1. Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability.
- Author
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Gulati K, Kogawa M, Prideaux M, Findlay DM, Atkins GJ, and Losic D
- Subjects
- Animals, Cancellous Bone drug effects, Cancellous Bone ultrastructure, Cattle, Cell Communication drug effects, Cell Line, Tumor, Cell Movement drug effects, Cell Shape drug effects, Delayed-Action Preparations, Drug Stability, Gene Expression Regulation drug effects, Humans, Implants, Experimental, Nanotubes ultrastructure, Osteoblasts cytology, Osteoblasts drug effects, Osteoblasts metabolism, Osteoblasts ultrastructure, Cell Culture Techniques methods, Drug Liberation, Indomethacin pharmacology, Nanotechnology methods, Nanotubes chemistry, Parathyroid Hormone pharmacology, Prostheses and Implants, Titanium chemistry
- Abstract
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., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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