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Toxicological profile of nanostructured bone substitute based on hydroxyapatite and poly(Lactide-co-glycolide) after subchronic oral exposure of rats

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2020
2473.pdf (11.22Mb)
Authors
Paraš, S.
Trišić, Dijana
Ajtić, O.M.
Prokić, B.
Drobne, D.
Živković, Slavoljub
Jokanović, Vukoman
Article (Published version)
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Abstract
Novel three-dimensional (3D) nanohydroxyapatite-PLGA scaffolds with high porosity was developed to better mimic mineral component and microstructure of natural bone. To perform a final assessment of this nanomaterial as a potential bone substitute, its toxicological profile was particularly investigated. Therefore, we performed a comet assay on human monocytes for in vitro genotoxicity investigation, and the systemic subchronic toxicity investigation on rats being per oral feed with exactly administrated extract quantities of the nano calcium hydroxyapatite covered with tiny layers of PLGA (ALBO-OS) for 120 days. Histological and stereological parameters of the liver, kidney, and spleen tissue were analyzed. Comet assay revealed low genotoxic potential, while histological analysis and stereological investigation revealed no significant changes in exposed animals when compared to controls, although the volume density of blood sinusoids and connective tissue, as well as numerical density... and number of mitosis were slightly increased. Additionally, despite the significantly increased average number of the Ki67 and slightly increased number of CD68 positive cells in the presence of ALBO-OS, immunoreactive cells proliferation was almost neglected. Blood analyses showed that all of the blood parameters in rats fed with extract nanomaterial are comparable with corresponding parameters of no feed rats, taken as blind probe. This study contributes to the toxicological profiling of ALBO-OS scaffold for potential future application in bone tissue engineering.

Keywords:
Biocompatibility / Bone substitute / Genotoxicity / Hydroxyapatite / Subchronic toxicity
Source:
Nanomaterials, 2020, 10, 5
Publisher:
  • Mdpi Ag
Funding / projects:
  • Chemical and structural designing of nanomaterials for application in medicine and tissue engineering (RS-172026)
  • Slovenian research agency (J1-9162)

DOI: 10.3390/nano10050918

ISSN: 2079-4991

WoS: 000540781800101

Scopus: 2-s2.0-85085069788
[ Google Scholar ]
3
3
URI
https://smile.stomf.bg.ac.rs/handle/123456789/2478
Collections
  • Radovi istraživača
Institution/Community
Stomatološki fakultet
TY  - JOUR
AU  - Paraš, S.
AU  - Trišić, Dijana
AU  - Ajtić, O.M.
AU  - Prokić, B.
AU  - Drobne, D.
AU  - Živković, Slavoljub
AU  - Jokanović, Vukoman
PY  - 2020
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/2478
AB  - Novel three-dimensional (3D) nanohydroxyapatite-PLGA scaffolds with high porosity was developed to better mimic mineral component and microstructure of natural bone. To perform a final assessment of this nanomaterial as a potential bone substitute, its toxicological profile was particularly investigated. Therefore, we performed a comet assay on human monocytes for in vitro genotoxicity investigation, and the systemic subchronic toxicity investigation on rats being per oral feed with exactly administrated extract quantities of the nano calcium hydroxyapatite covered with tiny layers of PLGA (ALBO-OS) for 120 days. Histological and stereological parameters of the liver, kidney, and spleen tissue were analyzed. Comet assay revealed low genotoxic potential, while histological analysis and stereological investigation revealed no significant changes in exposed animals when compared to controls, although the volume density of blood sinusoids and connective tissue, as well as numerical density and number of mitosis were slightly increased. Additionally, despite the significantly increased average number of the Ki67 and slightly increased number of CD68 positive cells in the presence of ALBO-OS, immunoreactive cells proliferation was almost neglected. Blood analyses showed that all of the blood parameters in rats fed with extract nanomaterial are comparable with corresponding parameters of no feed rats, taken as blind probe. This study contributes to the toxicological profiling of ALBO-OS scaffold for potential future application in bone tissue engineering.
PB  - Mdpi Ag
T2  - Nanomaterials
T1  - Toxicological profile of nanostructured bone substitute based on hydroxyapatite and poly(Lactide-co-glycolide) after subchronic oral exposure of rats
VL  - 10
IS  - 5
DO  - 10.3390/nano10050918
ER  - 
@article{
author = "Paraš, S. and Trišić, Dijana and Ajtić, O.M. and Prokić, B. and Drobne, D. and Živković, Slavoljub and Jokanović, Vukoman",
year = "2020",
abstract = "Novel three-dimensional (3D) nanohydroxyapatite-PLGA scaffolds with high porosity was developed to better mimic mineral component and microstructure of natural bone. To perform a final assessment of this nanomaterial as a potential bone substitute, its toxicological profile was particularly investigated. Therefore, we performed a comet assay on human monocytes for in vitro genotoxicity investigation, and the systemic subchronic toxicity investigation on rats being per oral feed with exactly administrated extract quantities of the nano calcium hydroxyapatite covered with tiny layers of PLGA (ALBO-OS) for 120 days. Histological and stereological parameters of the liver, kidney, and spleen tissue were analyzed. Comet assay revealed low genotoxic potential, while histological analysis and stereological investigation revealed no significant changes in exposed animals when compared to controls, although the volume density of blood sinusoids and connective tissue, as well as numerical density and number of mitosis were slightly increased. Additionally, despite the significantly increased average number of the Ki67 and slightly increased number of CD68 positive cells in the presence of ALBO-OS, immunoreactive cells proliferation was almost neglected. Blood analyses showed that all of the blood parameters in rats fed with extract nanomaterial are comparable with corresponding parameters of no feed rats, taken as blind probe. This study contributes to the toxicological profiling of ALBO-OS scaffold for potential future application in bone tissue engineering.",
publisher = "Mdpi Ag",
journal = "Nanomaterials",
title = "Toxicological profile of nanostructured bone substitute based on hydroxyapatite and poly(Lactide-co-glycolide) after subchronic oral exposure of rats",
volume = "10",
number = "5",
doi = "10.3390/nano10050918"
}
Paraš, S., Trišić, D., Ajtić, O.M., Prokić, B., Drobne, D., Živković, S.,& Jokanović, V.. (2020). Toxicological profile of nanostructured bone substitute based on hydroxyapatite and poly(Lactide-co-glycolide) after subchronic oral exposure of rats. in Nanomaterials
Mdpi Ag., 10(5).
https://doi.org/10.3390/nano10050918
Paraš S, Trišić D, Ajtić O, Prokić B, Drobne D, Živković S, Jokanović V. Toxicological profile of nanostructured bone substitute based on hydroxyapatite and poly(Lactide-co-glycolide) after subchronic oral exposure of rats. in Nanomaterials. 2020;10(5).
doi:10.3390/nano10050918 .
Paraš, S., Trišić, Dijana, Ajtić, O.M., Prokić, B., Drobne, D., Živković, Slavoljub, Jokanović, Vukoman, "Toxicological profile of nanostructured bone substitute based on hydroxyapatite and poly(Lactide-co-glycolide) after subchronic oral exposure of rats" in Nanomaterials, 10, no. 5 (2020),
https://doi.org/10.3390/nano10050918 . .

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