Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200143 (University of Belgrade, Faculty of Veterinary Medicine)

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Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 451-03-68/2020-14/200143 (University of Belgrade, Faculty of Veterinary Medicine) (en)
Ministarstvo prosvete, nauke i tehnološkog razvoja Republike Srbije, Ugovor br. 451-03-68/2020-14/200143 (Univerzitet u Beogradu, Fakultet veterinarske medicine) (sr_RS)
Министарство просвете, науке и технолошког развоја Републике Србије, Уговор бр. 451-03-68/2020-14/200143 (Универзитет у Београду, Факултет ветеринарске медицине) (sr)
Authors

Publications

Animal models in biocompatibility assessments of implants in soft and hard tissues

Prokić, Bogomir Bolka; Lužajić Božinovski, Tijana; Gajdov, Vladimir; Milošević, Ivan; Todorović, Vera; Đošić, Marija; Mišković-Stanković, Vesna; Marković, Danica

(University of Belgrade, Faculty of Veterinary Medicine, 2022)

TY  - JOUR
AU  - Prokić, Bogomir Bolka
AU  - Lužajić Božinovski, Tijana
AU  - Gajdov, Vladimir
AU  - Milošević, Ivan
AU  - Todorović, Vera
AU  - Đošić, Marija
AU  - Mišković-Stanković, Vesna
AU  - Marković, Danica
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5302
AB  - The ethical dilemmas of using animals as in vivo models in preclinical and clinical examinations have been increasingly present in recent decades. Small laboratory animals (rats, rabbits) will continue to be used because they are cost-effective and permit the formation of statistically testable cohort groups; a task that, for financial, maintenance and care reasons, is almost prohibitive for larger animals. Technological advances in the production of new biomaterials for clinical use are enormous, but screening tests and methods used to assess biocompatibility lag behind these advances. The assessment of biological responses is slow and based on millennial recovery mechanisms in eukaryotic organisms. Therefore, the goal of researchers in this field is to re-evaluate old methods of biocompatibility assessment and introduce new methods of evaluation, especially for in vivo testing. In that sense, a revision of the ISO standards was planned and conducted in 2017, which insisted on cytotoxicity testing in cell lines and produced concrete proposals on how biocompatibility should be quantified. In vivo biocompatibility evaluation of biomaterials used for soft tissue recovery commonly utilises rats. Rabbits are recommended for implants used for hard tissues, because of the rabbit’s size, the possibility of implanting the biomaterials on a larger bone surface, and because of the peculiarities of rabbit bone tissue that favours rapid recovery after bone defects and enables easy reading of the results.
AB  - Etičke dileme koje proizilaze iz korišćenja životinja kao in vivo modela u pretkliničkim
i kliničkim ispitivanjima su sve prisutnije poslednjih decenija. Male laboratorijske
životinje će se koristiti i u neposrednoj budućnosti zbog ekonomske isplatljivosti, kao i
zbog toga što omogućavaju formiranje grupa iz kojih se mogu dobiti statistički obradivi
podaci, što nije slučaj sa velikim životinjama. Tehnološki napredak u proizvodnji novih
biomaterijala za kliničku primenu je ogroman, ali skrining testovi i metode koje se
koriste za procenu biokompatibilnosti zaostaju za tim napretkom. Procena biološkog
odgovora nakon implantacije biomaterijala je spora i zasniva se na milenijumskim
mehanizmima oporavka prisutnim kod eukariota. Cilj istraživača iz ove oblasti je
preispitivanje klasičnih metoda procene biokompatibilnosti i uvođenje novih, posebno
za in vivo istraživanja. U cilju ostvarivanja ovog zadatka, u 2017. godini je sprovedena
revizija odgovarajućih ISO standarda, pa se sada insistira na ispitivanju citotoksičnosti
novih biomaterijala na ćelijskim linijama. Takođe, neki istraživači su izneli konkretne
predloge o uspostvaljnju novih načina procenjivanja biokompatibilnosti. U proceni
biokompatibilnosti biomaterijala in vivo koji se koriste za oporavak mekog tkiva,
uobičajeno se koriste pacovi, dok se kunići preporučuju za implantate koji se koriste
za tvrda tkiva zbog njihove veličine i mogućnosti implantacije biomaterijala na veću
površinu kostiju, kao i zbog osobenosti koštanog tkiva kunića koje se brže oporavlja
nakon oštećenja i omogućava lako očitavanje rezultata.
PB  - University of Belgrade, Faculty of Veterinary Medicine
T2  - Veterinarski Glasnik
T1  - Animal models in biocompatibility assessments of implants in soft and hard tissues
T1  - PRIMENA ANIMALNIH MODELA U PROCENI BIOKOMPATIBILNOSTI IMPLANTATA ZA TVRDA I MEKA TKIVA
IS  - 1
VL  - 76
DO  - 10.2298/VETGL210322005P
ER  - 
@article{
author = "Prokić, Bogomir Bolka and Lužajić Božinovski, Tijana and Gajdov, Vladimir and Milošević, Ivan and Todorović, Vera and Đošić, Marija and Mišković-Stanković, Vesna and Marković, Danica",
year = "2022",
abstract = "The ethical dilemmas of using animals as in vivo models in preclinical and clinical examinations have been increasingly present in recent decades. Small laboratory animals (rats, rabbits) will continue to be used because they are cost-effective and permit the formation of statistically testable cohort groups; a task that, for financial, maintenance and care reasons, is almost prohibitive for larger animals. Technological advances in the production of new biomaterials for clinical use are enormous, but screening tests and methods used to assess biocompatibility lag behind these advances. The assessment of biological responses is slow and based on millennial recovery mechanisms in eukaryotic organisms. Therefore, the goal of researchers in this field is to re-evaluate old methods of biocompatibility assessment and introduce new methods of evaluation, especially for in vivo testing. In that sense, a revision of the ISO standards was planned and conducted in 2017, which insisted on cytotoxicity testing in cell lines and produced concrete proposals on how biocompatibility should be quantified. In vivo biocompatibility evaluation of biomaterials used for soft tissue recovery commonly utilises rats. Rabbits are recommended for implants used for hard tissues, because of the rabbit’s size, the possibility of implanting the biomaterials on a larger bone surface, and because of the peculiarities of rabbit bone tissue that favours rapid recovery after bone defects and enables easy reading of the results., Etičke dileme koje proizilaze iz korišćenja životinja kao in vivo modela u pretkliničkim
i kliničkim ispitivanjima su sve prisutnije poslednjih decenija. Male laboratorijske
životinje će se koristiti i u neposrednoj budućnosti zbog ekonomske isplatljivosti, kao i
zbog toga što omogućavaju formiranje grupa iz kojih se mogu dobiti statistički obradivi
podaci, što nije slučaj sa velikim životinjama. Tehnološki napredak u proizvodnji novih
biomaterijala za kliničku primenu je ogroman, ali skrining testovi i metode koje se
koriste za procenu biokompatibilnosti zaostaju za tim napretkom. Procena biološkog
odgovora nakon implantacije biomaterijala je spora i zasniva se na milenijumskim
mehanizmima oporavka prisutnim kod eukariota. Cilj istraživača iz ove oblasti je
preispitivanje klasičnih metoda procene biokompatibilnosti i uvođenje novih, posebno
za in vivo istraživanja. U cilju ostvarivanja ovog zadatka, u 2017. godini je sprovedena
revizija odgovarajućih ISO standarda, pa se sada insistira na ispitivanju citotoksičnosti
novih biomaterijala na ćelijskim linijama. Takođe, neki istraživači su izneli konkretne
predloge o uspostvaljnju novih načina procenjivanja biokompatibilnosti. U proceni
biokompatibilnosti biomaterijala in vivo koji se koriste za oporavak mekog tkiva,
uobičajeno se koriste pacovi, dok se kunići preporučuju za implantate koji se koriste
za tvrda tkiva zbog njihove veličine i mogućnosti implantacije biomaterijala na veću
površinu kostiju, kao i zbog osobenosti koštanog tkiva kunića koje se brže oporavlja
nakon oštećenja i omogućava lako očitavanje rezultata.",
publisher = "University of Belgrade, Faculty of Veterinary Medicine",
journal = "Veterinarski Glasnik",
title = "Animal models in biocompatibility assessments of implants in soft and hard tissues, PRIMENA ANIMALNIH MODELA U PROCENI BIOKOMPATIBILNOSTI IMPLANTATA ZA TVRDA I MEKA TKIVA",
number = "1",
volume = "76",
doi = "10.2298/VETGL210322005P"
}
Prokić, B. B., Lužajić Božinovski, T., Gajdov, V., Milošević, I., Todorović, V., Đošić, M., Mišković-Stanković, V.,& Marković, D.. (2022). Animal models in biocompatibility assessments of implants in soft and hard tissues. in Veterinarski Glasnik
University of Belgrade, Faculty of Veterinary Medicine., 76(1).
https://doi.org/10.2298/VETGL210322005P
Prokić BB, Lužajić Božinovski T, Gajdov V, Milošević I, Todorović V, Đošić M, Mišković-Stanković V, Marković D. Animal models in biocompatibility assessments of implants in soft and hard tissues. in Veterinarski Glasnik. 2022;76(1).
doi:10.2298/VETGL210322005P .
Prokić, Bogomir Bolka, Lužajić Božinovski, Tijana, Gajdov, Vladimir, Milošević, Ivan, Todorović, Vera, Đošić, Marija, Mišković-Stanković, Vesna, Marković, Danica, "Animal models in biocompatibility assessments of implants in soft and hard tissues" in Veterinarski Glasnik, 76, no. 1 (2022),
https://doi.org/10.2298/VETGL210322005P . .
2
2

Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats

Lužajić-Božinovski, Tijana; Todorovic, Vera; Milosevic, Ivan; Prokić, Bogomir Bolka; Gajdov, Vladimir; Nešović, Katarina; Mišković-Stanković, Vesna; Markovic, Danica

(2022)

TY  - JOUR
AU  - Lužajić-Božinovski, Tijana
AU  - Todorovic, Vera
AU  - Milosevic, Ivan
AU  - Prokić, Bogomir Bolka
AU  - Gajdov, Vladimir
AU  - Nešović, Katarina
AU  - Mišković-Stanković, Vesna
AU  - Markovic, Danica
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5021
AB  - Biocompatibility of materials is one of the most important conditions for their successful application in tissue regeneration and repair. Cell-surface interactions stimulate adhesion and activation of macrophages whose acquaintance can assist in designing novel biomaterials that promote favorable macrophage-biomaterial surface interactions for clinical application. This study is designed to determine the distribution and number of macrophages as a means of biocompatibility evaluation of two newly synthesized materials [silver/poly(vinyl alcohol) (Ag/PVA) and silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) nanocomposite hydrogels] in vivo, with approval of the Ethics Committee of the Faculty of Veterinary Medicine, University of Belgrade. Macrophages and giant cells were analyzed in tissue sections stained by routine H&E and immunohistochemical methods (CD68(+)). Statistical relevance was determined in the statistical software package SPSS 20 (IBM corp). The results of the study in terms of the number of giant cells localized around the implant showed that their number was highest on the seventh postoperative day (p.o.d.) in the group implanted with Ag/PVA hydrogels, and on the 30th p.o.d. in the group implanted with Ag/PVA/Gr. Interestingly, the number of macrophages measured in the capsular and pericapsular space was highest in the group implanted with the commercial Suprasorb
T2  - Journal of Biomaterials Applications
T1  - Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats
EP  - 1125
IS  - 6
SP  - 1111
VL  - 36
DO  - 10.1177/08853282211046119
ER  - 
@article{
author = "Lužajić-Božinovski, Tijana and Todorovic, Vera and Milosevic, Ivan and Prokić, Bogomir Bolka and Gajdov, Vladimir and Nešović, Katarina and Mišković-Stanković, Vesna and Markovic, Danica",
year = "2022",
abstract = "Biocompatibility of materials is one of the most important conditions for their successful application in tissue regeneration and repair. Cell-surface interactions stimulate adhesion and activation of macrophages whose acquaintance can assist in designing novel biomaterials that promote favorable macrophage-biomaterial surface interactions for clinical application. This study is designed to determine the distribution and number of macrophages as a means of biocompatibility evaluation of two newly synthesized materials [silver/poly(vinyl alcohol) (Ag/PVA) and silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) nanocomposite hydrogels] in vivo, with approval of the Ethics Committee of the Faculty of Veterinary Medicine, University of Belgrade. Macrophages and giant cells were analyzed in tissue sections stained by routine H&E and immunohistochemical methods (CD68(+)). Statistical relevance was determined in the statistical software package SPSS 20 (IBM corp). The results of the study in terms of the number of giant cells localized around the implant showed that their number was highest on the seventh postoperative day (p.o.d.) in the group implanted with Ag/PVA hydrogels, and on the 30th p.o.d. in the group implanted with Ag/PVA/Gr. Interestingly, the number of macrophages measured in the capsular and pericapsular space was highest in the group implanted with the commercial Suprasorb",
journal = "Journal of Biomaterials Applications",
title = "Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats",
pages = "1125-1111",
number = "6",
volume = "36",
doi = "10.1177/08853282211046119"
}
Lužajić-Božinovski, T., Todorovic, V., Milosevic, I., Prokić, B. B., Gajdov, V., Nešović, K., Mišković-Stanković, V.,& Markovic, D.. (2022). Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats. in Journal of Biomaterials Applications, 36(6), 1111-1125.
https://doi.org/10.1177/08853282211046119
Lužajić-Božinovski T, Todorovic V, Milosevic I, Prokić BB, Gajdov V, Nešović K, Mišković-Stanković V, Markovic D. Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats. in Journal of Biomaterials Applications. 2022;36(6):1111-1125.
doi:10.1177/08853282211046119 .
Lužajić-Božinovski, Tijana, Todorovic, Vera, Milosevic, Ivan, Prokić, Bogomir Bolka, Gajdov, Vladimir, Nešović, Katarina, Mišković-Stanković, Vesna, Markovic, Danica, "Macrophages, the main marker in biocompatibility evaluation of new hydrogels after subcutaneous implantation in rats" in Journal of Biomaterials Applications, 36, no. 6 (2022):1111-1125,
https://doi.org/10.1177/08853282211046119 . .
11
1
1

Evaluation of soft tissue regenerative processes after subcutaneous implantation of silver/ poly(vinyl alcohol) and novel silver/poly(vinyl alcohol)/graphene hydrogels in an animal model

Lužajić-Božinovski, Tijana; Todorovic, Vera; Milosevic, Ivan; Gajdov, Vladimir; Prokić, Bogomir Bolka; Nešović, Katarina; Mišković-Stanković, Vesna; Markovic, Danica

(2021)

TY  - JOUR
AU  - Lužajić-Božinovski, Tijana
AU  - Todorovic, Vera
AU  - Milosevic, Ivan
AU  - Gajdov, Vladimir
AU  - Prokić, Bogomir Bolka
AU  - Nešović, Katarina
AU  - Mišković-Stanković, Vesna
AU  - Markovic, Danica
PY  - 2021
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/4812
AB  - A newly produced biomaterial is necessarily subject of standards, which are performed in vivo on animal models. For the evaluation of soft tissue regenerative possibilities after subcutaneous implantation of biomaterials - silver/poly(vinyl alcohol) (Ag/PVA) and novel silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) provided for clinical use, sixteen rats were used, according to the instructions of international standards, ISO 10993-6, 2007. Histological sections were observed 7, 15, 30 and 60 days after grafting. These hydrogels were produced by in situ electrochemical synthesis of silver nanoparticles in the polymer matrices, which enabled obtaining completely safe and biocompatible materials, free from any additional toxic chemical reducing agents. Surgical implantation of hydrogels was done according to the permission of the Ethical Committee of the Faculty of Veterinary Medicine, University of Belgrade. Immunohistochemical (IHC) studies included the assessment of smooth muscle expression actin in blood vessels (alpha-SMA), the expression of laminin and type I and type III collagen in the skin structures, and, the determination of cell proliferation marker expression (Ki-67) keratinocytes. The results were assessed in a semiquantitative manner. The data were analyzed in the statistical software package IBM SPSS 20. The conclusions indicated that Ag/PVA/Gr might be used as wound dressings to enhance the tissue healing potential and established faster integration and shorter retention in the tissue.
T2  - Acta Veterinaria-Beograd
T1  - Evaluation of soft tissue regenerative processes after subcutaneous implantation of silver/ poly(vinyl alcohol) and novel silver/poly(vinyl alcohol)/graphene hydrogels in an animal model
EP  - 302
IS  - 3
SP  - 285
VL  - 71
DO  - 10.2478/acve-2021-0025
ER  - 
@article{
author = "Lužajić-Božinovski, Tijana and Todorovic, Vera and Milosevic, Ivan and Gajdov, Vladimir and Prokić, Bogomir Bolka and Nešović, Katarina and Mišković-Stanković, Vesna and Markovic, Danica",
year = "2021",
abstract = "A newly produced biomaterial is necessarily subject of standards, which are performed in vivo on animal models. For the evaluation of soft tissue regenerative possibilities after subcutaneous implantation of biomaterials - silver/poly(vinyl alcohol) (Ag/PVA) and novel silver/poly(vinyl alcohol)/graphene (Ag/PVA/Gr) provided for clinical use, sixteen rats were used, according to the instructions of international standards, ISO 10993-6, 2007. Histological sections were observed 7, 15, 30 and 60 days after grafting. These hydrogels were produced by in situ electrochemical synthesis of silver nanoparticles in the polymer matrices, which enabled obtaining completely safe and biocompatible materials, free from any additional toxic chemical reducing agents. Surgical implantation of hydrogels was done according to the permission of the Ethical Committee of the Faculty of Veterinary Medicine, University of Belgrade. Immunohistochemical (IHC) studies included the assessment of smooth muscle expression actin in blood vessels (alpha-SMA), the expression of laminin and type I and type III collagen in the skin structures, and, the determination of cell proliferation marker expression (Ki-67) keratinocytes. The results were assessed in a semiquantitative manner. The data were analyzed in the statistical software package IBM SPSS 20. The conclusions indicated that Ag/PVA/Gr might be used as wound dressings to enhance the tissue healing potential and established faster integration and shorter retention in the tissue.",
journal = "Acta Veterinaria-Beograd",
title = "Evaluation of soft tissue regenerative processes after subcutaneous implantation of silver/ poly(vinyl alcohol) and novel silver/poly(vinyl alcohol)/graphene hydrogels in an animal model",
pages = "302-285",
number = "3",
volume = "71",
doi = "10.2478/acve-2021-0025"
}
Lužajić-Božinovski, T., Todorovic, V., Milosevic, I., Gajdov, V., Prokić, B. B., Nešović, K., Mišković-Stanković, V.,& Markovic, D.. (2021). Evaluation of soft tissue regenerative processes after subcutaneous implantation of silver/ poly(vinyl alcohol) and novel silver/poly(vinyl alcohol)/graphene hydrogels in an animal model. in Acta Veterinaria-Beograd, 71(3), 285-302.
https://doi.org/10.2478/acve-2021-0025
Lužajić-Božinovski T, Todorovic V, Milosevic I, Gajdov V, Prokić BB, Nešović K, Mišković-Stanković V, Markovic D. Evaluation of soft tissue regenerative processes after subcutaneous implantation of silver/ poly(vinyl alcohol) and novel silver/poly(vinyl alcohol)/graphene hydrogels in an animal model. in Acta Veterinaria-Beograd. 2021;71(3):285-302.
doi:10.2478/acve-2021-0025 .
Lužajić-Božinovski, Tijana, Todorovic, Vera, Milosevic, Ivan, Gajdov, Vladimir, Prokić, Bogomir Bolka, Nešović, Katarina, Mišković-Stanković, Vesna, Markovic, Danica, "Evaluation of soft tissue regenerative processes after subcutaneous implantation of silver/ poly(vinyl alcohol) and novel silver/poly(vinyl alcohol)/graphene hydrogels in an animal model" in Acta Veterinaria-Beograd, 71, no. 3 (2021):285-302,
https://doi.org/10.2478/acve-2021-0025 . .
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3