TY  - JOUR
AU  - Panczyszyn, Elzbieta
AU  - Saverio, Valentina
AU  - Monzani, Romina
AU  - Gagliardi, Mara
AU  - Petrović, Jelena
AU  - Stojkovska, Jasmina
AU  - Collavin, Licio
AU  - Corazzari, Marco
PY  - 2024-12
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/7318
AB  - Human osteosarcoma (OS) is a relatively rare malignancy preferentially affecting long body bones which prognosis is often poor also due to the lack of effective therapies. Clinical management of this cancer basically relies on surgical removal of primary tumor coupled with radio/chemotherapy. Unfortunately, most osteosarcoma cells are resistant to conventional therapy, with the undergoing epithelial-mesenchymal transition (EMT) giving rise to gene expression reprogramming, thus increasing cancer cell invasiveness and metastatic potential. Alternative clinical approaches are thus urgently needed. In this context, the recently described ferroptotic cell death represents an attractive new strategy to efficiently kill cancer cells, since most chemoresistant and mesenchymal-shaped tumors display high susceptibility to pro-ferroptotic compounds. However, cancer cells have also evolved anti-ferroptotic strategies, which somehow sustain their survival upon ferroptosis induction. Indeed, here we show that osteosarcoma cell lines display heterogeneous sensitivity to ferroptosis execution, correlating with the mesenchymal phenotype, which is consistently affected by the expression of the well-known anti-ferroptotic factor ferroptosis suppressor protein 1 (FSP1). Interestingly, inhibiting the activity or expression of FSP1 restores cancer cell sensitivity to ferroptosis. Moreover, we also found that: i) AKRs might also contribute to resistance; ii) NRF2 enhances FSP1 expression upon ferroptosis induction; while iii) p53 contributes to the regulation of FSP1 basal expression in OS cells. In conclusion, FSP1 expression can potentially be used as a valuable predictive marker of OS sensitivity to ferroptosis and as a new potential therapeutic target.
PB  - Springer Nature
T2  - Cell Death Discovery
T1  - FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target
IS  - 1
SP  - 87
VL  - 10
DO  - 10.1038/s41420-024-01854-2
ER  - 

@article{
author = "Panczyszyn, Elzbieta and Saverio, Valentina and Monzani, Romina and Gagliardi, Mara and Petrović, Jelena and Stojkovska, Jasmina and Collavin, Licio and Corazzari, Marco",
year = "2024-12",
abstract = "Human osteosarcoma (OS) is a relatively rare malignancy preferentially affecting long body bones which prognosis is often poor also due to the lack of effective therapies. Clinical management of this cancer basically relies on surgical removal of primary tumor coupled with radio/chemotherapy. Unfortunately, most osteosarcoma cells are resistant to conventional therapy, with the undergoing epithelial-mesenchymal transition (EMT) giving rise to gene expression reprogramming, thus increasing cancer cell invasiveness and metastatic potential. Alternative clinical approaches are thus urgently needed. In this context, the recently described ferroptotic cell death represents an attractive new strategy to efficiently kill cancer cells, since most chemoresistant and mesenchymal-shaped tumors display high susceptibility to pro-ferroptotic compounds. However, cancer cells have also evolved anti-ferroptotic strategies, which somehow sustain their survival upon ferroptosis induction. Indeed, here we show that osteosarcoma cell lines display heterogeneous sensitivity to ferroptosis execution, correlating with the mesenchymal phenotype, which is consistently affected by the expression of the well-known anti-ferroptotic factor ferroptosis suppressor protein 1 (FSP1). Interestingly, inhibiting the activity or expression of FSP1 restores cancer cell sensitivity to ferroptosis. Moreover, we also found that: i) AKRs might also contribute to resistance; ii) NRF2 enhances FSP1 expression upon ferroptosis induction; while iii) p53 contributes to the regulation of FSP1 basal expression in OS cells. In conclusion, FSP1 expression can potentially be used as a valuable predictive marker of OS sensitivity to ferroptosis and as a new potential therapeutic target.",
publisher = "Springer Nature",
journal = "Cell Death Discovery",
title = "FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target",
number = "1",
pages = "87",
volume = "10",
doi = "10.1038/s41420-024-01854-2"
}

Panczyszyn, E., Saverio, V., Monzani, R., Gagliardi, M., Petrović, J., Stojkovska, J., Collavin, L.,& Corazzari, M.. (2024-12). FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target. in Cell Death Discovery
Springer Nature., 10(1), 87.
https://doi.org/10.1038/s41420-024-01854-2

Panczyszyn E, Saverio V, Monzani R, Gagliardi M, Petrović J, Stojkovska J, Collavin L, Corazzari M. FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target. in Cell Death Discovery. 2024;10(1):87.
doi:10.1038/s41420-024-01854-2 .

Panczyszyn, Elzbieta, Saverio, Valentina, Monzani, Romina, Gagliardi, Mara, Petrović, Jelena, Stojkovska, Jasmina, Collavin, Licio, Corazzari, Marco, "FSP1 is a predictive biomarker of osteosarcoma cells’ susceptibility to ferroptotic cell death and a potential therapeutic target" in Cell Death Discovery, 10, no. 1 (2024-12):87,
https://doi.org/10.1038/s41420-024-01854-2 . .

TY  - CONF
AU  - Zvicer, Jovana
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2023
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6955
AB  - Developing new biomaterials for bone tissue engineering is of vital importance due to the increasing demand for bone transplants resulting from various causes, such as trauma, tumors, infection, and genetic conditions. To address this persistent need, biomaterials for bone tissue engineering must fulfil several critical requirements, such as mimicking the hierarchical structure of complex bone tissue composed of organic and inorganic components, possessing suitable mechanical properties, pore size, and porosity, as well as an appropriate degradation rate. Our research group has successfully developed two promising biomaterials for bone tissue engineering, utilizing a combination of bioactive glass (BAG) or β-tricalcium phosphate (β-TCP) - undoped or doped with Mg2+, and different natural polymers, such as gellan gum (GG) and alginate (ALG). Obtained scaffolds were assessed in terms of porosity and pore size distribution, and mechanical properties under physiological levels of mechanical compression (337.5 μm/s loading rate, 10% strain) using a dynamic compression bioreactor coupled with medium perfusion over a 14-day period. The mechanical properties of the β-TCP-ALG scaffolds were influenced by the composition of calcium phosphate fillers, with improvements observed as Ca2+ concentration increased while Mg2+ concentration decreased. These properties were significantly higher compared to the mechanical properties of BAG-GG scaffolds. Bioactivity of the scaffolds was evaluated under static and biomimetic conditions in the perfusion bioreactor, with a continuous flow of simulated body fluid (SBF) at a superficial velocity of 400 µm/s. The formation of hydroxyapatite (HAp) within the BAG-based scaffolds was studied for 14 days, while for β-TCP-based scaffolds, the studies continued for 28 days. The results revealed a remarkable increase in HAp formation under bioreactor conditions compared to static controls in both types of scaffolds, with HAp crystals exhibiting a more uniform distribution and a distinctive cauliflower-like morphology throughout the scaffolds. However, bioactivity was more profound for the BAG-GG scaffolds compared to β-TCP-ALG scaffolds due to additional gelation of alginate around the incorporated fillers. Physiologically relevant characterization with the aid of biomimetic bioreactors has unveiled the promising potential of novel composite scaffolds for bone tissue engineering, while also highlighting the importance of carefully balancing different scaffold characteristics, such as mechanical strength and bioactivity, to develop optimal scaffolds tailored for specific applications.
PB  - Novi Sad : Faculty of Technology
C3  - Programme and The Book of Abstracts / 15th ECerS Conference for Young Scientists in Ceramics, CYSC-2023, October 11-14, 2023, Novi Sad, Serbia
T1  - Development and characterization of composites for bone tissue engineering with the aid of biomimetic bioreactors
SP  - 27
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6955
ER  - 

@conference{
author = "Zvicer, Jovana and Stojkovska, Jasmina and Obradović, Bojana",
year = "2023",
abstract = "Developing new biomaterials for bone tissue engineering is of vital importance due to the increasing demand for bone transplants resulting from various causes, such as trauma, tumors, infection, and genetic conditions. To address this persistent need, biomaterials for bone tissue engineering must fulfil several critical requirements, such as mimicking the hierarchical structure of complex bone tissue composed of organic and inorganic components, possessing suitable mechanical properties, pore size, and porosity, as well as an appropriate degradation rate. Our research group has successfully developed two promising biomaterials for bone tissue engineering, utilizing a combination of bioactive glass (BAG) or β-tricalcium phosphate (β-TCP) - undoped or doped with Mg2+, and different natural polymers, such as gellan gum (GG) and alginate (ALG). Obtained scaffolds were assessed in terms of porosity and pore size distribution, and mechanical properties under physiological levels of mechanical compression (337.5 μm/s loading rate, 10% strain) using a dynamic compression bioreactor coupled with medium perfusion over a 14-day period. The mechanical properties of the β-TCP-ALG scaffolds were influenced by the composition of calcium phosphate fillers, with improvements observed as Ca2+ concentration increased while Mg2+ concentration decreased. These properties were significantly higher compared to the mechanical properties of BAG-GG scaffolds. Bioactivity of the scaffolds was evaluated under static and biomimetic conditions in the perfusion bioreactor, with a continuous flow of simulated body fluid (SBF) at a superficial velocity of 400 µm/s. The formation of hydroxyapatite (HAp) within the BAG-based scaffolds was studied for 14 days, while for β-TCP-based scaffolds, the studies continued for 28 days. The results revealed a remarkable increase in HAp formation under bioreactor conditions compared to static controls in both types of scaffolds, with HAp crystals exhibiting a more uniform distribution and a distinctive cauliflower-like morphology throughout the scaffolds. However, bioactivity was more profound for the BAG-GG scaffolds compared to β-TCP-ALG scaffolds due to additional gelation of alginate around the incorporated fillers. Physiologically relevant characterization with the aid of biomimetic bioreactors has unveiled the promising potential of novel composite scaffolds for bone tissue engineering, while also highlighting the importance of carefully balancing different scaffold characteristics, such as mechanical strength and bioactivity, to develop optimal scaffolds tailored for specific applications.",
publisher = "Novi Sad : Faculty of Technology",
journal = "Programme and The Book of Abstracts / 15th ECerS Conference for Young Scientists in Ceramics, CYSC-2023, October 11-14, 2023, Novi Sad, Serbia",
title = "Development and characterization of composites for bone tissue engineering with the aid of biomimetic bioreactors",
pages = "27",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6955"
}

Zvicer, J., Stojkovska, J.,& Obradović, B.. (2023). Development and characterization of composites for bone tissue engineering with the aid of biomimetic bioreactors. in Programme and The Book of Abstracts / 15th ECerS Conference for Young Scientists in Ceramics, CYSC-2023, October 11-14, 2023, Novi Sad, Serbia
Novi Sad : Faculty of Technology., 27.
https://hdl.handle.net/21.15107/rcub_technorep_6955

Zvicer J, Stojkovska J, Obradović B. Development and characterization of composites for bone tissue engineering with the aid of biomimetic bioreactors. in Programme and The Book of Abstracts / 15th ECerS Conference for Young Scientists in Ceramics, CYSC-2023, October 11-14, 2023, Novi Sad, Serbia. 2023;:27.
https://hdl.handle.net/21.15107/rcub_technorep_6955 .

Zvicer, Jovana, Stojkovska, Jasmina, Obradović, Bojana, "Development and characterization of composites for bone tissue engineering with the aid of biomimetic bioreactors" in Programme and The Book of Abstracts / 15th ECerS Conference for Young Scientists in Ceramics, CYSC-2023, October 11-14, 2023, Novi Sad, Serbia (2023):27,
https://hdl.handle.net/21.15107/rcub_technorep_6955 .

TY  - CONF
AU  - Zvicer, Jovana
AU  - Stojkovska, Jasmina
AU  - Milošević, Mia
AU  - Veljović, Đorđe
AU  - Obradović, Bojana
PY  - 2023
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6956
AB  - Development of novel biomaterials for use in biomedical applications requires careful assessment due to the intended interactions with cells and tissues. Understanding biocompatibility, non-toxicity, and capability of promoting desired biological responses requires thorough characterization of biomaterial, including its chemical composition, surface properties, mechanical strength, degradation rate, etc. Traditional in vitro methods for evaluating biomaterials in cell monolayers are convenient but limited by the lack of specific biophysical signals found in vivo, which can lead to unreliable results. This in vitro-in vivo gap can result in the unnecessary sacrifice of a large number of animals for testing purposes. Therefore, there is a need for alternative approaches that beter mimic the in vivo environment and accurately predict the behavior of the biomaterial after implantation. Biomimetic bioreactors are primarily developed for tissue engineering to provide the key biochemical (e.g., nutrients, gases, growth factors) and biophysical signals (e.g., shear stress, hydrostatic pressure, mechanical strains) found in vivo and thus could be indispensable tools in physiologically relevant biomaterial assessment. Our group introduced the application of two biomimetic bioreactors for the physiologically relevant characterization of two types of composite biomaterials aimed for bone and osteochondral tissue engineering. In specific, macroporous composite scaffolds were produced using two natural polymers (gellan gum and alginate) as matrices imitating organic phase of bone tissue with incorporated particulate bioactive glass (BAG) and β-tricalcium phosphate (β-TCP) as hydroxyapatite (HAp) precursors. In addition, in osteochondral scaffolds, gellan gum hydrogel served as a cartilaginous layer on top of the porous composite base. Integrity and mechanical properties of all prepared scaffolds were monitored for 14 days under physiological levels of mechanical compression (up to 10% strain, compression rate 337.5 µm s-1) in a bioreactor with dynamic compression and medium perfusion. Bioactivity and HAp formation within the scaffolds were investigated in a perfusion bioreactor under the flow of simulated body fluid for up to 28 days. The scaffolds were assessed by SEM, EDS, and XRD analyses indicating a significant increase in HAp formation under bioreactor conditions as compared to static controls in all investigated samples. Moreover, the formed HAp crystals were more uniformly distributed throughout the scaffolds showing a more cauliflower-like morphology and thus, indicating potentials for bone/osteochondral tissue engineering applications. The obtained results confirm the high influence of experimental conditions on the outcomes of biomaterial characterization and importance of closely mimicking physiological conditions, thus puting forward biomimetic bioreactors as a means in this direction.
PB  - Davos : AO Research Institute
C3  - ARI Abstracts Periodical
T1  - BIOMIMETIC BIOREACTORS AS A TOOL FOR MORE RELEVANT BIOMATERIAL ASSESSMENT
IS  - Collection 3
SP  - 313
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6956
ER  - 

@conference{
author = "Zvicer, Jovana and Stojkovska, Jasmina and Milošević, Mia and Veljović, Đorđe and Obradović, Bojana",
year = "2023",
abstract = "Development of novel biomaterials for use in biomedical applications requires careful assessment due to the intended interactions with cells and tissues. Understanding biocompatibility, non-toxicity, and capability of promoting desired biological responses requires thorough characterization of biomaterial, including its chemical composition, surface properties, mechanical strength, degradation rate, etc. Traditional in vitro methods for evaluating biomaterials in cell monolayers are convenient but limited by the lack of specific biophysical signals found in vivo, which can lead to unreliable results. This in vitro-in vivo gap can result in the unnecessary sacrifice of a large number of animals for testing purposes. Therefore, there is a need for alternative approaches that beter mimic the in vivo environment and accurately predict the behavior of the biomaterial after implantation. Biomimetic bioreactors are primarily developed for tissue engineering to provide the key biochemical (e.g., nutrients, gases, growth factors) and biophysical signals (e.g., shear stress, hydrostatic pressure, mechanical strains) found in vivo and thus could be indispensable tools in physiologically relevant biomaterial assessment. Our group introduced the application of two biomimetic bioreactors for the physiologically relevant characterization of two types of composite biomaterials aimed for bone and osteochondral tissue engineering. In specific, macroporous composite scaffolds were produced using two natural polymers (gellan gum and alginate) as matrices imitating organic phase of bone tissue with incorporated particulate bioactive glass (BAG) and β-tricalcium phosphate (β-TCP) as hydroxyapatite (HAp) precursors. In addition, in osteochondral scaffolds, gellan gum hydrogel served as a cartilaginous layer on top of the porous composite base. Integrity and mechanical properties of all prepared scaffolds were monitored for 14 days under physiological levels of mechanical compression (up to 10% strain, compression rate 337.5 µm s-1) in a bioreactor with dynamic compression and medium perfusion. Bioactivity and HAp formation within the scaffolds were investigated in a perfusion bioreactor under the flow of simulated body fluid for up to 28 days. The scaffolds were assessed by SEM, EDS, and XRD analyses indicating a significant increase in HAp formation under bioreactor conditions as compared to static controls in all investigated samples. Moreover, the formed HAp crystals were more uniformly distributed throughout the scaffolds showing a more cauliflower-like morphology and thus, indicating potentials for bone/osteochondral tissue engineering applications. The obtained results confirm the high influence of experimental conditions on the outcomes of biomaterial characterization and importance of closely mimicking physiological conditions, thus puting forward biomimetic bioreactors as a means in this direction.",
publisher = "Davos : AO Research Institute",
journal = "ARI Abstracts Periodical",
title = "BIOMIMETIC BIOREACTORS AS A TOOL FOR MORE RELEVANT BIOMATERIAL ASSESSMENT",
number = "Collection 3",
pages = "313",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6956"
}

Zvicer, J., Stojkovska, J., Milošević, M., Veljović, Đ.,& Obradović, B.. (2023). BIOMIMETIC BIOREACTORS AS A TOOL FOR MORE RELEVANT BIOMATERIAL ASSESSMENT. in ARI Abstracts Periodical
Davos : AO Research Institute.(Collection 3), 313.
https://hdl.handle.net/21.15107/rcub_technorep_6956

Zvicer J, Stojkovska J, Milošević M, Veljović Đ, Obradović B. BIOMIMETIC BIOREACTORS AS A TOOL FOR MORE RELEVANT BIOMATERIAL ASSESSMENT. in ARI Abstracts Periodical. 2023;(Collection 3):313.
https://hdl.handle.net/21.15107/rcub_technorep_6956 .

Zvicer, Jovana, Stojkovska, Jasmina, Milošević, Mia, Veljović, Đorđe, Obradović, Bojana, "BIOMIMETIC BIOREACTORS AS A TOOL FOR MORE RELEVANT BIOMATERIAL ASSESSMENT" in ARI Abstracts Periodical, no. Collection 3 (2023):313,
https://hdl.handle.net/21.15107/rcub_technorep_6956 .

TY  - CONF
AU  - Zvicer, Jovana
AU  - Stojkovska, Jasmina
AU  - Veljović, Đorđe
AU  - Milošević, Mia
AU  - Obradović, Bojana
PY  - 2023
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6957
AB  - Comprehensive preclinical studies are essential for the development of novel biomaterials that can be used in biomedical applications. However, traditional methods used for the evaluation of biomaterials have certain limitations. In vitro testing in cell monolayers is fast and easily accessible, but the 2D environment can affect cell metabolism and morphology, leading to unreliable results. On the other hand, in vivo animal studies are complex, time-consuming, expensive, and raise ethical concerns. Biomimetic bioreactors, primarily developed for tissue engineering to provide a physiologically relevant, strictly controlled environment that mimics the conditions in specific tissues or organs, could be indispensable tools in physiologically relevant biomaterial characterization and step between in vitro and in vivo studies. They offer the majority or all the necessary biochemical (e.g. pH, nutrients, gases, growth factors) and biophysical signals (e.g., shear stress, hydrostatic pressure, mechanical strains) highly relevant for biomaterial assessment and prediction of material behavior after implantation. Our group has developed two types of potential biomaterials aimed for bone and osteochondral tissue engineering based on bioactive glass (BAG), β-tricalcium phosphate (β-TCP), and different natural polymers (gellan gum and alginate). Scaffolds' integrity and mechanical properties were monitored continuously under the physiological level of mechanical compression using a dynamic compression bioreactor coupled with medium perfusion during 14 days. Formation of hydroxyapatite (HAp) within the scaffolds was investigated in a perfusion bioreactor, in the presence of simulated body fluid (SBF) during 14 and 28 days for scaffolds based on BAG and β-TCP, respectively. SEM, EDS, and XRD results have shown a significant increase in the formation of HAp under bioreactor conditions compared to static control conditions. Beyond that, formed HAp crystals were more uniformly distributed throughout scaffolds and presented more cauliflower-like morphology. The obtained results demonstrated the utilization potential of biomimetic bioreactors in physiologically relevant biomaterial characterization.
C3  - Book of Abstract / 3rd YCN Workshop, 19th to 21st April 2023, Aveiro, Portugal
T1  - HOW NOVEL BIOMATERIALS BASED ON BIOACTIVE GLASS AND β-TRICALCIUM PHOSPHATE CAN BE EVALUATED UNDER PHYSIOLOGICALLY RELEVANT CONDITIONS?
SP  - 23
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6957
ER  - 

@conference{
author = "Zvicer, Jovana and Stojkovska, Jasmina and Veljović, Đorđe and Milošević, Mia and Obradović, Bojana",
year = "2023",
abstract = "Comprehensive preclinical studies are essential for the development of novel biomaterials that can be used in biomedical applications. However, traditional methods used for the evaluation of biomaterials have certain limitations. In vitro testing in cell monolayers is fast and easily accessible, but the 2D environment can affect cell metabolism and morphology, leading to unreliable results. On the other hand, in vivo animal studies are complex, time-consuming, expensive, and raise ethical concerns. Biomimetic bioreactors, primarily developed for tissue engineering to provide a physiologically relevant, strictly controlled environment that mimics the conditions in specific tissues or organs, could be indispensable tools in physiologically relevant biomaterial characterization and step between in vitro and in vivo studies. They offer the majority or all the necessary biochemical (e.g. pH, nutrients, gases, growth factors) and biophysical signals (e.g., shear stress, hydrostatic pressure, mechanical strains) highly relevant for biomaterial assessment and prediction of material behavior after implantation. Our group has developed two types of potential biomaterials aimed for bone and osteochondral tissue engineering based on bioactive glass (BAG), β-tricalcium phosphate (β-TCP), and different natural polymers (gellan gum and alginate). Scaffolds' integrity and mechanical properties were monitored continuously under the physiological level of mechanical compression using a dynamic compression bioreactor coupled with medium perfusion during 14 days. Formation of hydroxyapatite (HAp) within the scaffolds was investigated in a perfusion bioreactor, in the presence of simulated body fluid (SBF) during 14 and 28 days for scaffolds based on BAG and β-TCP, respectively. SEM, EDS, and XRD results have shown a significant increase in the formation of HAp under bioreactor conditions compared to static control conditions. Beyond that, formed HAp crystals were more uniformly distributed throughout scaffolds and presented more cauliflower-like morphology. The obtained results demonstrated the utilization potential of biomimetic bioreactors in physiologically relevant biomaterial characterization.",
journal = "Book of Abstract / 3rd YCN Workshop, 19th to 21st April 2023, Aveiro, Portugal",
title = "HOW NOVEL BIOMATERIALS BASED ON BIOACTIVE GLASS AND β-TRICALCIUM PHOSPHATE CAN BE EVALUATED UNDER PHYSIOLOGICALLY RELEVANT CONDITIONS?",
pages = "23",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6957"
}

Zvicer, J., Stojkovska, J., Veljović, Đ., Milošević, M.,& Obradović, B.. (2023). HOW NOVEL BIOMATERIALS BASED ON BIOACTIVE GLASS AND β-TRICALCIUM PHOSPHATE CAN BE EVALUATED UNDER PHYSIOLOGICALLY RELEVANT CONDITIONS?. in Book of Abstract / 3rd YCN Workshop, 19th to 21st April 2023, Aveiro, Portugal, 23.
https://hdl.handle.net/21.15107/rcub_technorep_6957

Zvicer J, Stojkovska J, Veljović Đ, Milošević M, Obradović B. HOW NOVEL BIOMATERIALS BASED ON BIOACTIVE GLASS AND β-TRICALCIUM PHOSPHATE CAN BE EVALUATED UNDER PHYSIOLOGICALLY RELEVANT CONDITIONS?. in Book of Abstract / 3rd YCN Workshop, 19th to 21st April 2023, Aveiro, Portugal. 2023;:23.
https://hdl.handle.net/21.15107/rcub_technorep_6957 .

Zvicer, Jovana, Stojkovska, Jasmina, Veljović, Đorđe, Milošević, Mia, Obradović, Bojana, "HOW NOVEL BIOMATERIALS BASED ON BIOACTIVE GLASS AND β-TRICALCIUM PHOSPHATE CAN BE EVALUATED UNDER PHYSIOLOGICALLY RELEVANT CONDITIONS?" in Book of Abstract / 3rd YCN Workshop, 19th to 21st April 2023, Aveiro, Portugal (2023):23,
https://hdl.handle.net/21.15107/rcub_technorep_6957 .

TY  - JOUR
AU  - Vidović, Srđan
AU  - Stojkovska, Jasmina
AU  - Stevanović, Milan
AU  - Balanč, Bojana
AU  - Vukašinović-Sekulić, Maja
AU  - Marinković, Aleksandar
AU  - Obradović, Bojana
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5105
AB  - In this work, nanocomposite fibres and microfibres based on alginate and poly(vinyl alcohol) (PVA) with silver nanoparticles (AgNPs) were produced and characterized for potential application as antibacterial wound dressings. PVA/Ag/Na-alginate colloid solution was used for the preparation of the fibres by a simple extrusion technique followed by freezing-thawing cycles. UV-Visible spectroscopy confirmed successful preservation of AgNPs in fibres while Fourier transform infrared spectroscopy has shown a balanced combined effect on the Ca-alginate spatial arrangement with the addition of both AgNPs and PVA. The presence of PVA in fibres induced an increase in the swelling degree as compared with that of Ag/Ca-alginate fibres (approx. 28 versus approx. 14). Still, the initially produced PVA/Ca-alginate fibres were mechanically weaker than Ca-alginate fibres, but after drying and rehydration exhibited better mechanical properties. Also, the obtained fibres released AgNPs and/or silver ions at the concentration of approximately 2.6 μg cm -3 leading to bacteriostatic effects against Staphylococcus aureus and Escherichia coli. These results are relevant for practical utilization of the fibres, which could be stored and applied in the dry form with preserved mechanical stability, sorption capacity and antibacterial activity.
PB  - Royal Society Publishing
T2  - Royal Society Open Science
T1  - Effects of poly(vinyl alcohol) blending with Ag/alginate solutions to form nanocomposite fibres for potential use as antibacterial wound dressings
IS  - 3
SP  - 211517
VL  - 9
DO  - 10.1098/rsos.211517
ER  - 

@article{
author = "Vidović, Srđan and Stojkovska, Jasmina and Stevanović, Milan and Balanč, Bojana and Vukašinović-Sekulić, Maja and Marinković, Aleksandar and Obradović, Bojana",
year = "2022",
abstract = "In this work, nanocomposite fibres and microfibres based on alginate and poly(vinyl alcohol) (PVA) with silver nanoparticles (AgNPs) were produced and characterized for potential application as antibacterial wound dressings. PVA/Ag/Na-alginate colloid solution was used for the preparation of the fibres by a simple extrusion technique followed by freezing-thawing cycles. UV-Visible spectroscopy confirmed successful preservation of AgNPs in fibres while Fourier transform infrared spectroscopy has shown a balanced combined effect on the Ca-alginate spatial arrangement with the addition of both AgNPs and PVA. The presence of PVA in fibres induced an increase in the swelling degree as compared with that of Ag/Ca-alginate fibres (approx. 28 versus approx. 14). Still, the initially produced PVA/Ca-alginate fibres were mechanically weaker than Ca-alginate fibres, but after drying and rehydration exhibited better mechanical properties. Also, the obtained fibres released AgNPs and/or silver ions at the concentration of approximately 2.6 μg cm -3 leading to bacteriostatic effects against Staphylococcus aureus and Escherichia coli. These results are relevant for practical utilization of the fibres, which could be stored and applied in the dry form with preserved mechanical stability, sorption capacity and antibacterial activity.",
publisher = "Royal Society Publishing",
journal = "Royal Society Open Science",
title = "Effects of poly(vinyl alcohol) blending with Ag/alginate solutions to form nanocomposite fibres for potential use as antibacterial wound dressings",
number = "3",
pages = "211517",
volume = "9",
doi = "10.1098/rsos.211517"
}

Vidović, S., Stojkovska, J., Stevanović, M., Balanč, B., Vukašinović-Sekulić, M., Marinković, A.,& Obradović, B.. (2022). Effects of poly(vinyl alcohol) blending with Ag/alginate solutions to form nanocomposite fibres for potential use as antibacterial wound dressings. in Royal Society Open Science
Royal Society Publishing., 9(3), 211517.
https://doi.org/10.1098/rsos.211517

Vidović S, Stojkovska J, Stevanović M, Balanč B, Vukašinović-Sekulić M, Marinković A, Obradović B. Effects of poly(vinyl alcohol) blending with Ag/alginate solutions to form nanocomposite fibres for potential use as antibacterial wound dressings. in Royal Society Open Science. 2022;9(3):211517.
doi:10.1098/rsos.211517 .

Vidović, Srđan, Stojkovska, Jasmina, Stevanović, Milan, Balanč, Bojana, Vukašinović-Sekulić, Maja, Marinković, Aleksandar, Obradović, Bojana, "Effects of poly(vinyl alcohol) blending with Ag/alginate solutions to form nanocomposite fibres for potential use as antibacterial wound dressings" in Royal Society Open Science, 9, no. 3 (2022):211517,
https://doi.org/10.1098/rsos.211517 . .

TY  - CONF
AU  - Obradović, Bojana
AU  - Stojkovska, Jasmina
AU  - Radovanović, Željko
AU  - Matić, Tamara
AU  - Petrović, Rada
AU  - Janaćković, Đorđe
AU  - Veljović, Đorđe
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6682
AB  - Biomaterials engineering is one of the strongest research areas at the Faculty of Technology and Metallurgy (FTM), University of Belgrade including development of novel biomaterials for orthopaedic and dental applications. Especially, synthesis and physico-chemical characterization methods are well established resulting in variety of novel inorganic, polymer and composite biomaterials produced in different forms with controlled compositions and structures. Still, expertise in further advancement of the research results towards utilization in medical devices is lacking. The ExcellMater Horizon 2020 project aims to further advance the scientific and technological capacity of the Faculty in this area by twinning the knowledge from the three European partners, internationally leading institutions, with recognized expertise in biological characterization methods, intellectual property protection and utilization, evaluation of health technologies and regulatory aspects of medical devices. The aim of the project is also to increase visibility of scientific research and enhance collaboration of engineers at FTM with life scientists, medical doctors and pharmacists as well as with industry. Here, we will present some of the novel bioceramic and composite biomaterials developed at FTM aimed for potential applications in orthopaedics, dentistry, bone tissue engineering, and cancer research.
PB  - Consiglio Nazionale delle Ricerche Istituto di Struttura della Materia
C3  - Conference proceedings / 3rd biennial International Conference: Biomaterials and novel technologies for healthcare BIOMAH, October 18-21, 2022 Rome – Italy
T1  - The ExcellMater project for advancement of novel bioceramic and composite biomaterials for medical applications
EP  - 197
SP  - 196
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6682
ER  - 

@conference{
author = "Obradović, Bojana and Stojkovska, Jasmina and Radovanović, Željko and Matić, Tamara and Petrović, Rada and Janaćković, Đorđe and Veljović, Đorđe",
year = "2022",
abstract = "Biomaterials engineering is one of the strongest research areas at the Faculty of Technology and Metallurgy (FTM), University of Belgrade including development of novel biomaterials for orthopaedic and dental applications. Especially, synthesis and physico-chemical characterization methods are well established resulting in variety of novel inorganic, polymer and composite biomaterials produced in different forms with controlled compositions and structures. Still, expertise in further advancement of the research results towards utilization in medical devices is lacking. The ExcellMater Horizon 2020 project aims to further advance the scientific and technological capacity of the Faculty in this area by twinning the knowledge from the three European partners, internationally leading institutions, with recognized expertise in biological characterization methods, intellectual property protection and utilization, evaluation of health technologies and regulatory aspects of medical devices. The aim of the project is also to increase visibility of scientific research and enhance collaboration of engineers at FTM with life scientists, medical doctors and pharmacists as well as with industry. Here, we will present some of the novel bioceramic and composite biomaterials developed at FTM aimed for potential applications in orthopaedics, dentistry, bone tissue engineering, and cancer research.",
publisher = "Consiglio Nazionale delle Ricerche Istituto di Struttura della Materia",
journal = "Conference proceedings / 3rd biennial International Conference: Biomaterials and novel technologies for healthcare BIOMAH, October 18-21, 2022 Rome – Italy",
title = "The ExcellMater project for advancement of novel bioceramic and composite biomaterials for medical applications",
pages = "197-196",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6682"
}

Obradović, B., Stojkovska, J., Radovanović, Ž., Matić, T., Petrović, R., Janaćković, Đ.,& Veljović, Đ.. (2022). The ExcellMater project for advancement of novel bioceramic and composite biomaterials for medical applications. in Conference proceedings / 3rd biennial International Conference: Biomaterials and novel technologies for healthcare BIOMAH, October 18-21, 2022 Rome – Italy
Consiglio Nazionale delle Ricerche Istituto di Struttura della Materia., 196-197.
https://hdl.handle.net/21.15107/rcub_technorep_6682

Obradović B, Stojkovska J, Radovanović Ž, Matić T, Petrović R, Janaćković Đ, Veljović Đ. The ExcellMater project for advancement of novel bioceramic and composite biomaterials for medical applications. in Conference proceedings / 3rd biennial International Conference: Biomaterials and novel technologies for healthcare BIOMAH, October 18-21, 2022 Rome – Italy. 2022;:196-197.
https://hdl.handle.net/21.15107/rcub_technorep_6682 .

Obradović, Bojana, Stojkovska, Jasmina, Radovanović, Željko, Matić, Tamara, Petrović, Rada, Janaćković, Đorđe, Veljović, Đorđe, "The ExcellMater project for advancement of novel bioceramic and composite biomaterials for medical applications" in Conference proceedings / 3rd biennial International Conference: Biomaterials and novel technologies for healthcare BIOMAH, October 18-21, 2022 Rome – Italy (2022):196-197,
https://hdl.handle.net/21.15107/rcub_technorep_6682 .

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  - Milošević, Mia
AU  - Banićević, Ivana
AU  - Pavlović, Marija
AU  - Milivojević, Milena
AU  - Stevanović, Milena
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6351
PB  - Institute of Technical Sciences of SASA
C3  - Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts
T1  - Development of a physiologically relevant osteosarcoma model based on alginate scaffolds and perfusion bioreactor
SP  - 8
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6351
ER  - 

@conference{
author = "Milošević, Mia and Banićević, Ivana and Pavlović, Marija 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 = "Development of a physiologically relevant osteosarcoma model based on alginate scaffolds and perfusion bioreactor",
pages = "8",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6351"
}

Milošević, M., Banićević, I., Pavlović, M., Milivojević, M., Stevanović, M., Stojkovska, J.,& Obradović, B.. (2022). Development of a physiologically relevant osteosarcoma 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., 8.
https://hdl.handle.net/21.15107/rcub_technorep_6351

Milošević M, Banićević I, Pavlović M, Milivojević M, Stevanović M, Stojkovska J, Obradović B. Development of a physiologically relevant osteosarcoma model based on alginate scaffolds and perfusion bioreactor. in Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts. 2022;:8.
https://hdl.handle.net/21.15107/rcub_technorep_6351 .

Milošević, Mia, Banićević, Ivana, Pavlović, Marija, Milivojević, Milena, Stevanović, Milena, Stojkovska, Jasmina, Obradović, Bojana, "Development of a physiologically relevant osteosarcoma model based on alginate scaffolds and perfusion bioreactor" in Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts (2022):8,
https://hdl.handle.net/21.15107/rcub_technorep_6351 .

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  - Menshikh, Ksenia
AU  - Banićević, Ivana
AU  - Radonjić, Mia
AU  - Miola, Marta
AU  - Stojkovska, Jasmina
AU  - Cochis, Andrea
AU  - Obradović, Bojana
AU  - Rimondini, Lia
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6216
C3  - Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts
T1  - Osteosarcoma in vitro: a step-by-step approach
SP  - 2-3
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6216
ER  - 

@conference{
author = "Menshikh, Ksenia and Banićević, Ivana and Radonjić, Mia and Miola, Marta and Stojkovska, Jasmina and Cochis, Andrea and Obradović, Bojana and Rimondini, Lia",
year = "2022",
journal = "Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts",
title = "Osteosarcoma in vitro: a step-by-step approach",
pages = "2-3",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6216"
}

Menshikh, K., Banićević, I., Radonjić, M., Miola, M., Stojkovska, J., Cochis, A., Obradović, B.,& Rimondini, L.. (2022). Osteosarcoma in vitro: a step-by-step approach. in Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts, 2-3.
https://hdl.handle.net/21.15107/rcub_technorep_6216

Menshikh K, Banićević I, Radonjić M, Miola M, Stojkovska J, Cochis A, Obradović B, Rimondini L. Osteosarcoma in vitro: a step-by-step approach. in Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts. 2022;:2-3.
https://hdl.handle.net/21.15107/rcub_technorep_6216 .

Menshikh, Ksenia, Banićević, Ivana, Radonjić, Mia, Miola, Marta, Stojkovska, Jasmina, Cochis, Andrea, Obradović, Bojana, Rimondini, Lia, "Osteosarcoma in vitro: a step-by-step approach" in Twentieth Young Researchers’ Conference - Materials Science and Engineering: Programme and the Book of Abstracts (2022):2-3,
https://hdl.handle.net/21.15107/rcub_technorep_6216 .

TY  - CONF
AU  - Zvicer, Jovana
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6958
AB  - Development of novel biomaterials for potential biomedical applications requires comprehensive preclinical studies. Traditional methods for biomaterial evaluation are based on in vitro testing routinely performed in monolayer cell cultures followed by in vivo animal studies. However, these methods have numerous limitations. Although studies in cell monolayers allow rapid evaluation of biomaterials by standardized protocols, quantitative and comparable results, cell metabolism and morphology is changed in the 2-dimensional environment often leading to unreliable results. On other hand, animal studies are complex, time-consuming, expensive and raise ethical concerns. One of the approaches to address this problem and obtain reliable results in a more efficient way is utilization of biomimetic bioreactors. These bioreactors are primarily developed as an essential component in tissue engineering mimicking physiological in vivo conditions in particular tissue or organ by providing all necessary biochemical (e.g. pH, nutrients, gases, growth factors) and biophysical signals (e.g., shear stress, hydrostatic pressure, mechanical strains) for cell differentiation and metabolic activity. Some examples include perfusion bioreactors, bioreactors with shear stresses and/or dynamic compression, and bioreactor with stretch and shear stresses imitating conditions in vascularized tissues, articular cartilage, and vascular grafts, respectively. Such physiologically relevant, while strictly controlled environment is also beneficial for biomaterial assessment, investigation of cell-biomaterial interactions, and prediction of biomaterial behaviour upon application. The present review provides readers with up-to-date studies and results regarding utilization of biomimetic bioreactors as tools for comprehensive and efficient evaluation of novel biomaterials, such as determination of mechanical characteristics, release of bioactive substances, cell-biomaterial interactions and cytotoxicity.
PB  - Belgrade : Innovation Center of Faculty of Mechanical Engineering
C3  - Programme and The Book of Abstracts / International Conference of Experimental and Numerical Investigations and New Technologies - CNN TECH 2022, 05-08 July 2022, Zlatibor, Serbia
T1  - BIOMIMETIC BIOREACTORS IN CHARACTERIZATION OF NOVEL BIOMATERIALS
SP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6958
ER  - 

@conference{
author = "Zvicer, Jovana and Stojkovska, Jasmina and Obradović, Bojana",
year = "2022",
abstract = "Development of novel biomaterials for potential biomedical applications requires comprehensive preclinical studies. Traditional methods for biomaterial evaluation are based on in vitro testing routinely performed in monolayer cell cultures followed by in vivo animal studies. However, these methods have numerous limitations. Although studies in cell monolayers allow rapid evaluation of biomaterials by standardized protocols, quantitative and comparable results, cell metabolism and morphology is changed in the 2-dimensional environment often leading to unreliable results. On other hand, animal studies are complex, time-consuming, expensive and raise ethical concerns. One of the approaches to address this problem and obtain reliable results in a more efficient way is utilization of biomimetic bioreactors. These bioreactors are primarily developed as an essential component in tissue engineering mimicking physiological in vivo conditions in particular tissue or organ by providing all necessary biochemical (e.g. pH, nutrients, gases, growth factors) and biophysical signals (e.g., shear stress, hydrostatic pressure, mechanical strains) for cell differentiation and metabolic activity. Some examples include perfusion bioreactors, bioreactors with shear stresses and/or dynamic compression, and bioreactor with stretch and shear stresses imitating conditions in vascularized tissues, articular cartilage, and vascular grafts, respectively. Such physiologically relevant, while strictly controlled environment is also beneficial for biomaterial assessment, investigation of cell-biomaterial interactions, and prediction of biomaterial behaviour upon application. The present review provides readers with up-to-date studies and results regarding utilization of biomimetic bioreactors as tools for comprehensive and efficient evaluation of novel biomaterials, such as determination of mechanical characteristics, release of bioactive substances, cell-biomaterial interactions and cytotoxicity.",
publisher = "Belgrade : Innovation Center of Faculty of Mechanical Engineering",
journal = "Programme and The Book of Abstracts / International Conference of Experimental and Numerical Investigations and New Technologies - CNN TECH 2022, 05-08 July 2022, Zlatibor, Serbia",
title = "BIOMIMETIC BIOREACTORS IN CHARACTERIZATION OF NOVEL BIOMATERIALS",
pages = "17",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6958"
}

Zvicer, J., Stojkovska, J.,& Obradović, B.. (2022). BIOMIMETIC BIOREACTORS IN CHARACTERIZATION OF NOVEL BIOMATERIALS. in Programme and The Book of Abstracts / International Conference of Experimental and Numerical Investigations and New Technologies - CNN TECH 2022, 05-08 July 2022, Zlatibor, Serbia
Belgrade : Innovation Center of Faculty of Mechanical Engineering., 17.
https://hdl.handle.net/21.15107/rcub_technorep_6958

Zvicer J, Stojkovska J, Obradović B. BIOMIMETIC BIOREACTORS IN CHARACTERIZATION OF NOVEL BIOMATERIALS. in Programme and The Book of Abstracts / International Conference of Experimental and Numerical Investigations and New Technologies - CNN TECH 2022, 05-08 July 2022, Zlatibor, Serbia. 2022;:17.
https://hdl.handle.net/21.15107/rcub_technorep_6958 .

Zvicer, Jovana, Stojkovska, Jasmina, Obradović, Bojana, "BIOMIMETIC BIOREACTORS IN CHARACTERIZATION OF NOVEL BIOMATERIALS" in Programme and The Book of Abstracts / International Conference of Experimental and Numerical Investigations and New Technologies - CNN TECH 2022, 05-08 July 2022, Zlatibor, Serbia (2022):17,
https://hdl.handle.net/21.15107/rcub_technorep_6958 .

TY  - JOUR
AU  - Dragoj, Miodrag
AU  - Stojkovska, Jasmina
AU  - Stankovic, Tijana
AU  - Dinic, Jelena
AU  - Podolski-Renic, Ana
AU  - Obradović, Bojana
AU  - Pesic, Milica
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4783
AB  - Background: Various three-dimensional (3D) glioblastoma cell culture models have a limited duration of viability. Our aim was to develop a long-term 3D glioblastoma model, which is necessary for reliable drug response studies. Methods: Human U87 glioblastoma cells were cultured in alginate microfibers for 28 days. Cell growth, viability, morphology, and aggregation in 3D culture were monitored by fluorescent and confocal microscopy upon calcein-AM/propidium iodide (CAM/PI) staining every seven days. The glioblastoma 3D model was validated using temozolomide (TMZ) treatments 3 days in a row with a recovery period. Cell viability by MTT and resistance-related gene expression (MGMT and ABCB1) by qPCR were assessed after 28 days. The same TMZ treatment schedule was applied in 2D U87 cell culture for comparison purposes. Results: Within a long-term 3D model system in alginate fibers, U87 cells remained viable for up to 28 days. On day 7, cells formed visible aggregates oriented to the microfiber periphery. TMZ treatment reduced cell growth but increased drug resistance-related gene expression. The latter effect was more pronounced in 3D compared to 2D cell culture. Conclusion: Herein, we described a long-term glioblastoma 3D model system that could be particularly helpful for drug testing and treatment optimization.
T2  - Brain Sciences
T1  - Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing
IS  - 8
VL  - 11
DO  - 10.3390/brainsci11081025
ER  - 

@article{
author = "Dragoj, Miodrag and Stojkovska, Jasmina and Stankovic, Tijana and Dinic, Jelena and Podolski-Renic, Ana and Obradović, Bojana and Pesic, Milica",
year = "2021",
abstract = "Background: Various three-dimensional (3D) glioblastoma cell culture models have a limited duration of viability. Our aim was to develop a long-term 3D glioblastoma model, which is necessary for reliable drug response studies. Methods: Human U87 glioblastoma cells were cultured in alginate microfibers for 28 days. Cell growth, viability, morphology, and aggregation in 3D culture were monitored by fluorescent and confocal microscopy upon calcein-AM/propidium iodide (CAM/PI) staining every seven days. The glioblastoma 3D model was validated using temozolomide (TMZ) treatments 3 days in a row with a recovery period. Cell viability by MTT and resistance-related gene expression (MGMT and ABCB1) by qPCR were assessed after 28 days. The same TMZ treatment schedule was applied in 2D U87 cell culture for comparison purposes. Results: Within a long-term 3D model system in alginate fibers, U87 cells remained viable for up to 28 days. On day 7, cells formed visible aggregates oriented to the microfiber periphery. TMZ treatment reduced cell growth but increased drug resistance-related gene expression. The latter effect was more pronounced in 3D compared to 2D cell culture. Conclusion: Herein, we described a long-term glioblastoma 3D model system that could be particularly helpful for drug testing and treatment optimization.",
journal = "Brain Sciences",
title = "Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing",
number = "8",
volume = "11",
doi = "10.3390/brainsci11081025"
}

Dragoj, M., Stojkovska, J., Stankovic, T., Dinic, J., Podolski-Renic, A., Obradović, B.,& Pesic, M.. (2021). Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing. in Brain Sciences, 11(8).
https://doi.org/10.3390/brainsci11081025

Dragoj M, Stojkovska J, Stankovic T, Dinic J, Podolski-Renic A, Obradović B, Pesic M. Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing. in Brain Sciences. 2021;11(8).
doi:10.3390/brainsci11081025 .

Dragoj, Miodrag, Stojkovska, Jasmina, Stankovic, Tijana, Dinic, Jelena, Podolski-Renic, Ana, Obradović, Bojana, Pesic, Milica, "Development and Validation of a Long-Term 3D Glioblastoma Cell Culture in Alginate Microfibers as a Novel Bio-Mimicking Model System for Preclinical Drug Testing" in Brain Sciences, 11, no. 8 (2021),
https://doi.org/10.3390/brainsci11081025 . .

TY  - JOUR
AU  - Stojkovska, Jasmina
AU  - Zvicer, Jovana
AU  - Andrejevic, Milica
AU  - Janaćković, Đorđe
AU  - Obradović, Bojana
AU  - Veljović, Đorđe
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4934
AB  - In the present study, we synthesized hydroxyapatite (HAP) powders followed by the production of alginate based macroporous scaffolds with the aim to imitate the natural bone structure. HAP powders were synthesized by using a hydrothermal method, and after calcination, dominant phases in the powders, undoped and doped with Mg2+ were HAP and beta-tricalcium phosphate, respectively. Upon mixing with Na-alginate, followed by gelation and freeze-dying, highly macroporous composite scaffolds were obtained with open and connected pores and uniformly dispersed mineral phase as determined by scanning electron microscopy. Mechanical properties of the scaffolds were influenced by the composition of calcium phosphate fillers being improved as Ca2+ concentration increased while Mg2+ concentration decreased. HAP formation within all scaffolds was investigated in simulated body fluid (SBF) during 28 days under static conditions while the best candidate (Mg substituted HAP filler, precursor solution with [Ca + Mg]/P molar ratio of 1.52) was investigated under more physiological conditions in a biomimetic perfusion bioreactor. The continuous SBF flow (superficial velocity of 400 mu m/s) induced the formation of abundant HAP crystals throughout the scaffolds leading to improved mechanical properties to some extent as compared to the initial scaffolds. These findings indicated potentials of novel biomimetic scaffolds for use in bone tissue engineering.
T2  - Journal of Biomedical Materials Research Part B-Applied Biomaterials
T1  - Novel composite scaffolds based on alginate and Mg-doped calcium phosphate fillers: Enhanced hydroxyapatite formation under biomimetic conditions
EP  - 2090
IS  - 12
SP  - 2079
VL  - 109
DO  - 10.1002/jbm.b.34856
ER  - 

@article{
author = "Stojkovska, Jasmina and Zvicer, Jovana and Andrejevic, Milica and Janaćković, Đorđe and Obradović, Bojana and Veljović, Đorđe",
year = "2021",
abstract = "In the present study, we synthesized hydroxyapatite (HAP) powders followed by the production of alginate based macroporous scaffolds with the aim to imitate the natural bone structure. HAP powders were synthesized by using a hydrothermal method, and after calcination, dominant phases in the powders, undoped and doped with Mg2+ were HAP and beta-tricalcium phosphate, respectively. Upon mixing with Na-alginate, followed by gelation and freeze-dying, highly macroporous composite scaffolds were obtained with open and connected pores and uniformly dispersed mineral phase as determined by scanning electron microscopy. Mechanical properties of the scaffolds were influenced by the composition of calcium phosphate fillers being improved as Ca2+ concentration increased while Mg2+ concentration decreased. HAP formation within all scaffolds was investigated in simulated body fluid (SBF) during 28 days under static conditions while the best candidate (Mg substituted HAP filler, precursor solution with [Ca + Mg]/P molar ratio of 1.52) was investigated under more physiological conditions in a biomimetic perfusion bioreactor. The continuous SBF flow (superficial velocity of 400 mu m/s) induced the formation of abundant HAP crystals throughout the scaffolds leading to improved mechanical properties to some extent as compared to the initial scaffolds. These findings indicated potentials of novel biomimetic scaffolds for use in bone tissue engineering.",
journal = "Journal of Biomedical Materials Research Part B-Applied Biomaterials",
title = "Novel composite scaffolds based on alginate and Mg-doped calcium phosphate fillers: Enhanced hydroxyapatite formation under biomimetic conditions",
pages = "2090-2079",
number = "12",
volume = "109",
doi = "10.1002/jbm.b.34856"
}

Stojkovska, J., Zvicer, J., Andrejevic, M., Janaćković, Đ., Obradović, B.,& Veljović, Đ.. (2021). Novel composite scaffolds based on alginate and Mg-doped calcium phosphate fillers: Enhanced hydroxyapatite formation under biomimetic conditions. in Journal of Biomedical Materials Research Part B-Applied Biomaterials, 109(12), 2079-2090.
https://doi.org/10.1002/jbm.b.34856

Stojkovska J, Zvicer J, Andrejevic M, Janaćković Đ, Obradović B, Veljović Đ. Novel composite scaffolds based on alginate and Mg-doped calcium phosphate fillers: Enhanced hydroxyapatite formation under biomimetic conditions. in Journal of Biomedical Materials Research Part B-Applied Biomaterials. 2021;109(12):2079-2090.
doi:10.1002/jbm.b.34856 .

Stojkovska, Jasmina, Zvicer, Jovana, Andrejevic, Milica, Janaćković, Đorđe, Obradović, Bojana, Veljović, Đorđe, "Novel composite scaffolds based on alginate and Mg-doped calcium phosphate fillers: Enhanced hydroxyapatite formation under biomimetic conditions" in Journal of Biomedical Materials Research Part B-Applied Biomaterials, 109, no. 12 (2021):2079-2090,
https://doi.org/10.1002/jbm.b.34856 . .

TY  - CONF
AU  - Banićević, Ivana
AU  - Radonjić, Mia
AU  - Pavlović, Marija
AU  - Milivojević, Milena
AU  - Stevanović, Milena
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5028
AB  - Osteosarcoma is the most common type of bone cancer, which affects both children and
adults. Treatment of osteosarcoma exhibits slow progress due to inadequacy of both in vivo
animal models and 2D in vitro models regularly used for antitumor drug testing. Our
approach is to create a physiologically relevant 3D in vitro model for osteosarcoma cell
cultivation, which has the potential to overcome inherent weaknesses of 2D in vitro and
animal models. In order to imitate native osteosarcoma microenvironment, macroporous
alginate scaffolds with incorporated hydroxyapatite/β-tricalcium phosphate (HAp/β-TCP)
powder were produced with two compositions: 1 wt% alginate, 1 wt% powder and 2 wt.%
alginate, 2 wt% powder. Bioactivity and stability of the scaffolds were investigated under
biomimetic conditions of continuous flow of the culture medium in perfusion bioreactor at
the superficial medium velocity of 400 µm/s, which was reported in literature to be
beneficial for osteogenesis. Scaffolds with the higher alginate concentration was shown to be
more stable in the culture medium, since the scaffolds with the lower alginate concentration
disintegrated after 5-7 days under flow conditions. Biocompatibility of the obtained scaffolds
was investigated in short-term cultivation studies of murine osteosarcoma cells K7M2-wt
seeded onto the scaffolds. The scaffolds were cultivated in perfusion bioreactors at the
superficial flow velocity of 15 µm/s, while static cultures served as a control. After
cultivation, osteosarcoma cells remained adhered to the scaffold surface, expressed
metabolic activity and retained their initial proliferation ability while the flow was shown to
positively affect the cultivated cells.
PB  - Institute of Technical Sciences of SASA
C3  - Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts
T1  - Development of a physiologically relevant 3D in vitro model for osteosarcoma cell cultivation comprising alginate composite scaffolds and a perfusion bioreactor system
SP  - 6
VL  - 17
UR  - https://hdl.handle.net/21.15107/rcub_technorep_5028
ER  - 

@conference{
author = "Banićević, Ivana and Radonjić, Mia and Pavlović, Marija and Milivojević, Milena and Stevanović, Milena and Stojkovska, Jasmina and Obradović, Bojana",
year = "2021",
abstract = "Osteosarcoma is the most common type of bone cancer, which affects both children and
adults. Treatment of osteosarcoma exhibits slow progress due to inadequacy of both in vivo
animal models and 2D in vitro models regularly used for antitumor drug testing. Our
approach is to create a physiologically relevant 3D in vitro model for osteosarcoma cell
cultivation, which has the potential to overcome inherent weaknesses of 2D in vitro and
animal models. In order to imitate native osteosarcoma microenvironment, macroporous
alginate scaffolds with incorporated hydroxyapatite/β-tricalcium phosphate (HAp/β-TCP)
powder were produced with two compositions: 1 wt% alginate, 1 wt% powder and 2 wt.%
alginate, 2 wt% powder. Bioactivity and stability of the scaffolds were investigated under
biomimetic conditions of continuous flow of the culture medium in perfusion bioreactor at
the superficial medium velocity of 400 µm/s, which was reported in literature to be
beneficial for osteogenesis. Scaffolds with the higher alginate concentration was shown to be
more stable in the culture medium, since the scaffolds with the lower alginate concentration
disintegrated after 5-7 days under flow conditions. Biocompatibility of the obtained scaffolds
was investigated in short-term cultivation studies of murine osteosarcoma cells K7M2-wt
seeded onto the scaffolds. The scaffolds were cultivated in perfusion bioreactors at the
superficial flow velocity of 15 µm/s, while static cultures served as a control. After
cultivation, osteosarcoma cells remained adhered to the scaffold surface, expressed
metabolic activity and retained their initial proliferation ability while the flow was shown to
positively affect the cultivated cells.",
publisher = "Institute of Technical Sciences of SASA",
journal = "Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts",
title = "Development of a physiologically relevant 3D in vitro model for osteosarcoma cell cultivation comprising alginate composite scaffolds and a perfusion bioreactor system",
pages = "6",
volume = "17",
url = "https://hdl.handle.net/21.15107/rcub_technorep_5028"
}

Banićević, I., Radonjić, M., Pavlović, M., Milivojević, M., Stevanović, M., Stojkovska, J.,& Obradović, B.. (2021). Development of a physiologically relevant 3D in vitro model for osteosarcoma cell cultivation comprising alginate composite scaffolds and a perfusion bioreactor system. in Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts
Institute of Technical Sciences of SASA., 17, 6.
https://hdl.handle.net/21.15107/rcub_technorep_5028

Banićević I, Radonjić M, Pavlović M, Milivojević M, Stevanović M, Stojkovska J, Obradović B. Development of a physiologically relevant 3D in vitro model for osteosarcoma cell cultivation comprising alginate composite scaffolds and a perfusion bioreactor system. in Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts. 2021;17:6.
https://hdl.handle.net/21.15107/rcub_technorep_5028 .

Banićević, Ivana, Radonjić, Mia, Pavlović, Marija, Milivojević, Milena, Stevanović, Milena, Stojkovska, Jasmina, Obradović, Bojana, "Development of a physiologically relevant 3D in vitro model for osteosarcoma cell cultivation comprising alginate composite scaffolds and a perfusion bioreactor system" in Nineteenth Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts, 17 (2021):6,
https://hdl.handle.net/21.15107/rcub_technorep_5028 .

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  - Radonjić, Mia
AU  - Petrović, Jelena
AU  - Milivojević, Milena
AU  - Stevanović, Milena
AU  - Stojkovska, Jasmina
AU  - Obradović, Bojana
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6354
AB  - Cancer cell immobilization in polymer hydrogels serving as extracellular matrices and cultivation in perfusion bioreactors
that provide appropriate chemical signals, efficient mass transfer and hydrodynamic shear stresses is a promising strategy
for development of physiologically relevant tumor models. In this work, perfusion cultures of 2 cancer cell types (C6 rat
glioma and embryonal carcinoma NT2/D1 cells) immobilized in alginate microgels were established, while static cultures
served as controls. Continuous perfusion had different effects on the cultured cells inducing enhanced proliferation of the
glioma cells immobilized in microfibers (8x10^6 cell/ml), while reducing the viability of the NT2/D1 cells immobilized in
microbeads (1x10^6 cell/ml). In order to elucidate the observed effects, chemical engineering principles were applied to
assess mass transfer and hydrodynamic conditions. The second Fick’s law was solved analytically while the diffusionadvection-reaction equation was solved numerically to model mass transport in the static and bioreactor cultures,
respectively. Moreover, Reynolds numbers, pressure drops and shear stresses in bioreactor cultures were calculated for
assessment of flow regime and hydrodynamic conditions. The modeling results have indicated that oxygen transport is
diffusion-controlled through the alginate hydrogel, while medium perfusion improves mass transfer of larger compounds
having smaller diffusion coefficients (∼10^(-13) m^2/s), which possibly stimulated glioma cell proliferation. On the other
hand, the obtained shear stress (~50 mPa) in the perfused packed bed of microbeads was above physiological levels, which
provided the explanation of the poor NT2/D1 cell survival. This study stresses the importance of multidisciplinary approach
in addressing such multifactorial diseases as cancer.
C3  - 6th World TERMIS Conference 2021 Abstract Book
T1  - Optimization of 3D cancer cell culture conditions by application of chemical engineering principles
SP  - 1408
UR  - https://hdl.handle.net/21.15107/rcub_technorep_6354
ER  - 

@conference{
author = "Radonjić, Mia and Petrović, Jelena and Milivojević, Milena and Stevanović, Milena and Stojkovska, Jasmina and Obradović, Bojana",
year = "2021",
abstract = "Cancer cell immobilization in polymer hydrogels serving as extracellular matrices and cultivation in perfusion bioreactors
that provide appropriate chemical signals, efficient mass transfer and hydrodynamic shear stresses is a promising strategy
for development of physiologically relevant tumor models. In this work, perfusion cultures of 2 cancer cell types (C6 rat
glioma and embryonal carcinoma NT2/D1 cells) immobilized in alginate microgels were established, while static cultures
served as controls. Continuous perfusion had different effects on the cultured cells inducing enhanced proliferation of the
glioma cells immobilized in microfibers (8x10^6 cell/ml), while reducing the viability of the NT2/D1 cells immobilized in
microbeads (1x10^6 cell/ml). In order to elucidate the observed effects, chemical engineering principles were applied to
assess mass transfer and hydrodynamic conditions. The second Fick’s law was solved analytically while the diffusionadvection-reaction equation was solved numerically to model mass transport in the static and bioreactor cultures,
respectively. Moreover, Reynolds numbers, pressure drops and shear stresses in bioreactor cultures were calculated for
assessment of flow regime and hydrodynamic conditions. The modeling results have indicated that oxygen transport is
diffusion-controlled through the alginate hydrogel, while medium perfusion improves mass transfer of larger compounds
having smaller diffusion coefficients (∼10^(-13) m^2/s), which possibly stimulated glioma cell proliferation. On the other
hand, the obtained shear stress (~50 mPa) in the perfused packed bed of microbeads was above physiological levels, which
provided the explanation of the poor NT2/D1 cell survival. This study stresses the importance of multidisciplinary approach
in addressing such multifactorial diseases as cancer.",
journal = "6th World TERMIS Conference 2021 Abstract Book",
title = "Optimization of 3D cancer cell culture conditions by application of chemical engineering principles",
pages = "1408",
url = "https://hdl.handle.net/21.15107/rcub_technorep_6354"
}

Radonjić, M., Petrović, J., Milivojević, M., Stevanović, M., Stojkovska, J.,& Obradović, B.. (2021). Optimization of 3D cancer cell culture conditions by application of chemical engineering principles. in 6th World TERMIS Conference 2021 Abstract Book, 1408.
https://hdl.handle.net/21.15107/rcub_technorep_6354

Radonjić M, Petrović J, Milivojević M, Stevanović M, Stojkovska J, Obradović B. Optimization of 3D cancer cell culture conditions by application of chemical engineering principles. in 6th World TERMIS Conference 2021 Abstract Book. 2021;:1408.
https://hdl.handle.net/21.15107/rcub_technorep_6354 .

Radonjić, Mia, Petrović, Jelena, Milivojević, Milena, Stevanović, Milena, Stojkovska, Jasmina, Obradović, Bojana, "Optimization of 3D cancer cell culture conditions by application of chemical engineering principles" in 6th World TERMIS Conference 2021 Abstract Book (2021):1408,
https://hdl.handle.net/21.15107/rcub_technorep_6354 .

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 .

TY  - JOUR
AU  - Stojkovska, Jasmina
AU  - Zvicer, Jovana
AU  - Milivojević, Milena
AU  - Petrović, Isidora
AU  - Stevanović, Milena
AU  - Obradović, Bojana
PY  - 2020
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4373
AB  - Development of drugs is a complex, time- and cost-consuming process due to the lack of standardized and reliable characterization techniques and models. Traditionally, drug screening is based on in vitro analysis using two-dimensional (2D) cell cultures followed by in vivo animal testing. Unfortunately, application of the obtained results to humans in about 90 % of cases fails. Therefore, it is important to develop and improve cell-based systems that can mimic the in vivo-like conditions to provide more reliable results. In this paper, we present development and validation of a novel, user-friendly perfusion bioreactor system for single use aimed for cancer research, drug screening, anti-cancer drug response studies, biomaterial characterization, and tissue engineering. Simple design of the perfusion bioreactor provides direct medium flow at physiological velocities (100-250 mu m s(-1)) through samples of different sizes and shapes. Biocompatibility of the bioreactor was confirmed in short term cultivation studies of cervical carcinoma SiHa cells immobilized in alginate microfibers under continuous medium flow. The results have shown preserved cell viability indicating that the perfusion bioreactor in conjunction with alginate hydrogels as cell carriers could be potentially used as a tool for controlled anti-cancer drug screening in a 3D environment.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska industrija
T1  - Validation of a novel perfusion bioreactor system in cancer research
EP  - 196
IS  - 3
SP  - 187
VL  - 74
DO  - 10.2298/HEMIND200329015S
ER  - 

@article{
author = "Stojkovska, Jasmina and Zvicer, Jovana and Milivojević, Milena and Petrović, Isidora and Stevanović, Milena and Obradović, Bojana",
year = "2020",
abstract = "Development of drugs is a complex, time- and cost-consuming process due to the lack of standardized and reliable characterization techniques and models. Traditionally, drug screening is based on in vitro analysis using two-dimensional (2D) cell cultures followed by in vivo animal testing. Unfortunately, application of the obtained results to humans in about 90 % of cases fails. Therefore, it is important to develop and improve cell-based systems that can mimic the in vivo-like conditions to provide more reliable results. In this paper, we present development and validation of a novel, user-friendly perfusion bioreactor system for single use aimed for cancer research, drug screening, anti-cancer drug response studies, biomaterial characterization, and tissue engineering. Simple design of the perfusion bioreactor provides direct medium flow at physiological velocities (100-250 mu m s(-1)) through samples of different sizes and shapes. Biocompatibility of the bioreactor was confirmed in short term cultivation studies of cervical carcinoma SiHa cells immobilized in alginate microfibers under continuous medium flow. The results have shown preserved cell viability indicating that the perfusion bioreactor in conjunction with alginate hydrogels as cell carriers could be potentially used as a tool for controlled anti-cancer drug screening in a 3D environment.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska industrija",
title = "Validation of a novel perfusion bioreactor system in cancer research",
pages = "196-187",
number = "3",
volume = "74",
doi = "10.2298/HEMIND200329015S"
}

Stojkovska, J., Zvicer, J., Milivojević, M., Petrović, I., Stevanović, M.,& Obradović, B.. (2020). Validation of a novel perfusion bioreactor system in cancer research. in Hemijska industrija
Savez hemijskih inženjera, Beograd., 74(3), 187-196.
https://doi.org/10.2298/HEMIND200329015S

Stojkovska J, Zvicer J, Milivojević M, Petrović I, Stevanović M, Obradović B. Validation of a novel perfusion bioreactor system in cancer research. in Hemijska industrija. 2020;74(3):187-196.
doi:10.2298/HEMIND200329015S .

Stojkovska, Jasmina, Zvicer, Jovana, Milivojević, Milena, Petrović, Isidora, Stevanović, Milena, Obradović, Bojana, "Validation of a novel perfusion bioreactor system in cancer research" in Hemijska industrija, 74, no. 3 (2020):187-196,
https://doi.org/10.2298/HEMIND200329015S . .

TY  - JOUR
AU  - Stojkovska, Jasmina
AU  - Zvicer, Jovana
AU  - Obradović, Bojana
PY  - 2020
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4451
AB  - Nanocomposite hydrogels that contain silver nanoparticles (AgNPs) are especially attractive for various biomedical applications (e.g., antimicrobial wound dressings, coatings and soft tissue implants) due to strong antimicrobial activity of released silver nanoparticles and/or ions over prolonged times. However, all potential biomedical products have to be thoroughly specified fulfilling strict safety requirements. Characterization of nanocomposites is additionally complicated due to potential harmful effects of nanoparticles and accumulation in cells and tissues. This paper summarizes methods for preclinical characterization of hydrogel nanocomposites containing AgNPs with the particular attention on Ag/alginate hydrogels. Standard physicochemical characterization methods include transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR). Functional in vitro characterization relies on different methods for estimation of silver release, antimicrobial activity, and nanocomposite cytotoxicity. Here, we specially focus on utilization of 3D bioreactor systems that mimic native physiological environments with the aim to reliably predict nanocomposite behavior during implementation and so to decrease the need for animal experimentation. These systems were shown to provide more accurate and relevant data on silver release and cytotoxicity as compared to static systems such as 2D cell monolayer cultures. Finally, nanocomposites are evaluated in vivo in different animal models, which are in the case of wound dressings typically mice, rats, and pigs. The present review provides a basis for defining a strategy for comprehensive and efficient preclinical characterization of novel nanocomposites attractive not only for those containing AgNPs but also other metallic nanoparticles aimed for biomedical applications. Key points center dot A platform for devising comprehensive preclinical evaluation of nanocomposites. center dot Biomimetic bioreactors provide reliable functional nanocomposite evaluation. center dot Cells in 2D cultures are more sensitive to silver nanoparticles than in 3D cultures. center dot Biomimetic bioreactor 3D cell/tissue cultures can address the in vitro-in vivo gap.
PB  - Springer, New York
T2  - Applied Microbiology and Biotechnology
T1  - Preclinical functional characterization methods of nanocomposite hydrogels containing silver nanoparticles for biomedical applications
EP  - 4658
IS  - 11
SP  - 4643
VL  - 104
DO  - 10.1007/s00253-020-10521-2
ER  - 

@article{
author = "Stojkovska, Jasmina and Zvicer, Jovana and Obradović, Bojana",
year = "2020",
abstract = "Nanocomposite hydrogels that contain silver nanoparticles (AgNPs) are especially attractive for various biomedical applications (e.g., antimicrobial wound dressings, coatings and soft tissue implants) due to strong antimicrobial activity of released silver nanoparticles and/or ions over prolonged times. However, all potential biomedical products have to be thoroughly specified fulfilling strict safety requirements. Characterization of nanocomposites is additionally complicated due to potential harmful effects of nanoparticles and accumulation in cells and tissues. This paper summarizes methods for preclinical characterization of hydrogel nanocomposites containing AgNPs with the particular attention on Ag/alginate hydrogels. Standard physicochemical characterization methods include transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR). Functional in vitro characterization relies on different methods for estimation of silver release, antimicrobial activity, and nanocomposite cytotoxicity. Here, we specially focus on utilization of 3D bioreactor systems that mimic native physiological environments with the aim to reliably predict nanocomposite behavior during implementation and so to decrease the need for animal experimentation. These systems were shown to provide more accurate and relevant data on silver release and cytotoxicity as compared to static systems such as 2D cell monolayer cultures. Finally, nanocomposites are evaluated in vivo in different animal models, which are in the case of wound dressings typically mice, rats, and pigs. The present review provides a basis for defining a strategy for comprehensive and efficient preclinical characterization of novel nanocomposites attractive not only for those containing AgNPs but also other metallic nanoparticles aimed for biomedical applications. Key points center dot A platform for devising comprehensive preclinical evaluation of nanocomposites. center dot Biomimetic bioreactors provide reliable functional nanocomposite evaluation. center dot Cells in 2D cultures are more sensitive to silver nanoparticles than in 3D cultures. center dot Biomimetic bioreactor 3D cell/tissue cultures can address the in vitro-in vivo gap.",
publisher = "Springer, New York",
journal = "Applied Microbiology and Biotechnology",
title = "Preclinical functional characterization methods of nanocomposite hydrogels containing silver nanoparticles for biomedical applications",
pages = "4658-4643",
number = "11",
volume = "104",
doi = "10.1007/s00253-020-10521-2"
}

Stojkovska, J., Zvicer, J.,& Obradović, B.. (2020). Preclinical functional characterization methods of nanocomposite hydrogels containing silver nanoparticles for biomedical applications. in Applied Microbiology and Biotechnology
Springer, New York., 104(11), 4643-4658.
https://doi.org/10.1007/s00253-020-10521-2

Stojkovska J, Zvicer J, Obradović B. Preclinical functional characterization methods of nanocomposite hydrogels containing silver nanoparticles for biomedical applications. in Applied Microbiology and Biotechnology. 2020;104(11):4643-4658.
doi:10.1007/s00253-020-10521-2 .

Stojkovska, Jasmina, Zvicer, Jovana, Obradović, Bojana, "Preclinical functional characterization methods of nanocomposite hydrogels containing silver nanoparticles for biomedical applications" in Applied Microbiology and Biotechnology, 104, no. 11 (2020):4643-4658,
https://doi.org/10.1007/s00253-020-10521-2 . .

TY  - JOUR
AU  - Stojkovska, Jasmina
AU  - Petrović, Predrag
AU  - Jancić, Ivan
AU  - Milenković, Marina
AU  - Obradović, Bojana
PY  - 2019
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4043
AB  - Novel alginate hydrogels with silver nanoparticles (AgNPs) and honey components were produced with the aim to target multidrug-resistant bacterial strains causing nosocomial wound infections. AgNP synthesis was optimized in highly concentrated honey solutions so that a 5-month stable, colloid solution with 50% of honey and similar to 8 nm AgNPs at neutral pH was obtained. The colloid solution was further used to produce nano-composite Ag/alginate hydrogels in different forms (microbeads, microfibers and discs) that retained all AgNPs and high fractions of honey components (40-60%) as determined by the phenol-sulfuric acid and Folin-Ciocalteu methods. The hydrogels were characterized by UV-Vis spectroscopy and Fourier-transform infrared-attenuated total reflectance spectroscopy while the antibacterial activity was investigated against a broad spectrum of Gram-negative and Gram-positive bacteria, including 13 multi-resistant clinical strains of Acinetobacter baumannii, one clinical strain of Pseudomonas aeruginosa and one clinical strain of Staphylococcus aureus. At the total released silver concentration of similar to 9 mu g/ml, the hydrogels exhibited strong bactericidal activity against standard and most of the investigated multi-resistant hospital strains with the exemption of 3 clinical strains of A. baumannii in which antibacterial effects were absent. These results reveal the need for further in-depth studies of bacterial resistance mechanisms and, in the same time, potentials of the novel Ag/alginate hydrogels with honey components to combat wound infections and enhance healing as non-sticky, antibacterial, and bioactive dressings.
PB  - Springer, New York
T2  - Applied Microbiology and Biotechnology
T1  - Novel nano-composite hydrogels with honey effective against multi-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa
EP  - 8543
IS  - 20
SP  - 8529
VL  - 103
DO  - 10.1007/s00253-019-10055-2
ER  - 

@article{
author = "Stojkovska, Jasmina and Petrović, Predrag and Jancić, Ivan and Milenković, Marina and Obradović, Bojana",
year = "2019",
abstract = "Novel alginate hydrogels with silver nanoparticles (AgNPs) and honey components were produced with the aim to target multidrug-resistant bacterial strains causing nosocomial wound infections. AgNP synthesis was optimized in highly concentrated honey solutions so that a 5-month stable, colloid solution with 50% of honey and similar to 8 nm AgNPs at neutral pH was obtained. The colloid solution was further used to produce nano-composite Ag/alginate hydrogels in different forms (microbeads, microfibers and discs) that retained all AgNPs and high fractions of honey components (40-60%) as determined by the phenol-sulfuric acid and Folin-Ciocalteu methods. The hydrogels were characterized by UV-Vis spectroscopy and Fourier-transform infrared-attenuated total reflectance spectroscopy while the antibacterial activity was investigated against a broad spectrum of Gram-negative and Gram-positive bacteria, including 13 multi-resistant clinical strains of Acinetobacter baumannii, one clinical strain of Pseudomonas aeruginosa and one clinical strain of Staphylococcus aureus. At the total released silver concentration of similar to 9 mu g/ml, the hydrogels exhibited strong bactericidal activity against standard and most of the investigated multi-resistant hospital strains with the exemption of 3 clinical strains of A. baumannii in which antibacterial effects were absent. These results reveal the need for further in-depth studies of bacterial resistance mechanisms and, in the same time, potentials of the novel Ag/alginate hydrogels with honey components to combat wound infections and enhance healing as non-sticky, antibacterial, and bioactive dressings.",
publisher = "Springer, New York",
journal = "Applied Microbiology and Biotechnology",
title = "Novel nano-composite hydrogels with honey effective against multi-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa",
pages = "8543-8529",
number = "20",
volume = "103",
doi = "10.1007/s00253-019-10055-2"
}

Stojkovska, J., Petrović, P., Jancić, I., Milenković, M.,& Obradović, B.. (2019). Novel nano-composite hydrogels with honey effective against multi-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa. in Applied Microbiology and Biotechnology
Springer, New York., 103(20), 8529-8543.
https://doi.org/10.1007/s00253-019-10055-2

Stojkovska J, Petrović P, Jancić I, Milenković M, Obradović B. Novel nano-composite hydrogels with honey effective against multi-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa. in Applied Microbiology and Biotechnology. 2019;103(20):8529-8543.
doi:10.1007/s00253-019-10055-2 .

Stojkovska, Jasmina, Petrović, Predrag, Jancić, Ivan, Milenković, Marina, Obradović, Bojana, "Novel nano-composite hydrogels with honey effective against multi-resistant clinical strains of Acinetobacter baumannii and Pseudomonas aeruginosa" in Applied Microbiology and Biotechnology, 103, no. 20 (2019):8529-8543,
https://doi.org/10.1007/s00253-019-10055-2 . .

TY  - JOUR
AU  - Kaczmarek, B.
AU  - Sionkowska, A.
AU  - Stojkovska, Jasmina
PY  - 2018
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/3866
AB  - Scaffolds based on chitosan (CTS), collagen (Coll), and glycosaminoglycans (GAGs) cross-linked by sodium alginate (SA) were obtained with the use of the freeze-drying method. They were characterized by different analyses, e.g. infrared spectroscopy, SEM images and differential scanning calorimetry. Furthermore, bio-mechanical properties of the scaffolds were determined in a biomimetic bioreactor. The results showed that the scaffolds based on chitosan, collagen, and glycosaminoglycans cross-linked by sodium alginate are stable in aqueous environment. The infrared spectroscopy analysis showed the hydrogen bond formation between polymers. Scaffolds presented open-pores structures even after a 3-day long analysis in a perfusion bioreactor. The obtained results indicate that the addition of sodium alginate slightly modified biomechanical properties.
PB  - Elsevier Sci Ltd, Oxford
T2  - Polymer Testing
T1  - Characterization of scaffolds based on chitosan and collagen with glycosaminoglycans and sodium alginate addition
EP  - 232
SP  - 229
VL  - 68
DO  - 10.1016/j.polymertesting.2018.04.021
ER  - 

@article{
author = "Kaczmarek, B. and Sionkowska, A. and Stojkovska, Jasmina",
year = "2018",
abstract = "Scaffolds based on chitosan (CTS), collagen (Coll), and glycosaminoglycans (GAGs) cross-linked by sodium alginate (SA) were obtained with the use of the freeze-drying method. They were characterized by different analyses, e.g. infrared spectroscopy, SEM images and differential scanning calorimetry. Furthermore, bio-mechanical properties of the scaffolds were determined in a biomimetic bioreactor. The results showed that the scaffolds based on chitosan, collagen, and glycosaminoglycans cross-linked by sodium alginate are stable in aqueous environment. The infrared spectroscopy analysis showed the hydrogen bond formation between polymers. Scaffolds presented open-pores structures even after a 3-day long analysis in a perfusion bioreactor. The obtained results indicate that the addition of sodium alginate slightly modified biomechanical properties.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Polymer Testing",
title = "Characterization of scaffolds based on chitosan and collagen with glycosaminoglycans and sodium alginate addition",
pages = "232-229",
volume = "68",
doi = "10.1016/j.polymertesting.2018.04.021"
}

Kaczmarek, B., Sionkowska, A.,& Stojkovska, J.. (2018). Characterization of scaffolds based on chitosan and collagen with glycosaminoglycans and sodium alginate addition. in Polymer Testing
Elsevier Sci Ltd, Oxford., 68, 229-232.
https://doi.org/10.1016/j.polymertesting.2018.04.021

Kaczmarek B, Sionkowska A, Stojkovska J. Characterization of scaffolds based on chitosan and collagen with glycosaminoglycans and sodium alginate addition. in Polymer Testing. 2018;68:229-232.
doi:10.1016/j.polymertesting.2018.04.021 .

Kaczmarek, B., Sionkowska, A., Stojkovska, Jasmina, "Characterization of scaffolds based on chitosan and collagen with glycosaminoglycans and sodium alginate addition" in Polymer Testing, 68 (2018):229-232,
https://doi.org/10.1016/j.polymertesting.2018.04.021 . .

TY  - JOUR
AU  - Stojkovska, Jasmina
AU  - Đurđević, Željka
AU  - Jančić, Ivan
AU  - Bufan, Biljana
AU  - Milenković, Marina
AU  - Janković, Radmila
AU  - Mišković-Stanković, Vesna
AU  - Obradović, Bojana
PY  - 2018
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4021
AB  - In the present study, possibilities for using novel nanocomposites based on alginate and silver nanoparticles for wound treatment were investigated in a second-degree thermal burn model in Wistar rats. Silver nanoparticles (AgNPs) were electrochemically synthesized in alginate solutions that were further utilized to obtain the Ag/alginate solution and microfibers for subsequent in vivo studies. Daily applications of the Ag/alginate colloid solution, containing AgNPs, alginate and ascorbic acid (G3), wet Ag/alginate microfibers containing AgNPs (G5) and dry Ag/alginate microfibers containing AgNPs (G6) were compared to treatments with a commercial cream containing silver sulfadiazine (G2) and a commercial Ca-alginate wound dressing containing silver ions (G4), as well as to the untreated controls (G1). Results of the in vivo study have shown faster healing in treated wounds, which completely healed on day 19 (G4, G5 and G6) and 21 (G2 and G3) after the thermal injury, while the period for complete reepitelization of untreated wounds (G1) was 25 days. The macroscopic analysis has shown that scabs fell off between day 10 and 12 after the thermal injury induction in treated groups, whereas between day 15 and 16 in the control group. These macroscopic findings were supported by the results of histopathological analyses, which have shown enhanced granulation and reepithelization, reduced inflammation and improved organization of the extracellular matrix in treated groups without adverse effects. Among the treated groups, dressings based on Ca-alginate (G4-G6) induced enhanced healing as compared to the other two groups (G2, G3), which could be attributed to additional stimuli of released Ca2+. The obtained results indicated potentials of novel nanocomposites based on alginate and AgNPs for therapeutic applications in wound treatments.
PB  - Sage Publications Ltd, London
T2  - Journal of Biomaterials Applications
T1  - Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments
EP  - 1211
IS  - 9
SP  - 1197
VL  - 32
DO  - 10.1177/0885328218759564
ER  - 

@article{
author = "Stojkovska, Jasmina and Đurđević, Željka and Jančić, Ivan and Bufan, Biljana and Milenković, Marina and Janković, Radmila and Mišković-Stanković, Vesna and Obradović, Bojana",
year = "2018",
abstract = "In the present study, possibilities for using novel nanocomposites based on alginate and silver nanoparticles for wound treatment were investigated in a second-degree thermal burn model in Wistar rats. Silver nanoparticles (AgNPs) were electrochemically synthesized in alginate solutions that were further utilized to obtain the Ag/alginate solution and microfibers for subsequent in vivo studies. Daily applications of the Ag/alginate colloid solution, containing AgNPs, alginate and ascorbic acid (G3), wet Ag/alginate microfibers containing AgNPs (G5) and dry Ag/alginate microfibers containing AgNPs (G6) were compared to treatments with a commercial cream containing silver sulfadiazine (G2) and a commercial Ca-alginate wound dressing containing silver ions (G4), as well as to the untreated controls (G1). Results of the in vivo study have shown faster healing in treated wounds, which completely healed on day 19 (G4, G5 and G6) and 21 (G2 and G3) after the thermal injury, while the period for complete reepitelization of untreated wounds (G1) was 25 days. The macroscopic analysis has shown that scabs fell off between day 10 and 12 after the thermal injury induction in treated groups, whereas between day 15 and 16 in the control group. These macroscopic findings were supported by the results of histopathological analyses, which have shown enhanced granulation and reepithelization, reduced inflammation and improved organization of the extracellular matrix in treated groups without adverse effects. Among the treated groups, dressings based on Ca-alginate (G4-G6) induced enhanced healing as compared to the other two groups (G2, G3), which could be attributed to additional stimuli of released Ca2+. The obtained results indicated potentials of novel nanocomposites based on alginate and AgNPs for therapeutic applications in wound treatments.",
publisher = "Sage Publications Ltd, London",
journal = "Journal of Biomaterials Applications",
title = "Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments",
pages = "1211-1197",
number = "9",
volume = "32",
doi = "10.1177/0885328218759564"
}

Stojkovska, J., Đurđević, Ž., Jančić, I., Bufan, B., Milenković, M., Janković, R., Mišković-Stanković, V.,& Obradović, B.. (2018). Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments. in Journal of Biomaterials Applications
Sage Publications Ltd, London., 32(9), 1197-1211.
https://doi.org/10.1177/0885328218759564

Stojkovska J, Đurđević Ž, Jančić I, Bufan B, Milenković M, Janković R, Mišković-Stanković V, Obradović B. Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments. in Journal of Biomaterials Applications. 2018;32(9):1197-1211.
doi:10.1177/0885328218759564 .

Stojkovska, Jasmina, Đurđević, Željka, Jančić, Ivan, Bufan, Biljana, Milenković, Marina, Janković, Radmila, Mišković-Stanković, Vesna, Obradović, Bojana, "Comparative in vivo evaluation of novel formulations based on alginate and silver nanoparticles for wound treatments" in Journal of Biomaterials Applications, 32, no. 9 (2018):1197-1211,
https://doi.org/10.1177/0885328218759564 . .

TY  - THES
AU  - Stojkovska, Jasmina
PY  - 2015
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=3174
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:11520/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=47506447
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4626
AB  - Development of novel nanocomposite biomaterials for biomedical applications requires comprehensive evaluation and characterization of biomaterials such as determination of the chemical composition, physical properties, biocompatibility and functionality. In addition, successful development of biomaterials for potential biomedical applications requires all inclusive association of all the results for reliable prediction of the behavior and functionality of biomaterials in the desired application. The aim of this doctoral thesis was to investigate possibilities for production of antimicrobial hydrogels in different forms from alginate colloid solutions with electrochemically synthesized silver nanoparticles, as well as comprehensive evaluation of the obtained nanocomposits under in vitro and in vivo conditions. In vitro studies included assessment of cytotoxicity, biomechanical properties, antimicrobial activity and silver release, while in vivo studies comprised functionality evaluation of the nanocomposites for potential biomedical applications in wound tretman...
AB  - Razvoj novih nanokompozitnih biomaterijala za biomedicinsku primenu zahteva različita ispitivanja i karakterisanje biomaterijala kako sa stanovišta hemijskog sastava i fizičkih svojstava, tako i sa stanovišta biokompatibilnosti i funkcionalnosti. Uz to, da bi se razvio optimizovan biomaterijal potrebno je rezultate svih ispitivanja povezati i objasniti radi mogućnosti pouzdanog predviđanja ponašanja i funkcije biomaterijala u željenoj bimedicinskoj primeni. Cilj istraživanja u ovoj doktorskoj disertaciji je bio ispitivanje mogućnosti dobijanja antimikrobnih hidrogelova u različitim oblicima iz koloidnih rastvora alginata sa elektrohemijski sintetisanim nanočesticama srebra i sveobuhvatna karakterizacija proizvedenih nanokompozita u in vitro i in vivo uslovima. In vitro karakterizacija je obuhvatila ispitivanja citotoksičnosti, biomehaničkih karakteristika, antimikrobne aktivnosti i otpuštanja srebra, dok je u in vivo studijama ispitana funkcionalnost nanokompozita za potencijalnu biomedicinsku primenu u tretmanu rana...
PB  - Univerzitet u Beogradu, Tehnološko-metalurški fakultet
T1  - Production and characterization of nanocomposite hydrogels based on alginate and silver nanoparticles for biomedical applications
T1  - Dobijanje i karakterisanje nanokompozitnih hidrogelova na bazi alginata i nanočestica srebra za primenu u biomedicini
UR  - https://hdl.handle.net/21.15107/rcub_technorep_4626
ER  - 

@phdthesis{
author = "Stojkovska, Jasmina",
year = "2015",
abstract = "Development of novel nanocomposite biomaterials for biomedical applications requires comprehensive evaluation and characterization of biomaterials such as determination of the chemical composition, physical properties, biocompatibility and functionality. In addition, successful development of biomaterials for potential biomedical applications requires all inclusive association of all the results for reliable prediction of the behavior and functionality of biomaterials in the desired application. The aim of this doctoral thesis was to investigate possibilities for production of antimicrobial hydrogels in different forms from alginate colloid solutions with electrochemically synthesized silver nanoparticles, as well as comprehensive evaluation of the obtained nanocomposits under in vitro and in vivo conditions. In vitro studies included assessment of cytotoxicity, biomechanical properties, antimicrobial activity and silver release, while in vivo studies comprised functionality evaluation of the nanocomposites for potential biomedical applications in wound tretman..., Razvoj novih nanokompozitnih biomaterijala za biomedicinsku primenu zahteva različita ispitivanja i karakterisanje biomaterijala kako sa stanovišta hemijskog sastava i fizičkih svojstava, tako i sa stanovišta biokompatibilnosti i funkcionalnosti. Uz to, da bi se razvio optimizovan biomaterijal potrebno je rezultate svih ispitivanja povezati i objasniti radi mogućnosti pouzdanog predviđanja ponašanja i funkcije biomaterijala u željenoj bimedicinskoj primeni. Cilj istraživanja u ovoj doktorskoj disertaciji je bio ispitivanje mogućnosti dobijanja antimikrobnih hidrogelova u različitim oblicima iz koloidnih rastvora alginata sa elektrohemijski sintetisanim nanočesticama srebra i sveobuhvatna karakterizacija proizvedenih nanokompozita u in vitro i in vivo uslovima. In vitro karakterizacija je obuhvatila ispitivanja citotoksičnosti, biomehaničkih karakteristika, antimikrobne aktivnosti i otpuštanja srebra, dok je u in vivo studijama ispitana funkcionalnost nanokompozita za potencijalnu biomedicinsku primenu u tretmanu rana...",
publisher = "Univerzitet u Beogradu, Tehnološko-metalurški fakultet",
title = "Production and characterization of nanocomposite hydrogels based on alginate and silver nanoparticles for biomedical applications, Dobijanje i karakterisanje nanokompozitnih hidrogelova na bazi alginata i nanočestica srebra za primenu u biomedicini",
url = "https://hdl.handle.net/21.15107/rcub_technorep_4626"
}

Stojkovska, J.. (2015). Production and characterization of nanocomposite hydrogels based on alginate and silver nanoparticles for biomedical applications. 
Univerzitet u Beogradu, Tehnološko-metalurški fakultet..
https://hdl.handle.net/21.15107/rcub_technorep_4626

Stojkovska J. Production and characterization of nanocomposite hydrogels based on alginate and silver nanoparticles for biomedical applications. 2015;.
https://hdl.handle.net/21.15107/rcub_technorep_4626 .

Stojkovska, Jasmina, "Production and characterization of nanocomposite hydrogels based on alginate and silver nanoparticles for biomedical applications" (2015),
https://hdl.handle.net/21.15107/rcub_technorep_4626 .

TY  - JOUR
AU  - Stojkovska, Jasmina
AU  - Kostić, Danijela
AU  - Jovanović, Zeljka
AU  - Vukašinović-Sekulić, Maja
AU  - Mišković-Stanković, Vesna
AU  - Obradović, Bojana
PY  - 2014
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/2650
AB  - In this work, we present a comprehensive approach to evaluation of alginate microbeads with included silver nanoparticles (AgNPs) at the concentration range of 0.3-5 mM for potential biomedical use by combining cytotoxicity, antibacterial activity, and silver release studies. The microbeads were investigated regarding drying and rehydration showing retention of similar to 80-85% of the initial nanoparticles as determined by UV-vis and SEM analyses. Both wet and dry microbeads were shown to release AgNPs and/or ions inducing similar growth delays of Staphylococcus aureus and Escherichia coli at the total released silver concentrations of similar to 10 mu g/ml. On the other hand, these concentrations were highly toxic for bovine chondrocytes in conventional monolayer cultures while nontoxic when cultured in alginate microbeads under biomimetic conditions in 3D perfusion bioreactors. The applied approach outlined directions for further optimization studies demonstrating Ag/alginate microbeads as potentially attractive components of soft tissue implants as well as antimicrobial wound dressings.
PB  - Elsevier Sci Ltd, Oxford
T2  - Carbohydrate Polymers
T1  - A comprehensive approach to in vitro functional evaluation of Ag/alginate nanocomposite hydrogels
EP  - 314
SP  - 305
VL  - 111
DO  - 10.1016/j.carbpol.2014.04.063
ER  - 

@article{
author = "Stojkovska, Jasmina and Kostić, Danijela and Jovanović, Zeljka and Vukašinović-Sekulić, Maja and Mišković-Stanković, Vesna and Obradović, Bojana",
year = "2014",
abstract = "In this work, we present a comprehensive approach to evaluation of alginate microbeads with included silver nanoparticles (AgNPs) at the concentration range of 0.3-5 mM for potential biomedical use by combining cytotoxicity, antibacterial activity, and silver release studies. The microbeads were investigated regarding drying and rehydration showing retention of similar to 80-85% of the initial nanoparticles as determined by UV-vis and SEM analyses. Both wet and dry microbeads were shown to release AgNPs and/or ions inducing similar growth delays of Staphylococcus aureus and Escherichia coli at the total released silver concentrations of similar to 10 mu g/ml. On the other hand, these concentrations were highly toxic for bovine chondrocytes in conventional monolayer cultures while nontoxic when cultured in alginate microbeads under biomimetic conditions in 3D perfusion bioreactors. The applied approach outlined directions for further optimization studies demonstrating Ag/alginate microbeads as potentially attractive components of soft tissue implants as well as antimicrobial wound dressings.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Carbohydrate Polymers",
title = "A comprehensive approach to in vitro functional evaluation of Ag/alginate nanocomposite hydrogels",
pages = "314-305",
volume = "111",
doi = "10.1016/j.carbpol.2014.04.063"
}

Stojkovska, J., Kostić, D., Jovanović, Z., Vukašinović-Sekulić, M., Mišković-Stanković, V.,& Obradović, B.. (2014). A comprehensive approach to in vitro functional evaluation of Ag/alginate nanocomposite hydrogels. in Carbohydrate Polymers
Elsevier Sci Ltd, Oxford., 111, 305-314.
https://doi.org/10.1016/j.carbpol.2014.04.063

Stojkovska J, Kostić D, Jovanović Z, Vukašinović-Sekulić M, Mišković-Stanković V, Obradović B. A comprehensive approach to in vitro functional evaluation of Ag/alginate nanocomposite hydrogels. in Carbohydrate Polymers. 2014;111:305-314.
doi:10.1016/j.carbpol.2014.04.063 .

Stojkovska, Jasmina, Kostić, Danijela, Jovanović, Zeljka, Vukašinović-Sekulić, Maja, Mišković-Stanković, Vesna, Obradović, Bojana, "A comprehensive approach to in vitro functional evaluation of Ag/alginate nanocomposite hydrogels" in Carbohydrate Polymers, 111 (2014):305-314,
https://doi.org/10.1016/j.carbpol.2014.04.063 . .