TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://dais.sanu.ac.rs/123456789/4600
AB  - Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles
SP  - 776
EP  - 789
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
UR  - https://hdl.handle.net/21.15107/rcub_dais_4600
ER  - 

@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "776-789",
volume = "96",
doi = "10.1016/j.msec.2018.11.073",
url = "https://hdl.handle.net/21.15107/rcub_dais_4600"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C
Elsevier., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073
https://hdl.handle.net/21.15107/rcub_dais_4600

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073
https://hdl.handle.net/21.15107/rcub_dais_4600 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science and Engineering C, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 .,
https://hdl.handle.net/21.15107/rcub_dais_4600 .

TY  - JOUR
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://dais.sanu.ac.rs/123456789/4590
AB  - Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.
PB  - Elsevier
T2  - Materials Science and Engineering C
T1  - Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles
SP  - 776
EP  - 789
VL  - 96
DO  - 10.1016/j.msec.2018.11.073
UR  - https://hdl.handle.net/21.15107/rcub_dais_4590
ER  - 

@article{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "Poly (ε-caprolactone) (PCL) microspheres as a carrier for sustained release of antibacterial agent, selenium nanoparticles (SeNPs), were developed. The obtained PCL/SeNPs microspheres were in the range 1–4 μm with the encapsulation efficiency of about 90%. The degradation process and release behavior of SeNPs from PCL microspheres were investigated in five different degradation media: phosphate buffer solution (PBS), a solution of lipase isolated from the porcine pancreas in PBS, 0.1 M hydrochloric acid (HCl), Pseudomonas aeruginosa PAO1 cell-free extract in PBS and implant fluid (exudate) from the subcutaneously implanted sterile polyvinyl sponges which induce a foreign-body inflammatory reaction. The samples were thoroughly characterized by SEM, TEM, FTIR, XRD, PSA, DSC, confocal microscopy, and ICP-OES techniques. Under physiological conditions at neutral pH, a very slow release of SeNPs occurred (3 and 8% in the case of PBS or PBS + lipase, respectively and after 660 days), while in the acidic environment their presence was not detected. On the other hand, the release in the medium with bacterial extract was much more pronounced, even after 24 h (13%). After 7 days, the concentration of SeNPs reached a maximum of around 30%. Also, 37% of SeNPs have been released after 11 days of incubation of PCL/SeNPs in the implant exudate. These results suggest that the release of SeNPs from PCL was triggered by Pseudomonas aeruginosa PAO1 bacterium as well as by foreign body inflammatory reaction to implant. Furthermore, PCL/SeNPs microspheres were investigated in terms of their biocompatibility. For this purpose, cytotoxicity, the formation of reactive oxygen species (ROS), and genotoxicity were evaluated on HepG2 cell line. The interaction of PCL/SeNPs with phagocytic cell line (Raw 264.7 macrophages) was monitored as well. It was found that the microspheres in investigated concentration range had no acute cytotoxic effects. Finally, SeNPs, as well as PCL/SeNPs, showed a considerable antibacterial activity against Gram-positive bacteria: Staphylococcus aureus (ATCC 25923) and Staphylococcus epidermidis (ATCC 1228). These results suggest that PCL/SeNPs-based system could be an attractive platform for a prolonged prevention of infections accompanying implants. © 2018 Elsevier B.V.",
publisher = "Elsevier",
journal = "Materials Science and Engineering C",
title = "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles",
pages = "776-789",
volume = "96",
doi = "10.1016/j.msec.2018.11.073",
url = "https://hdl.handle.net/21.15107/rcub_dais_4590"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C
Elsevier., 96, 776-789.
https://doi.org/10.1016/j.msec.2018.11.073
https://hdl.handle.net/21.15107/rcub_dais_4590

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. in Materials Science and Engineering C. 2019;96:776-789.
doi:10.1016/j.msec.2018.11.073
https://hdl.handle.net/21.15107/rcub_dais_4590 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles" in Materials Science and Engineering C, 96 (2019):776-789,
https://doi.org/10.1016/j.msec.2018.11.073 .,
https://hdl.handle.net/21.15107/rcub_dais_4590 .

TY  - DATA
AU  - Filipović, Nenad
AU  - Veselinović, Ljiljana
AU  - Ražić, Slavica
AU  - Jeremić, Sanja
AU  - Filipič, Metka
AU  - Žegura, Bojana
AU  - Tomić, Sergej
AU  - Čolić, Miodrag
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://dais.sanu.ac.rs/123456789/5972
AB  - 1. Experimental details for ICP-OES measurements; 1.1. Instrumental and operating conditions; 1.2.Solutions and Reagents; 1.3. Microwave assisted acid digestion; 1.4. Calibration curve 2. Experimental details for biocompatibility investigations of PCL/SeNPs; 2.1. Cell culture; 2.2.Determining citotoxicity of samples - MTT assay; 2.3. Determination of intracellular reactive oxygen species formation – DCFH-DA assay; 2.4. DNA damage (comet assay) Figure 1. SEM image of blank PCL microspheres Figure 2. XRD pattern of commercial PGA used in experiments Figure 3. Interaction with PCL/SeNPs in vivo by infiltrating cells. PCL/SeNPs (4mg/animal) were injected into sterile polyvinyl sponges implanted subcutaneously. The infiltrating cells were collected from the sponges after 3h and stained to anti-CD45/IgG Alexa 488 (Green) and Syto59 nuclear stain. PCL/SeNPs were detected as brightly scattering particles sized about 1-4 μm after 546nm laser excitation either intracellularly within granulocytes (A) or extracellularly (B). Note that some cells expressed strongly CD45 on the membrane and the cytoplasm, whereas others displayed a weak membrane expression and a strong expression in the granular ER at the nucleus level. Table 1. Melting temperatures Tm and corresponding enthalpies (heat) of fusion ΔHf of PCL/SeNPs samples taken after different time from different degradation mediums Table 2. Melting temperatures and corresponding enthalpies of PCL/SeNPs samples taken after different degradation periods from P. aeruginosa CFE medium
T2  - Materials Science and Engineering C
T1  - Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073
UR  - https://hdl.handle.net/21.15107/rcub_dais_5972
ER  - 

@misc{
author = "Filipović, Nenad and Veselinović, Ljiljana and Ražić, Slavica and Jeremić, Sanja and Filipič, Metka and Žegura, Bojana and Tomić, Sergej and Čolić, Miodrag and Stevanović, Magdalena",
year = "2019",
abstract = "1. Experimental details for ICP-OES measurements; 1.1. Instrumental and operating conditions; 1.2.Solutions and Reagents; 1.3. Microwave assisted acid digestion; 1.4. Calibration curve 2. Experimental details for biocompatibility investigations of PCL/SeNPs; 2.1. Cell culture; 2.2.Determining citotoxicity of samples - MTT assay; 2.3. Determination of intracellular reactive oxygen species formation – DCFH-DA assay; 2.4. DNA damage (comet assay) Figure 1. SEM image of blank PCL microspheres Figure 2. XRD pattern of commercial PGA used in experiments Figure 3. Interaction with PCL/SeNPs in vivo by infiltrating cells. PCL/SeNPs (4mg/animal) were injected into sterile polyvinyl sponges implanted subcutaneously. The infiltrating cells were collected from the sponges after 3h and stained to anti-CD45/IgG Alexa 488 (Green) and Syto59 nuclear stain. PCL/SeNPs were detected as brightly scattering particles sized about 1-4 μm after 546nm laser excitation either intracellularly within granulocytes (A) or extracellularly (B). Note that some cells expressed strongly CD45 on the membrane and the cytoplasm, whereas others displayed a weak membrane expression and a strong expression in the granular ER at the nucleus level. Table 1. Melting temperatures Tm and corresponding enthalpies (heat) of fusion ΔHf of PCL/SeNPs samples taken after different time from different degradation mediums Table 2. Melting temperatures and corresponding enthalpies of PCL/SeNPs samples taken after different degradation periods from P. aeruginosa CFE medium",
journal = "Materials Science and Engineering C",
title = "Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073",
url = "https://hdl.handle.net/21.15107/rcub_dais_5972"
}

Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M.,& Stevanović, M.. (2019). Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073. in Materials Science and Engineering C.
https://hdl.handle.net/21.15107/rcub_dais_5972

Filipović N, Veselinović L, Ražić S, Jeremić S, Filipič M, Žegura B, Tomić S, Čolić M, Stevanović M. Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073. in Materials Science and Engineering C. 2019;.
https://hdl.handle.net/21.15107/rcub_dais_5972 .

Filipović, Nenad, Veselinović, Ljiljana, Ražić, Slavica, Jeremić, Sanja, Filipič, Metka, Žegura, Bojana, Tomić, Sergej, Čolić, Miodrag, Stevanović, Magdalena, "Supplementary information for the article: Filipović, N., Veselinović, L., Ražić, S., Jeremić, S., Filipič, M., Žegura, B., Tomić, S., Čolić, M., Stevanović, M., 2019. Poly (ε-caprolactone) microspheres for prolonged release of selenium nanoparticles. Materials Science and Engineering C 96, 776–789. https://doi.org/10.1016/j.msec.2018.11.073" in Materials Science and Engineering C (2019),
https://hdl.handle.net/21.15107/rcub_dais_5972 .

TY  - CONF
AU  - Padovan, Sergio
AU  - Catanzaro, Valeria
AU  - Capuana, Federico
AU  - Grange, Cristina
AU  - Koni, Malvina
AU  - Carrera, Carla
AU  - Filipović, Nenad
AU  - Stevanović, Magdalena
PY  - 2019
UR  - https://eventclass.org/contxt_emim2019/online-program/session?s=PS+22#e83
UR  - https://dais.sanu.ac.rs/123456789/5251
AB  - *Introduction*In regenerative medicine, biocompatible hydrogels are increasingly used to encapsulate therapeutic cells prior to transplantation into the host to enhance their long term survival. Cell embedding within bioengineered hydrogels can shield cells from immune response and provide an optimal life-sustaining microenvironment to therapeutic cells. In addition, cell embedding offers the outstanding opportunity to insert microenvironment-responsive imaging labels within the hydrogel, paving the way for non-invasive monitoring of the extracellular microenvironment within the hydrogel. We have inserted redox-responsive MRI labels within cell-embedding hydrogels to follow-up the microenvironment redox state.*Methods*High molecular weight chitosan polymers were chemically conjugated with a Gd-HPDO3A-chelate through a disulfide bond, and interspersed within alginate-based hydrogel capsules. Human mesenchymal stem cells (hMSCs) as model therapeutic cells were embedded into such imaging labelled hydrogel. Embedded cells were incubated under simulated hypoxiaconditions, while being followed-up by T1-weighted MRI at 7T.*Results*Under reducing conditions, reductive cleavage of the disulfide bond in the Gd-chitosan probe yields a low molecular weight Gd-chelate that eventually diffuses out of the hydrogel capsule. The resulting change of MRI contrast enhancement along time is very sensitive to the oxygenation level within cell capsules. The kinetics of clearance of contrast enhancement is an indirect indicator of the survival of encapsulated cells.*Conclusions*The Gd-chitosan probe we developed is promising to follow-up non-invasively the redox microenvironment within cellembedding hydrogels. This approach will find useful application to monitor whether transplanted cells succeed to restore normal tissue oxygenation levels, especially in regenerative medicine approaches to ischemic diseases.
C3  - European Molecular Imaging Meeting - EMIM 2019, March 19-22, 2019, Scottish Event Campus - SEC, Glasgow, UK: Online Program
T1  - Redox-responsive MRI probes to follow-up hypoxia within cell-embedding hydrogels
UR  - https://hdl.handle.net/21.15107/rcub_dais_5251
ER  - 

@conference{
author = "Padovan, Sergio and Catanzaro, Valeria and Capuana, Federico and Grange, Cristina and Koni, Malvina and Carrera, Carla and Filipović, Nenad and Stevanović, Magdalena",
year = "2019",
abstract = "*Introduction*In regenerative medicine, biocompatible hydrogels are increasingly used to encapsulate therapeutic cells prior to transplantation into the host to enhance their long term survival. Cell embedding within bioengineered hydrogels can shield cells from immune response and provide an optimal life-sustaining microenvironment to therapeutic cells. In addition, cell embedding offers the outstanding opportunity to insert microenvironment-responsive imaging labels within the hydrogel, paving the way for non-invasive monitoring of the extracellular microenvironment within the hydrogel. We have inserted redox-responsive MRI labels within cell-embedding hydrogels to follow-up the microenvironment redox state.*Methods*High molecular weight chitosan polymers were chemically conjugated with a Gd-HPDO3A-chelate through a disulfide bond, and interspersed within alginate-based hydrogel capsules. Human mesenchymal stem cells (hMSCs) as model therapeutic cells were embedded into such imaging labelled hydrogel. Embedded cells were incubated under simulated hypoxiaconditions, while being followed-up by T1-weighted MRI at 7T.*Results*Under reducing conditions, reductive cleavage of the disulfide bond in the Gd-chitosan probe yields a low molecular weight Gd-chelate that eventually diffuses out of the hydrogel capsule. The resulting change of MRI contrast enhancement along time is very sensitive to the oxygenation level within cell capsules. The kinetics of clearance of contrast enhancement is an indirect indicator of the survival of encapsulated cells.*Conclusions*The Gd-chitosan probe we developed is promising to follow-up non-invasively the redox microenvironment within cellembedding hydrogels. This approach will find useful application to monitor whether transplanted cells succeed to restore normal tissue oxygenation levels, especially in regenerative medicine approaches to ischemic diseases.",
journal = "European Molecular Imaging Meeting - EMIM 2019, March 19-22, 2019, Scottish Event Campus - SEC, Glasgow, UK: Online Program",
title = "Redox-responsive MRI probes to follow-up hypoxia within cell-embedding hydrogels",
url = "https://hdl.handle.net/21.15107/rcub_dais_5251"
}

Padovan, S., Catanzaro, V., Capuana, F., Grange, C., Koni, M., Carrera, C., Filipović, N.,& Stevanović, M.. (2019). Redox-responsive MRI probes to follow-up hypoxia within cell-embedding hydrogels. in European Molecular Imaging Meeting - EMIM 2019, March 19-22, 2019, Scottish Event Campus - SEC, Glasgow, UK: Online Program.
https://hdl.handle.net/21.15107/rcub_dais_5251

Padovan S, Catanzaro V, Capuana F, Grange C, Koni M, Carrera C, Filipović N, Stevanović M. Redox-responsive MRI probes to follow-up hypoxia within cell-embedding hydrogels. in European Molecular Imaging Meeting - EMIM 2019, March 19-22, 2019, Scottish Event Campus - SEC, Glasgow, UK: Online Program. 2019;.
https://hdl.handle.net/21.15107/rcub_dais_5251 .

Padovan, Sergio, Catanzaro, Valeria, Capuana, Federico, Grange, Cristina, Koni, Malvina, Carrera, Carla, Filipović, Nenad, Stevanović, Magdalena, "Redox-responsive MRI probes to follow-up hypoxia within cell-embedding hydrogels" in European Molecular Imaging Meeting - EMIM 2019, March 19-22, 2019, Scottish Event Campus - SEC, Glasgow, UK: Online Program (2019),
https://hdl.handle.net/21.15107/rcub_dais_5251 .

TY  - CONF
AU  - Filipović, Nenad
AU  - Digilio, Giuseppe
AU  - Catanzaro, Valeria
AU  - Capuana, Federico
AU  - Cutrin, Juan C.
AU  - Carniato, Fabio
AU  - Porta, Stefano
AU  - Grange, Cristina
AU  - Stevanović, Magdalena
PY  - 2018
UR  - https://dais.sanu.ac.rs/123456789/4721
AB  - Cell therapy is promising strategy that has attracted a lot of attention recently regarding regeneration of diverse tissues and treatment of various pathological conditions. Despite its great potential, several issues still need to be addressed. Among them administration route and dose, microenvironment conditions and host immune response are recognized as a major causes which lead to cells transplantation failure. In this work it is presented novel microstructural system based on biodegradable polymer poly(lactide-co-glycolide) (PLGA) and combination of biocompatible polyvinyl alcohol (PVA) and chitosan, as a scaffold for human mesenchymal stem cells (hMSCs) growth. The obtained microparticles with diameter 200-600 μm showed full biocompatibility with human hMSCs. Besides serving as a solid support, polymeric particles provided controlled release of contrast agent - gadolinium fluoride nanoparticles (Gd-NP) up to 5 weeks. The release of Gd-NP is enhanced by acidic conditions. Magnetic Resonance Imaging (MRI) of the samples embedded in 1% agar showed that contrast enhancement in T1-weighted (T1w) MR images is influenced by the amount of released Gd-NP. Based on these preliminary results, presented theranostic system could be considered for cells grafting.
PB  - Belgrade : Institute of Technical Sciences of SASA
C3  - Program and the Book of Abstracts / Seventeenth Young Researchers' Conference Materials Sciences and Engineering, December 5-7, 2018, Belgrade, Serbia
T1  - Biodegradable microparticles as scaffolds for cell therapy
SP  - 7
EP  - 7
UR  - https://hdl.handle.net/21.15107/rcub_dais_4721
ER  - 

@conference{
author = "Filipović, Nenad and Digilio, Giuseppe and Catanzaro, Valeria and Capuana, Federico and Cutrin, Juan C. and Carniato, Fabio and Porta, Stefano and Grange, Cristina and Stevanović, Magdalena",
year = "2018",
abstract = "Cell therapy is promising strategy that has attracted a lot of attention recently regarding regeneration of diverse tissues and treatment of various pathological conditions. Despite its great potential, several issues still need to be addressed. Among them administration route and dose, microenvironment conditions and host immune response are recognized as a major causes which lead to cells transplantation failure. In this work it is presented novel microstructural system based on biodegradable polymer poly(lactide-co-glycolide) (PLGA) and combination of biocompatible polyvinyl alcohol (PVA) and chitosan, as a scaffold for human mesenchymal stem cells (hMSCs) growth. The obtained microparticles with diameter 200-600 μm showed full biocompatibility with human hMSCs. Besides serving as a solid support, polymeric particles provided controlled release of contrast agent - gadolinium fluoride nanoparticles (Gd-NP) up to 5 weeks. The release of Gd-NP is enhanced by acidic conditions. Magnetic Resonance Imaging (MRI) of the samples embedded in 1% agar showed that contrast enhancement in T1-weighted (T1w) MR images is influenced by the amount of released Gd-NP. Based on these preliminary results, presented theranostic system could be considered for cells grafting.",
publisher = "Belgrade : Institute of Technical Sciences of SASA",
journal = "Program and the Book of Abstracts / Seventeenth Young Researchers' Conference Materials Sciences and Engineering, December 5-7, 2018, Belgrade, Serbia",
title = "Biodegradable microparticles as scaffolds for cell therapy",
pages = "7-7",
url = "https://hdl.handle.net/21.15107/rcub_dais_4721"
}

Filipović, N., Digilio, G., Catanzaro, V., Capuana, F., Cutrin, J. C., Carniato, F., Porta, S., Grange, C.,& Stevanović, M.. (2018). Biodegradable microparticles as scaffolds for cell therapy. in Program and the Book of Abstracts / Seventeenth Young Researchers' Conference Materials Sciences and Engineering, December 5-7, 2018, Belgrade, Serbia
Belgrade : Institute of Technical Sciences of SASA., 7-7.
https://hdl.handle.net/21.15107/rcub_dais_4721

Filipović N, Digilio G, Catanzaro V, Capuana F, Cutrin JC, Carniato F, Porta S, Grange C, Stevanović M. Biodegradable microparticles as scaffolds for cell therapy. in Program and the Book of Abstracts / Seventeenth Young Researchers' Conference Materials Sciences and Engineering, December 5-7, 2018, Belgrade, Serbia. 2018;:7-7.
https://hdl.handle.net/21.15107/rcub_dais_4721 .

Filipović, Nenad, Digilio, Giuseppe, Catanzaro, Valeria, Capuana, Federico, Cutrin, Juan C., Carniato, Fabio, Porta, Stefano, Grange, Cristina, Stevanović, Magdalena, "Biodegradable microparticles as scaffolds for cell therapy" in Program and the Book of Abstracts / Seventeenth Young Researchers' Conference Materials Sciences and Engineering, December 5-7, 2018, Belgrade, Serbia (2018):7-7,
https://hdl.handle.net/21.15107/rcub_dais_4721 .

TY  - CONF
AU  - Capuana, Federico
AU  - Padovan, Sergio
AU  - Grange, Cristina
AU  - Catanzaro, Valeria
AU  - Cutrin, J. C.
AU  - Stevanović, Magdalena
AU  - Filipović, Nenad
AU  - Digilio, G.
PY  - 2018
UR  - http://eventclass.org/contxt_emim2018/online-program/session?s=101#153
UR  - https://dais.sanu.ac.rs/123456789/4667
AB  - Introduction: Cell encapsulation by hydrogels is intended to shield transplanted cells from the host hostile environment by preventing the infiltration of host immune cells. Cell scaffolding by solid biocompatible microparticles is intended to provide a structural support to implanted cells and to mimic the extracellular matrix, allowing cells to proliferate and/or differentiate in the desired way. We present strategies to label scaffolding biomaterials with microenvironment responsive MRI probes, for applications in the follow-up of cell transplants.

Methods: Microparticles (MPs) based on PLGA/chitosan were incorporated with gadolinium fluoride nanoparticles (GdNPs), as the MRI T1-contrast agent. The system is designed such to release Gd-NPs in the extracellular matrix (ECM), thus activating MRI contrast, unless MPs are attacked by the immune system (Foreign Body Response, FBR). To proof the concept, PLGA-based MPs were seeded with hMSCs and implanted into either immunocompetent or immunocompromised mice, and the transplants were followed-up by MRI for three weeks. Ex-vivo histologic assessment was carried out at the end of the follow-up.

Results/Discussion: Immunocompetent mice showed poor activation, if any, of MRI contrast within the cell graft. Immunocompromised mice, on the other hand, showed a progressive activation of MRI contrast. Ex-vivo histology showed extensive FBR directed against microparticles in immunocompetent mice, with some surviving hMSCs in the ECM but not on the scaffold surface. No significant FBR was detected in immunocompromised mice, and hMSCs were still adhering to the scaffolds.

Conclusions: The proposed system is able to assess whether or not cell grafts are subjected to innate immune response, an event that is likely correlated to the loss of transplanted cells.
PB  - European Society for Molecular Imaging
C3  - European Molecular Imaging Meeting - EMIM 2018, March 20-23, Kursaal San Sebastian, Spain : Online Program
T1  - Biocompatible Materials labelled with Microenvironment Responsive MRI Probes for the follow-up of Cell Transplants
UR  - https://hdl.handle.net/21.15107/rcub_dais_4667
ER  - 

@conference{
author = "Capuana, Federico and Padovan, Sergio and Grange, Cristina and Catanzaro, Valeria and Cutrin, J. C. and Stevanović, Magdalena and Filipović, Nenad and Digilio, G.",
year = "2018",
abstract = "Introduction: Cell encapsulation by hydrogels is intended to shield transplanted cells from the host hostile environment by preventing the infiltration of host immune cells. Cell scaffolding by solid biocompatible microparticles is intended to provide a structural support to implanted cells and to mimic the extracellular matrix, allowing cells to proliferate and/or differentiate in the desired way. We present strategies to label scaffolding biomaterials with microenvironment responsive MRI probes, for applications in the follow-up of cell transplants.

Methods: Microparticles (MPs) based on PLGA/chitosan were incorporated with gadolinium fluoride nanoparticles (GdNPs), as the MRI T1-contrast agent. The system is designed such to release Gd-NPs in the extracellular matrix (ECM), thus activating MRI contrast, unless MPs are attacked by the immune system (Foreign Body Response, FBR). To proof the concept, PLGA-based MPs were seeded with hMSCs and implanted into either immunocompetent or immunocompromised mice, and the transplants were followed-up by MRI for three weeks. Ex-vivo histologic assessment was carried out at the end of the follow-up.

Results/Discussion: Immunocompetent mice showed poor activation, if any, of MRI contrast within the cell graft. Immunocompromised mice, on the other hand, showed a progressive activation of MRI contrast. Ex-vivo histology showed extensive FBR directed against microparticles in immunocompetent mice, with some surviving hMSCs in the ECM but not on the scaffold surface. No significant FBR was detected in immunocompromised mice, and hMSCs were still adhering to the scaffolds.

Conclusions: The proposed system is able to assess whether or not cell grafts are subjected to innate immune response, an event that is likely correlated to the loss of transplanted cells.",
publisher = "European Society for Molecular Imaging",
journal = "European Molecular Imaging Meeting - EMIM 2018, March 20-23, Kursaal San Sebastian, Spain : Online Program",
title = "Biocompatible Materials labelled with Microenvironment Responsive MRI Probes for the follow-up of Cell Transplants",
url = "https://hdl.handle.net/21.15107/rcub_dais_4667"
}

Capuana, F., Padovan, S., Grange, C., Catanzaro, V., Cutrin, J. C., Stevanović, M., Filipović, N.,& Digilio, G.. (2018). Biocompatible Materials labelled with Microenvironment Responsive MRI Probes for the follow-up of Cell Transplants. in European Molecular Imaging Meeting - EMIM 2018, March 20-23, Kursaal San Sebastian, Spain : Online Program
European Society for Molecular Imaging..
https://hdl.handle.net/21.15107/rcub_dais_4667

Capuana F, Padovan S, Grange C, Catanzaro V, Cutrin JC, Stevanović M, Filipović N, Digilio G. Biocompatible Materials labelled with Microenvironment Responsive MRI Probes for the follow-up of Cell Transplants. in European Molecular Imaging Meeting - EMIM 2018, March 20-23, Kursaal San Sebastian, Spain : Online Program. 2018;.
https://hdl.handle.net/21.15107/rcub_dais_4667 .

Capuana, Federico, Padovan, Sergio, Grange, Cristina, Catanzaro, Valeria, Cutrin, J. C., Stevanović, Magdalena, Filipović, Nenad, Digilio, G., "Biocompatible Materials labelled with Microenvironment Responsive MRI Probes for the follow-up of Cell Transplants" in European Molecular Imaging Meeting - EMIM 2018, March 20-23, Kursaal San Sebastian, Spain : Online Program (2018),
https://hdl.handle.net/21.15107/rcub_dais_4667 .