Implants; D014025:Titanium / Q000737:chemistry*
D003692:Delayed-Action Preparations; D010281:Parathyroid Hormone; D014025:Titanium; D007213:Indomethacin
3D cell culture; Bone implants; Local drug delivery; Parathyroid hormone; TiO(2) nanotubes; Titanium