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

Paraš, Smiljana (author), Trišić, Dijana (author), Mitrović Ajtić, Olivera (author), Prokić, Bogomir (author), Drobne, Damjana (author), Živković, Slavoljub (author), Jokanović, Vukoman (author)

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.

• Language: English
• Keywords: hydroxyapatite, bone substitute, genotoxicity, subchronic toxicity, biocompatibility
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 21 str.
• Numbering: Vol. 10, iss. 5, art. 918
• PID: 20.500.12556/RUL-133739
• UDC: 577
• ISSN on article: 2079-4991
• DOI: 10.3390/nano10050918
• COBISS.SI-ID: 15090691
• Publication date in RUL: 13.12.2021

Record is a part of a journal

• Title: Nanomaterials
• Shortened title: Nanomaterials
• Publisher: MDPI AG
• ISSN: 2079-4991
• COBISS.SI-ID: 523286297

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 09.05.2020

Secondary language

• Language: Slovenian
• Keywords: biokemija, genotoksičnost, kostni nadomestki, nanomateriali

Projects

• Funder: MESTD - Ministry of Education, Science and Technological Development of Republic of Serbia
• Funding programme: Basic Research (BR or ON)
• Project number: 172026
• Name: Chemical and structural designing of nanomaterials for application in medicine and tissue engineering

• Funder: ARRS - Slovenian Research Agency
• Project number: J1-9162
• Name: Neurotoksičnost ali neuroprotektivnost nanomaterialov: vpliv biokorone