Toxicological Profile of Nanostructured Bone Substitute Based on Hydroxyapatite and Poly(lactide-co-glycolide) after Subchronic Oral Exposure of Rats

Nanomaterials

Damjana Drobne¹  Olivera Mitrović Ajtić²  Vukoman Jokanović³  Dijana Trišić⁴  Slavoljub Živković⁴  Smiljana Paraš⁵  Bogomir Prokić⁶ 

[1] Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia;Department for Molecular Oncology, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia;Department of Atomics Physics, Vinča Institute of Nuclear Sciences, University of Belgrade, 11000 Belgrade, Serbia;Faculty of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia;Faculty of Science and Mathematics, University of Banja Luka, 78000 Banja Luka, Republic of Srpska, Bosnia and Herzegovina;School of Veterinary Medicine, University of Belgrade, 11000 Belgrade, Serbia;

关键词: hydroxyapatite;    bone substitute;    genotoxicity;    subchronic toxicity;    biocompatibility;   

DOI  :  10.3390/nano10050918

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown