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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 831-840 |
| Number of pages | 10 |
| Journal | Materials Science and Engineering C |
| Volume | 69 |
| DOIs | |
| State | Published - Dec 1 2016 |
| Externally published | Yes |
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Keywords
- 3D cell culture
- Bone implants
- Local drug delivery
- Parathyroid hormone
- TiO nanotubes
- Titanium
ASJC Scopus subject areas
- Materials Science(all)
- Condensed Matter Physics
- Mechanics of Materials
- Mechanical Engineering
Cite this
Drug-releasing nano-engineered titanium implants : therapeutic efficacy in 3D cell culture model, controlled release and stability. / Gulati, Karan; Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M.; Atkins, Gerald J.; Losic, Dusan.
In: Materials Science and Engineering C, Vol. 69, 01.12.2016, p. 831-840.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Drug-releasing nano-engineered titanium implants
T2 - therapeutic efficacy in 3D cell culture model, controlled release and stability
AU - Gulati, Karan
AU - Kogawa, Masakazu
AU - Prideaux, Matthew
AU - Findlay, David M.
AU - Atkins, Gerald J.
AU - Losic, Dusan
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - 3D cell culture
KW - Bone implants
KW - Local drug delivery
KW - Parathyroid hormone
KW - TiO nanotubes
KW - Titanium
UR - http://www.scopus.com/inward/record.url?scp=84979788613&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979788613&partnerID=8YFLogxK
U2 - 10.1016/j.msec.2016.07.047
DO - 10.1016/j.msec.2016.07.047
M3 - Article
C2 - 27612777
AN - SCOPUS:84979788613
VL - 69
SP - 831
EP - 840
JO - Materials Science and Engineering C
JF - Materials Science and Engineering C
SN - 0928-4931
ER -