TY  - JOUR
AU  - Paraš, Smiljana
AU  - Trišić, Dijana
AU  - Mitrović-Ajtić, Olivera
AU  - Antonijević, Đorđe
AU  - Čolović, Božana M.
AU  - Drobne, Damjana
AU  - Jokanović, Vukoman R.
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9821
AB  - The effects of a new material based on hydroxyapatite and calcium silicates, named ALBO-MPCA, were investigated on the liver, kidney and spleen. The material was administrated orally for 120 days in an in vivo model in Wistar rats, and untreated animals served as a control. Hematological and biochemical blood parameters were analyzed. Qualitative histological analysis of tissues, change in mitotic activity of cells, and histological characteristics was conducted, as well as quantitative stereological analysis of parenchymal cells, blood sinusoids, and connective tissues. Additionally, the protein expressions of Ki67 and CD68 markers were evaluated. Histological analysis revealed no pathological changes after the tested period. It showed the preservation of the architecture of blood sinusoids and epithelial cells and the presence of mitosis. Additionally, the significantly increased number of the Ki67 in the presence of ALBO-MPCA confirmed the proliferative effect of the material noticed by stereological analysis, while immunoreactive CD68 positive cells did not differ between groups. The study showed non-toxicity of the tested material based on the effects on the hematological, biochemical, and observed histological parameters; in addition, it showed evidence of its biocompatibility. These results could be the basis for further steps toward the application of tested materials in endodontics.
T2  - International Journal of Molecular Science
T1  - Biocompatibility study of a new dental cement based on hydroxyapatite and calcium silicates: Focus on liver, kidney, and spleen tissue effects
VL  - 22
IS  - 11
SP  - 5468
DO  - 10.3390/ijms22115468
ER  - 

@article{
author = "Paraš, Smiljana and Trišić, Dijana and Mitrović-Ajtić, Olivera and Antonijević, Đorđe and Čolović, Božana M. and Drobne, Damjana and Jokanović, Vukoman R.",
year = "2021",
abstract = "The effects of a new material based on hydroxyapatite and calcium silicates, named ALBO-MPCA, were investigated on the liver, kidney and spleen. The material was administrated orally for 120 days in an in vivo model in Wistar rats, and untreated animals served as a control. Hematological and biochemical blood parameters were analyzed. Qualitative histological analysis of tissues, change in mitotic activity of cells, and histological characteristics was conducted, as well as quantitative stereological analysis of parenchymal cells, blood sinusoids, and connective tissues. Additionally, the protein expressions of Ki67 and CD68 markers were evaluated. Histological analysis revealed no pathological changes after the tested period. It showed the preservation of the architecture of blood sinusoids and epithelial cells and the presence of mitosis. Additionally, the significantly increased number of the Ki67 in the presence of ALBO-MPCA confirmed the proliferative effect of the material noticed by stereological analysis, while immunoreactive CD68 positive cells did not differ between groups. The study showed non-toxicity of the tested material based on the effects on the hematological, biochemical, and observed histological parameters; in addition, it showed evidence of its biocompatibility. These results could be the basis for further steps toward the application of tested materials in endodontics.",
journal = "International Journal of Molecular Science",
title = "Biocompatibility study of a new dental cement based on hydroxyapatite and calcium silicates: Focus on liver, kidney, and spleen tissue effects",
volume = "22",
number = "11",
pages = "5468",
doi = "10.3390/ijms22115468"
}

Paraš, S., Trišić, D., Mitrović-Ajtić, O., Antonijević, Đ., Čolović, B. M., Drobne, D.,& Jokanović, V. R.. (2021). Biocompatibility study of a new dental cement based on hydroxyapatite and calcium silicates: Focus on liver, kidney, and spleen tissue effects. in International Journal of Molecular Science, 22(11), 5468.
https://doi.org/10.3390/ijms22115468

Paraš S, Trišić D, Mitrović-Ajtić O, Antonijević Đ, Čolović BM, Drobne D, Jokanović VR. Biocompatibility study of a new dental cement based on hydroxyapatite and calcium silicates: Focus on liver, kidney, and spleen tissue effects. in International Journal of Molecular Science. 2021;22(11):5468.
doi:10.3390/ijms22115468 .

Paraš, Smiljana, Trišić, Dijana, Mitrović-Ajtić, Olivera, Antonijević, Đorđe, Čolović, Božana M., Drobne, Damjana, Jokanović, Vukoman R., "Biocompatibility study of a new dental cement based on hydroxyapatite and calcium silicates: Focus on liver, kidney, and spleen tissue effects" in International Journal of Molecular Science, 22, no. 11 (2021):5468,
https://doi.org/10.3390/ijms22115468 . .

TY  - JOUR
AU  - Paraš, Smiljana
AU  - Trišić, Dijana
AU  - Mitrović Ajtić, Olivera
AU  - Prokić, Bogomir
AU  - Drobne, Damjana
AU  - Živković, Slavoljub
AU  - Jokanović, Vukoman R.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9008
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.
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
SP  - 918
DO  - 10.3390/nano10050918
ER  - 

@article{
author = "Paraš, Smiljana and Trišić, Dijana and Mitrović Ajtić, Olivera and Prokić, Bogomir and Drobne, Damjana and Živković, Slavoljub and Jokanović, Vukoman R.",
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.",
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",
pages = "918",
doi = "10.3390/nano10050918"
}

Paraš, S., Trišić, D., Mitrović Ajtić, O., Prokić, B., Drobne, D., Živković, S.,& Jokanović, V. R.. (2020). Toxicological Profile of Nanostructured Bone Substitute Based on Hydroxyapatite and Poly(lactide-co-glycolide) after Subchronic Oral Exposure of Rats. in Nanomaterials, 10(5), 918.
https://doi.org/10.3390/nano10050918

Paraš S, Trišić D, Mitrović Ajtić O, Prokić B, Drobne D, Živković S, Jokanović VR. 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):918.
doi:10.3390/nano10050918 .

Paraš, Smiljana, Trišić, Dijana, Mitrović Ajtić, Olivera, Prokić, Bogomir, Drobne, Damjana, Živković, Slavoljub, Jokanović, Vukoman R., "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):918,
https://doi.org/10.3390/nano10050918 . .

TY  - JOUR
AU  - Paraš, Smiljana
AU  - Janković, Ognjenka
AU  - Trišić, Dijana
AU  - Čolović, Božana M.
AU  - Mitrović‐Ajtić, Olivera
AU  - Dekić, Radoslav
AU  - Soldatović, Ivan A.
AU  - Živković-Sandić, Marija
AU  - Živković, Slavoljub
AU  - Jokanović, Vukoman R.
PY  - 2019
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8557
AB  - Aim: To examine the potential systemic toxicity of nanostructured materials based on calcium silicate and calcium aluminate, for potential application in Dentistry. Methodology: Twenty-four Albino Wistar rats aged 2 months were used as an in vivo animal model for subcutaneous implantation of the investigated materials, placed in polyethylene tubes. Thirty days after implantation, the livers of the rats were analysed and following histological and stereological parameters were evaluated for volume density of hepatocytes and blood sinusoids, number and numerical density of hepatocytes, surface of hepatocytes and their nucleuses, nucleocytoplasmic ratio and mitotic index of hepatocytes. Stereological measurements were achieved using Cavalieri's principle, with grid P2 and unbiased analysis. Additionally, immunohistochemistry studies were performed to further analyse changes in liver tissue. Several haematological and biochemical parameters of blood of experimental animals were also analysed, as well as local tissue reactions around the implants. Statistical analysis was performed using parametric (anova and t-test) and nonparametric tests (Kruskal–Wallis and Mann–Whitney U-test) depending on data distribution. Results: Implanted dental cements led to an increase in stereological and histological parameters in liver tissue compared to control rats. Although the investigated parameters mostly showed significant differences between control and experimental animals, the liver tissue of the experimental animals did not have visible signs of pathological changes. This was supported by the analysis of blood parameters which were not significantly different between control and experimental animals. Also, the subcutaneous tissues had minimal inflammatory reactions. Immunohistochemistry studies revealed that nanostructured materials induced proliferation of hepatocytes, but that the immunological response to the materials was not strong enough to induce proliferation of immunoreactive cells in liver in the observed time period. Conclusions: This study was performed as a contribution to the attestation of the biocompatibility of dental cements based on calcium silicate and calcium aluminate. Although these materials induced several changes in the liver structure, they were not clinically relevant and represent a normal and reversible response of the liver to the presence of biocompatible materials in the body. Blood and immunohistochemistry analyses and local tissue reactions further confirmed that these materials possess good biocompatible potential. © 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd
T2  - International Endodontic Journal
T1  - Influence of nanostructured calcium aluminate and calcium silicate on the liver: histological and unbiased stereological analysis
SP  - 1162
EP  - 1172
DO  - 10.1111/iej.13105
ER  - 

@article{
author = "Paraš, Smiljana and Janković, Ognjenka and Trišić, Dijana and Čolović, Božana M. and Mitrović‐Ajtić, Olivera and Dekić, Radoslav and Soldatović, Ivan A. and Živković-Sandić, Marija and Živković, Slavoljub and Jokanović, Vukoman R.",
year = "2019",
abstract = "Aim: To examine the potential systemic toxicity of nanostructured materials based on calcium silicate and calcium aluminate, for potential application in Dentistry. Methodology: Twenty-four Albino Wistar rats aged 2 months were used as an in vivo animal model for subcutaneous implantation of the investigated materials, placed in polyethylene tubes. Thirty days after implantation, the livers of the rats were analysed and following histological and stereological parameters were evaluated for volume density of hepatocytes and blood sinusoids, number and numerical density of hepatocytes, surface of hepatocytes and their nucleuses, nucleocytoplasmic ratio and mitotic index of hepatocytes. Stereological measurements were achieved using Cavalieri's principle, with grid P2 and unbiased analysis. Additionally, immunohistochemistry studies were performed to further analyse changes in liver tissue. Several haematological and biochemical parameters of blood of experimental animals were also analysed, as well as local tissue reactions around the implants. Statistical analysis was performed using parametric (anova and t-test) and nonparametric tests (Kruskal–Wallis and Mann–Whitney U-test) depending on data distribution. Results: Implanted dental cements led to an increase in stereological and histological parameters in liver tissue compared to control rats. Although the investigated parameters mostly showed significant differences between control and experimental animals, the liver tissue of the experimental animals did not have visible signs of pathological changes. This was supported by the analysis of blood parameters which were not significantly different between control and experimental animals. Also, the subcutaneous tissues had minimal inflammatory reactions. Immunohistochemistry studies revealed that nanostructured materials induced proliferation of hepatocytes, but that the immunological response to the materials was not strong enough to induce proliferation of immunoreactive cells in liver in the observed time period. Conclusions: This study was performed as a contribution to the attestation of the biocompatibility of dental cements based on calcium silicate and calcium aluminate. Although these materials induced several changes in the liver structure, they were not clinically relevant and represent a normal and reversible response of the liver to the presence of biocompatible materials in the body. Blood and immunohistochemistry analyses and local tissue reactions further confirmed that these materials possess good biocompatible potential. © 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd",
journal = "International Endodontic Journal",
title = "Influence of nanostructured calcium aluminate and calcium silicate on the liver: histological and unbiased stereological analysis",
pages = "1162-1172",
doi = "10.1111/iej.13105"
}

Paraš, S., Janković, O., Trišić, D., Čolović, B. M., Mitrović‐Ajtić, O., Dekić, R., Soldatović, I. A., Živković-Sandić, M., Živković, S.,& Jokanović, V. R.. (2019). Influence of nanostructured calcium aluminate and calcium silicate on the liver: histological and unbiased stereological analysis. in International Endodontic Journal, 1162-1172.
https://doi.org/10.1111/iej.13105

Paraš S, Janković O, Trišić D, Čolović BM, Mitrović‐Ajtić O, Dekić R, Soldatović IA, Živković-Sandić M, Živković S, Jokanović VR. Influence of nanostructured calcium aluminate and calcium silicate on the liver: histological and unbiased stereological analysis. in International Endodontic Journal. 2019;:1162-1172.
doi:10.1111/iej.13105 .

Paraš, Smiljana, Janković, Ognjenka, Trišić, Dijana, Čolović, Božana M., Mitrović‐Ajtić, Olivera, Dekić, Radoslav, Soldatović, Ivan A., Živković-Sandić, Marija, Živković, Slavoljub, Jokanović, Vukoman R., "Influence of nanostructured calcium aluminate and calcium silicate on the liver: histological and unbiased stereological analysis" in International Endodontic Journal (2019):1162-1172,
https://doi.org/10.1111/iej.13105 . .