TY  - JOUR
AU  - Radonjić, Mia
AU  - Petrović, Jelena
AU  - Milivojević, Milena
AU  - Stevanović, Milena
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5261
AB  - A multidisciplinary approach based on experiments and mathematical modeling was used in biomimetic system development for three-dimensional (3D) cultures of cancer cells. Specifically, two cancer cell lines, human embryonic teratocarcinoma NT2/D1 and rat glioma C6, were immobilized in alginate microbeads and microfibers, respectively, and cultured under static and flow conditions in perfusion bioreactors. At the same time, chemical engineering methods were applied to explain the obtained results. The superficial medium velocity of 80 μm s-1 induced lower viability of NT2/D1 cells in superficial microbead zones, implying adverse effects of fluid shear stresses estimated as ∼67 mPa. On the contrary, similar velocity (100 μm s-1) enhanced the proliferation of C6 glioma cells within microfibers compared to static controls. An additional study of silver release from nanocomposite Ag/honey/alginate microfibers under perfusion indicated that the medium partially flows through the hydrogel (interstitial velocity of ∼10 nm s-1). Thus, a diffusion-advection-reaction model described the mass transport to immobilized cells within microfibers. Substances with diffusion coefficients of ∼10-9-10-11 m2 s-1 are sufficiently supplied by diffusion only, while those with significantly lower diffusivities (∼10-19 m2 s-1) require additional convective transport. The present study demonstrates the selection and contribution of chemical engineering methods in tumor model system development.
PB  - National Library of Serbia
T2  - Chemical Industry and Chemical Engineering Quarterly
T2  - Chemical Industry and Chemical Engineering Quarterly
T1  - Chemical engineering methods in analyses of 3D cancer cell cultures: Hydrodinamic and mass transport considerations
EP  - 223
IS  - 3
SP  - 211
VL  - 28
DO  - 10.2298/CICEQ210607033R
ER  - 

@article{
author = "Radonjić, Mia and Petrović, Jelena and Milivojević, Milena and Stevanović, Milena and Stojkovska, Jasmina and Obradović, Bojana",
year = "2022",
abstract = "A multidisciplinary approach based on experiments and mathematical modeling was used in biomimetic system development for three-dimensional (3D) cultures of cancer cells. Specifically, two cancer cell lines, human embryonic teratocarcinoma NT2/D1 and rat glioma C6, were immobilized in alginate microbeads and microfibers, respectively, and cultured under static and flow conditions in perfusion bioreactors. At the same time, chemical engineering methods were applied to explain the obtained results. The superficial medium velocity of 80 μm s-1 induced lower viability of NT2/D1 cells in superficial microbead zones, implying adverse effects of fluid shear stresses estimated as ∼67 mPa. On the contrary, similar velocity (100 μm s-1) enhanced the proliferation of C6 glioma cells within microfibers compared to static controls. An additional study of silver release from nanocomposite Ag/honey/alginate microfibers under perfusion indicated that the medium partially flows through the hydrogel (interstitial velocity of ∼10 nm s-1). Thus, a diffusion-advection-reaction model described the mass transport to immobilized cells within microfibers. Substances with diffusion coefficients of ∼10-9-10-11 m2 s-1 are sufficiently supplied by diffusion only, while those with significantly lower diffusivities (∼10-19 m2 s-1) require additional convective transport. The present study demonstrates the selection and contribution of chemical engineering methods in tumor model system development.",
publisher = "National Library of Serbia",
journal = "Chemical Industry and Chemical Engineering Quarterly, Chemical Industry and Chemical Engineering Quarterly",
title = "Chemical engineering methods in analyses of 3D cancer cell cultures: Hydrodinamic and mass transport considerations",
pages = "223-211",
number = "3",
volume = "28",
doi = "10.2298/CICEQ210607033R"
}

Radonjić, M., Petrović, J., Milivojević, M., Stevanović, M., Stojkovska, J.,& Obradović, B.. (2022). Chemical engineering methods in analyses of 3D cancer cell cultures: Hydrodinamic and mass transport considerations. in Chemical Industry and Chemical Engineering Quarterly
National Library of Serbia., 28(3), 211-223.
https://doi.org/10.2298/CICEQ210607033R

Radonjić M, Petrović J, Milivojević M, Stevanović M, Stojkovska J, Obradović B. Chemical engineering methods in analyses of 3D cancer cell cultures: Hydrodinamic and mass transport considerations. in Chemical Industry and Chemical Engineering Quarterly. 2022;28(3):211-223.
doi:10.2298/CICEQ210607033R .

Radonjić, Mia, Petrović, Jelena, Milivojević, Milena, Stevanović, Milena, Stojkovska, Jasmina, Obradović, Bojana, "Chemical engineering methods in analyses of 3D cancer cell cultures: Hydrodinamic and mass transport considerations" in Chemical Industry and Chemical Engineering Quarterly, 28, no. 3 (2022):211-223,
https://doi.org/10.2298/CICEQ210607033R . .

TY  - CONF
AU  - Banićević, Ivana
AU  - Menshikh, Ksenia
AU  - Radonjić, Mia
AU  - Petrović, Jelena
AU  - Janković, Radmila
AU  - Milivojević, Milena
AU  - Stevanović, Milena
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6350
PB  - Institute of Technical Sciences of SASA
C3  - Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts
T1  - Cellular self-assembly in a 3D osteosarcoma culture model based on alginate scaffolds and perfusion bioreactor
SP  - 9
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6350
ER  - 

@conference{
author = "Banićević, Ivana and Menshikh, Ksenia and Radonjić, Mia and Petrović, Jelena and Janković, Radmila and Milivojević, Milena and Stevanović, Milena and Stojkovska, Jasmina and Obradović, Bojana",
year = "2022",
publisher = "Institute of Technical Sciences of SASA",
journal = "Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts",
title = "Cellular self-assembly in a 3D osteosarcoma culture model based on alginate scaffolds and perfusion bioreactor",
pages = "9",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6350"
}

Banićević, I., Menshikh, K., Radonjić, M., Petrović, J., Janković, R., Milivojević, M., Stevanović, M., Stojkovska, J.,& Obradović, B.. (2022). Cellular self-assembly in a 3D osteosarcoma culture model based on alginate scaffolds and perfusion bioreactor. in Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts
Institute of Technical Sciences of SASA., 9.
https://hdl.handle.net/21.15107/rcub_technorep_6350

Banićević I, Menshikh K, Radonjić M, Petrović J, Janković R, Milivojević M, Stevanović M, Stojkovska J, Obradović B. Cellular self-assembly in a 3D osteosarcoma culture model based on alginate scaffolds and perfusion bioreactor. in Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts. 2022;:9.
https://hdl.handle.net/21.15107/rcub_technorep_6350 .

Banićević, Ivana, Menshikh, Ksenia, Radonjić, Mia, Petrović, Jelena, Janković, Radmila, Milivojević, Milena, Stevanović, Milena, Stojkovska, Jasmina, Obradović, Bojana, "Cellular self-assembly in a 3D osteosarcoma culture model based on alginate scaffolds and perfusion bioreactor" in Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts (2022):9,
https://hdl.handle.net/21.15107/rcub_technorep_6350 .

TY  - CONF
AU  - Petrović, Jelena
AU  - Radonjić, Mia
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5033
AB  - Glioblastoma is the most common and aggressive malignant brain tumor in adults. Existing
treatment choices that include surgery, radiation and chemotherapy are not successful in
long-term survival, while development of new anticancer drugs is being held back by the
lack of adequate model systems for anticancer drug testing. Namely, in traditionally used
two-dimensional (2D) monolayer cancer cell cultures the native cell morphology, polarity
and interactions between both cells and cells and extracellular components are either
changed or absent, while studies on animals often produce misleading results due to
interspecies differences. Hence, there is a pressing need for new glioblastoma model systems
that provide more in vivo-like environment for investigation and development of new
anticancer drugs. The aim of this work was to develop a biomimetic 3D environment for
cultivation of glioblastoma cells based on alginate microfibers as cell carriers and perfusion
bioreactors. Previous studies have shown that static cultures of cervical cancer cells SiHa
immobilized in alginate microfibers may be diffusion limited while perfusion, which
enhanced mass transport, has induced negative effects on human embryonic teratocarcinoma
cells NTERA-2 in superficial zones of alginate microbeads by hydrodynamic shear stresses.
Thus, in the present study, the specific focus was on optimization of cell concentration
within microfibers and regimes of cultivation to achieve beneficial effects of fluid flow in
perfusion bioreactors. A series of experiments were conducted in which the concentration of
rat glioma cells C6 was varied between 2 and 8 × 10
6
cell cm
-3
at several flowrates and
regimens of static and perfusion culture periods. Mixed results were obtained implying that
efficient mass transport has a higher effect in microfiber cultures at lower cell concentrations
(i.e. ~2 × 10
6
cell cm
-3
). In specific, medium flow at the superficial velocity of 100 µm s
-1
induced considerable cell proliferation as compared to control static cultures, which
maintained the initial cell numbers. Mathematical modelling indicated that the convective
transport of substances with low diffusion coefficients (~10
-19 m
2
s
-1
) may have induced the
observed positive effects. Still, exact relations of cultivation conditions and cell responses in
terms of viability, proliferation and metabolic activity should be further investigated.
PB  - Institute of Technical Sciences of SASA
C3  - Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts
T1  - Optimization of Bioreactor Cultures of Glioblastoma Cells Immobilized in Alginate Microfibers
SP  - 8
VL  - 18
UR  - https://hdl.handle.net/21.15107/rcub_technorep_5033
ER  - 

@conference{
author = "Petrović, Jelena and Radonjić, Mia and Stojkovska, Jasmina and Obradović, Bojana",
year = "2021",
abstract = "Glioblastoma is the most common and aggressive malignant brain tumor in adults. Existing
treatment choices that include surgery, radiation and chemotherapy are not successful in
long-term survival, while development of new anticancer drugs is being held back by the
lack of adequate model systems for anticancer drug testing. Namely, in traditionally used
two-dimensional (2D) monolayer cancer cell cultures the native cell morphology, polarity
and interactions between both cells and cells and extracellular components are either
changed or absent, while studies on animals often produce misleading results due to
interspecies differences. Hence, there is a pressing need for new glioblastoma model systems
that provide more in vivo-like environment for investigation and development of new
anticancer drugs. The aim of this work was to develop a biomimetic 3D environment for
cultivation of glioblastoma cells based on alginate microfibers as cell carriers and perfusion
bioreactors. Previous studies have shown that static cultures of cervical cancer cells SiHa
immobilized in alginate microfibers may be diffusion limited while perfusion, which
enhanced mass transport, has induced negative effects on human embryonic teratocarcinoma
cells NTERA-2 in superficial zones of alginate microbeads by hydrodynamic shear stresses.
Thus, in the present study, the specific focus was on optimization of cell concentration
within microfibers and regimes of cultivation to achieve beneficial effects of fluid flow in
perfusion bioreactors. A series of experiments were conducted in which the concentration of
rat glioma cells C6 was varied between 2 and 8 × 10
6
cell cm
-3
at several flowrates and
regimens of static and perfusion culture periods. Mixed results were obtained implying that
efficient mass transport has a higher effect in microfiber cultures at lower cell concentrations
(i.e. ~2 × 10
6
cell cm
-3
). In specific, medium flow at the superficial velocity of 100 µm s
-1
induced considerable cell proliferation as compared to control static cultures, which
maintained the initial cell numbers. Mathematical modelling indicated that the convective
transport of substances with low diffusion coefficients (~10
-19 m
2
s
-1
) may have induced the
observed positive effects. Still, exact relations of cultivation conditions and cell responses in
terms of viability, proliferation and metabolic activity should be further investigated.",
publisher = "Institute of Technical Sciences of SASA",
journal = "Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts",
title = "Optimization of Bioreactor Cultures of Glioblastoma Cells Immobilized in Alginate Microfibers",
pages = "8",
volume = "18",
url = "https://hdl.handle.net/21.15107/rcub_technorep_5033"
}

Petrović, J., Radonjić, M., Stojkovska, J.,& Obradović, B.. (2021). Optimization of Bioreactor Cultures of Glioblastoma Cells Immobilized in Alginate Microfibers. in Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts
Institute of Technical Sciences of SASA., 18, 8.
https://hdl.handle.net/21.15107/rcub_technorep_5033

Petrović J, Radonjić M, Stojkovska J, Obradović B. Optimization of Bioreactor Cultures of Glioblastoma Cells Immobilized in Alginate Microfibers. in Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts. 2021;18:8.
https://hdl.handle.net/21.15107/rcub_technorep_5033 .

Petrović, Jelena, Radonjić, Mia, Stojkovska, Jasmina, Obradović, Bojana, "Optimization of Bioreactor Cultures of Glioblastoma Cells Immobilized in Alginate Microfibers" in Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts, 18 (2021):8,
https://hdl.handle.net/21.15107/rcub_technorep_5033 .

TY  - CONF
AU  - Petrović, Jelena
AU  - Radonjić, Mia
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6211
AB  - Cancer is the second leading cause of death globally, making the search for its cure one of the most important challenges of the 21st century. With ethical questions regarding animal testing and inconsistency of results of cancer drug testing in standard two-dimensional (2D) monolayer cell cultures with the results in vivo, there is a pressing need for better in vitro models of human cancers that will provide more relevant systems for cancer drug screening. Three-dimensional (3D) in vitro systems based on natural polymers with immobilized cancer cells that mimic cancerous tissue and bioreactors that provide relevant chemical and physical signals could close the gap between 2D in vitro and in vivo cancer models. The aim of this study was to optimize culture conditions for the rat glioma cell line C6 immobilized in alginate microfibers in perfusion bioreactors in terms of cell density and perfusion rate. In this study we investigated following sets of parameters: perfusion rate of 0.12, 0.25 and 0.30 ml min-1 coupled with the cell density of 4∙106 cells ml-1 , and perfusion rate of 0.30 ml min-1 coupled with the cell density of 8∙106 cells ml-1 . Microfiber cultures under static conditions in Petri dishes served as controls. The results have shown that the perfusion rate of 0.30 ml min-1 in combination with the cell density of 8∙106 cells ml-1 yields higher cell viability and proliferation compared to the control static culture. These results indicate the importance of culture medium perfusion in the bioreactor for improved mass transfer of nutrients and oxygen to alginate microfibers so that the investigated system shows potentials for use as a model system in cancer research.
PB  - Materials Research Society of Serbia
C3  - 22nd Annual Conference YUCOMAT 2021, Herceg Novi, Montenegro
T1  - Optimization of in vitro conditions for 3D culture of rat glioma cells
SP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6211
ER  - 

@conference{
author = "Petrović, Jelena and Radonjić, Mia and Stojkovska, Jasmina and Obradović, Bojana",
year = "2021",
abstract = "Cancer is the second leading cause of death globally, making the search for its cure one of the most important challenges of the 21st century. With ethical questions regarding animal testing and inconsistency of results of cancer drug testing in standard two-dimensional (2D) monolayer cell cultures with the results in vivo, there is a pressing need for better in vitro models of human cancers that will provide more relevant systems for cancer drug screening. Three-dimensional (3D) in vitro systems based on natural polymers with immobilized cancer cells that mimic cancerous tissue and bioreactors that provide relevant chemical and physical signals could close the gap between 2D in vitro and in vivo cancer models. The aim of this study was to optimize culture conditions for the rat glioma cell line C6 immobilized in alginate microfibers in perfusion bioreactors in terms of cell density and perfusion rate. In this study we investigated following sets of parameters: perfusion rate of 0.12, 0.25 and 0.30 ml min-1 coupled with the cell density of 4∙106 cells ml-1 , and perfusion rate of 0.30 ml min-1 coupled with the cell density of 8∙106 cells ml-1 . Microfiber cultures under static conditions in Petri dishes served as controls. The results have shown that the perfusion rate of 0.30 ml min-1 in combination with the cell density of 8∙106 cells ml-1 yields higher cell viability and proliferation compared to the control static culture. These results indicate the importance of culture medium perfusion in the bioreactor for improved mass transfer of nutrients and oxygen to alginate microfibers so that the investigated system shows potentials for use as a model system in cancer research.",
publisher = "Materials Research Society of Serbia",
journal = "22nd Annual Conference YUCOMAT 2021, Herceg Novi, Montenegro",
title = "Optimization of in vitro conditions for 3D culture of rat glioma cells",
pages = "80",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6211"
}

Petrović, J., Radonjić, M., Stojkovska, J.,& Obradović, B.. (2021). Optimization of in vitro conditions for 3D culture of rat glioma cells. in 22nd Annual Conference YUCOMAT 2021, Herceg Novi, Montenegro
Materials Research Society of Serbia., 80.
https://hdl.handle.net/21.15107/rcub_technorep_6211

Petrović J, Radonjić M, Stojkovska J, Obradović B. Optimization of in vitro conditions for 3D culture of rat glioma cells. in 22nd Annual Conference YUCOMAT 2021, Herceg Novi, Montenegro. 2021;:80.
https://hdl.handle.net/21.15107/rcub_technorep_6211 .

Petrović, Jelena, Radonjić, Mia, Stojkovska, Jasmina, Obradović, Bojana, "Optimization of in vitro conditions for 3D culture of rat glioma cells" in 22nd Annual Conference YUCOMAT 2021, Herceg Novi, Montenegro (2021):80,
https://hdl.handle.net/21.15107/rcub_technorep_6211 .

TY  - CONF
AU  - Stojkovska, Jasmina
AU  - Stanković, Tijana
AU  - Dragoj, Miodrag
AU  - Petrović, Jelena
AU  - Radonjić, Mia
AU  - Pešić, Milica
AU  - Obradović, Bojana
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6353
AB  - The aim of this work was to develop a 3D microenvironment for glioblastoma brain tumor engineering based on alginate
hydrogels as a matrix for cell immobilization followed by cultivation in a biomimetic perfusion bioreactor. Alginate
microfibers with immobilized cells were obtained by a simple extrusion technique. We have examined the influence of the
needle diameter (22G - 28G), cell density in alginate solution (1 x 106 - 8 x 106 cells/ml) and different cancer cell lines (rat
C6 and human U251 and U87) on cell immobilization efficiency and viability. The best alginate microfibers (500 µm in
diameter) with all immobilized cells were obtained by applying a 25G needle with a minimal cell density of 4 x 106 cells/ml.
The obtained microfibers with immobilized cells (C6 and U87) were cultivated in a perfusion bioreactor at the continuous
medium flowrate in the range 0.05-0.30 ml/min over short- and long-term cultivation periods. The results have shown that
the flowrate of 0.30 ml/min, corresponding to the superficial velocity of 100 µm/s, in combination with the C6 cell density
of 8 x 106 cells/ml in short-term studies yielded higher cell viabilities and proliferation as compared to the control static
culture. In addition, U87 cells immobilized in alginate microfibers at the density of 4 x 106 cells/ml after long-term
cultivation at the medium flowrate of 0.05 ml/min (superficial velocity of 15 µm/s) stayed viable.
The overall results have shown potentials of the applied approach for tumor engineering provided optimization of
cultivation conditions for each cell type.
C3  - 6th World TERMIS Conference 2021 Abstract Book
T1  - Development of 3D microenvironment for engineering of glioblastoma brain tumor
SP  - 930
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6353
ER  - 

@conference{
author = "Stojkovska, Jasmina and Stanković, Tijana and Dragoj, Miodrag and Petrović, Jelena and Radonjić, Mia and Pešić, Milica and Obradović, Bojana",
year = "2021",
abstract = "The aim of this work was to develop a 3D microenvironment for glioblastoma brain tumor engineering based on alginate
hydrogels as a matrix for cell immobilization followed by cultivation in a biomimetic perfusion bioreactor. Alginate
microfibers with immobilized cells were obtained by a simple extrusion technique. We have examined the influence of the
needle diameter (22G - 28G), cell density in alginate solution (1 x 106 - 8 x 106 cells/ml) and different cancer cell lines (rat
C6 and human U251 and U87) on cell immobilization efficiency and viability. The best alginate microfibers (500 µm in
diameter) with all immobilized cells were obtained by applying a 25G needle with a minimal cell density of 4 x 106 cells/ml.
The obtained microfibers with immobilized cells (C6 and U87) were cultivated in a perfusion bioreactor at the continuous
medium flowrate in the range 0.05-0.30 ml/min over short- and long-term cultivation periods. The results have shown that
the flowrate of 0.30 ml/min, corresponding to the superficial velocity of 100 µm/s, in combination with the C6 cell density
of 8 x 106 cells/ml in short-term studies yielded higher cell viabilities and proliferation as compared to the control static
culture. In addition, U87 cells immobilized in alginate microfibers at the density of 4 x 106 cells/ml after long-term
cultivation at the medium flowrate of 0.05 ml/min (superficial velocity of 15 µm/s) stayed viable.
The overall results have shown potentials of the applied approach for tumor engineering provided optimization of
cultivation conditions for each cell type.",
journal = "6th World TERMIS Conference 2021 Abstract Book",
title = "Development of 3D microenvironment for engineering of glioblastoma brain tumor",
pages = "930",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6353"
}

Stojkovska, J., Stanković, T., Dragoj, M., Petrović, J., Radonjić, M., Pešić, M.,& Obradović, B.. (2021). Development of 3D microenvironment for engineering of glioblastoma brain tumor. in 6th World TERMIS Conference 2021 Abstract Book, 930.
https://hdl.handle.net/21.15107/rcub_technorep_6353

Stojkovska J, Stanković T, Dragoj M, Petrović J, Radonjić M, Pešić M, Obradović B. Development of 3D microenvironment for engineering of glioblastoma brain tumor. in 6th World TERMIS Conference 2021 Abstract Book. 2021;:930.
https://hdl.handle.net/21.15107/rcub_technorep_6353 .

Stojkovska, Jasmina, Stanković, Tijana, Dragoj, Miodrag, Petrović, Jelena, Radonjić, Mia, Pešić, Milica, Obradović, Bojana, "Development of 3D microenvironment for engineering of glioblastoma brain tumor" in 6th World TERMIS Conference 2021 Abstract Book (2021):930,
https://hdl.handle.net/21.15107/rcub_technorep_6353 .