TY  - JOUR
AU  - Pejić, Biljana
AU  - Medović-Baralić, Adela
AU  - Kojić, Zvezdana
AU  - Škundrić, Petar
AU  - Kostić, Mirjana
PY  - 2015
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/2983
AB  - Oxidized cellulose has a long history of safe and effective use in medical applications. In this paper, research has been directed towards obtaining hormone-active cellulose fibers in the form of an artificial insulin depot, and examination of its biocompatibility regarding cytotoxicity, sensitization, and irritation. The procedure of obtaining the fibrous insulin depot is based on the modification of cotton fibers with sodium periodate, followed by chemisorption of insulin from insulin aqueous solutions. In order to optimize the insulin chemisorption process, the influence of the fiber structure parameters, i.e. the aldehyde group content and iodine sorption value (ISV) on the chemisorption capacity was examined. The obtained artificial depot, containing approximate to 55 mg insulin/g of fibers, has been characterized in vitro by investigation of the desorption kinetics of the insulin from the fibrous depot. It has been shown that insulin is controllably released in quantities of 1.3-1.6 mg of insulin during 24 hours, in the course of 20 days. The results of biocompatibility tests have shown that the examined artificial depot neither shows irritating effects nor provokes sensitizing or cytotoxic effects. Therefore, these materials are acceptable for use in a direct contact with tissue of a living organism.
PB  - Korean Fiber Soc, Seoul
T2  - Fibers and Polymers
T1  - Oxidized Cotton as a Substrate for the Preparation of Hormone-Active Fibers-Characterization, Efficiency and Biocompatibility
EP  - 1004
IS  - 5
SP  - 997
VL  - 16
DO  - 10.1007/s12221-015-0997-6
ER  - 

@article{
author = "Pejić, Biljana and Medović-Baralić, Adela and Kojić, Zvezdana and Škundrić, Petar and Kostić, Mirjana",
year = "2015",
abstract = "Oxidized cellulose has a long history of safe and effective use in medical applications. In this paper, research has been directed towards obtaining hormone-active cellulose fibers in the form of an artificial insulin depot, and examination of its biocompatibility regarding cytotoxicity, sensitization, and irritation. The procedure of obtaining the fibrous insulin depot is based on the modification of cotton fibers with sodium periodate, followed by chemisorption of insulin from insulin aqueous solutions. In order to optimize the insulin chemisorption process, the influence of the fiber structure parameters, i.e. the aldehyde group content and iodine sorption value (ISV) on the chemisorption capacity was examined. The obtained artificial depot, containing approximate to 55 mg insulin/g of fibers, has been characterized in vitro by investigation of the desorption kinetics of the insulin from the fibrous depot. It has been shown that insulin is controllably released in quantities of 1.3-1.6 mg of insulin during 24 hours, in the course of 20 days. The results of biocompatibility tests have shown that the examined artificial depot neither shows irritating effects nor provokes sensitizing or cytotoxic effects. Therefore, these materials are acceptable for use in a direct contact with tissue of a living organism.",
publisher = "Korean Fiber Soc, Seoul",
journal = "Fibers and Polymers",
title = "Oxidized Cotton as a Substrate for the Preparation of Hormone-Active Fibers-Characterization, Efficiency and Biocompatibility",
pages = "1004-997",
number = "5",
volume = "16",
doi = "10.1007/s12221-015-0997-6"
}

Pejić, B., Medović-Baralić, A., Kojić, Z., Škundrić, P.,& Kostić, M.. (2015). Oxidized Cotton as a Substrate for the Preparation of Hormone-Active Fibers-Characterization, Efficiency and Biocompatibility. in Fibers and Polymers
Korean Fiber Soc, Seoul., 16(5), 997-1004.
https://doi.org/10.1007/s12221-015-0997-6

Pejić B, Medović-Baralić A, Kojić Z, Škundrić P, Kostić M. Oxidized Cotton as a Substrate for the Preparation of Hormone-Active Fibers-Characterization, Efficiency and Biocompatibility. in Fibers and Polymers. 2015;16(5):997-1004.
doi:10.1007/s12221-015-0997-6 .

Pejić, Biljana, Medović-Baralić, Adela, Kojić, Zvezdana, Škundrić, Petar, Kostić, Mirjana, "Oxidized Cotton as a Substrate for the Preparation of Hormone-Active Fibers-Characterization, Efficiency and Biocompatibility" in Fibers and Polymers, 16, no. 5 (2015):997-1004,
https://doi.org/10.1007/s12221-015-0997-6 . .

TY  - JOUR
AU  - Veljović, Đorđe
AU  - Čolić, Miodrag
AU  - Kojić, Vesna
AU  - Bogdanović, Gordana
AU  - Kojić, Zvezdana
AU  - Banjac, Andrijana
AU  - Palcevskis, Eriks
AU  - Petrović, Rada
AU  - Janaćković, Đorđe
PY  - 2012
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/2174
AB  - The effect of decreasing the grain size on the biocompatibility, cellmaterial interface, and mechanical properties of microwave-sintered monophase hydroxyapatite bioceramics was investigated in this study. A nanosized stoichiometric hydroxyapatite powder was isostatically pressed at high pressure and sintered in a microwave furnace in order to obtain fine grained dense bioceramics. The samples sintered at 1200 degrees C, with a density near the theoretical one, were composed of micron-sized grains, while the grain size decreased to 130 nm on decreasing the sintering temperature to 900 degrees C. This decrease in the grain size certainly led to increases in the fracture toughness by much as 54%. An in vitro investigation of biocompatibility with L929 and human MRC-5 fibroblast cells showed noncytotoxic effects for both types of bioceramics, while the relative cell proliferation rate, cell attachment and metabolic activity of the fibroblasts were improved with decreasing of grain size. An initial in vivo investigation of biocompatibility by the primary cutaneous irritation test showed that both materials exhibited no irritation properties.
PB  - Wiley, Hoboken
T2  - Journal of Biomedical Materials Research Part A
T1  - The effect of grain size on the biocompatibility, cell-materials interface, and mechanical properties of microwave-sintered bioceramics
EP  - 3070
IS  - 11
SP  - 3059
VL  - 100A
DO  - 10.1002/jbm.a.34225
ER  - 

@article{
author = "Veljović, Đorđe and Čolić, Miodrag and Kojić, Vesna and Bogdanović, Gordana and Kojić, Zvezdana and Banjac, Andrijana and Palcevskis, Eriks and Petrović, Rada and Janaćković, Đorđe",
year = "2012",
abstract = "The effect of decreasing the grain size on the biocompatibility, cellmaterial interface, and mechanical properties of microwave-sintered monophase hydroxyapatite bioceramics was investigated in this study. A nanosized stoichiometric hydroxyapatite powder was isostatically pressed at high pressure and sintered in a microwave furnace in order to obtain fine grained dense bioceramics. The samples sintered at 1200 degrees C, with a density near the theoretical one, were composed of micron-sized grains, while the grain size decreased to 130 nm on decreasing the sintering temperature to 900 degrees C. This decrease in the grain size certainly led to increases in the fracture toughness by much as 54%. An in vitro investigation of biocompatibility with L929 and human MRC-5 fibroblast cells showed noncytotoxic effects for both types of bioceramics, while the relative cell proliferation rate, cell attachment and metabolic activity of the fibroblasts were improved with decreasing of grain size. An initial in vivo investigation of biocompatibility by the primary cutaneous irritation test showed that both materials exhibited no irritation properties.",
publisher = "Wiley, Hoboken",
journal = "Journal of Biomedical Materials Research Part A",
title = "The effect of grain size on the biocompatibility, cell-materials interface, and mechanical properties of microwave-sintered bioceramics",
pages = "3070-3059",
number = "11",
volume = "100A",
doi = "10.1002/jbm.a.34225"
}

Veljović, Đ., Čolić, M., Kojić, V., Bogdanović, G., Kojić, Z., Banjac, A., Palcevskis, E., Petrović, R.,& Janaćković, Đ.. (2012). The effect of grain size on the biocompatibility, cell-materials interface, and mechanical properties of microwave-sintered bioceramics. in Journal of Biomedical Materials Research Part A
Wiley, Hoboken., 100A(11), 3059-3070.
https://doi.org/10.1002/jbm.a.34225

Veljović Đ, Čolić M, Kojić V, Bogdanović G, Kojić Z, Banjac A, Palcevskis E, Petrović R, Janaćković Đ. The effect of grain size on the biocompatibility, cell-materials interface, and mechanical properties of microwave-sintered bioceramics. in Journal of Biomedical Materials Research Part A. 2012;100A(11):3059-3070.
doi:10.1002/jbm.a.34225 .

Veljović, Đorđe, Čolić, Miodrag, Kojić, Vesna, Bogdanović, Gordana, Kojić, Zvezdana, Banjac, Andrijana, Palcevskis, Eriks, Petrović, Rada, Janaćković, Đorđe, "The effect of grain size on the biocompatibility, cell-materials interface, and mechanical properties of microwave-sintered bioceramics" in Journal of Biomedical Materials Research Part A, 100A, no. 11 (2012):3059-3070,
https://doi.org/10.1002/jbm.a.34225 . .

TY  - JOUR
AU  - Kojić, Zvezdana
AU  - Stojanović, D.
AU  - Popadić, S.
AU  - Jokanović, M.
AU  - Janaćković, Đorđe
PY  - 2009
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/1355
AB  - The aim of this study was to assess the irritant properties of a new developed calcium phosphate ceramic, α-tricalcium phosphate (α-TCP) after single application to intact skin of the rabbit. The test substance, α-TCP was produced by modified hydrothermal method and prepared in two different forms, as a solid material (disc 5 x 2 mm) and paste. Both, solid material and paste of α-TCP were evaluated for primary skin irritation to the ISO 10993-10:2002/Amd 1:2006 Biological Evaluation of Medical Devices - Part 10. At the end of the study macroscopic examination of the skin was performed. In this model, general and local tolerances were good. Score of primary irritation (SPI) and primary irritation index (PII) of α-TCP for both, solid material and paste, revealed that there was no significant toxicity/irritability (PII = 0.0) as compared to the negative control (PII = 0.0). Positive control did cause significant skin irritation in acute irritation test using Draize technique in rabbit model (PII = 2.11). Based on present results, it can be concluded that the the irritation potential of the tested material is negligible. However, other procedures for preclinical safety assessments of the α-TCP material are needed in order to completely elucidate its toxic potential.
PB  - General Physiol And Biophysics, Bratislava
T2  - General Physiology and Biophysics
T1  - The irritative property of α-tricalcium phosphate to the rabbit skin
EP  - 173
IS  - SPECIAL ISSUES
SP  - 168
VL  - 28
DO  - 10.4149/gpb_2009_02_168
ER  - 

@article{
author = "Kojić, Zvezdana and Stojanović, D. and Popadić, S. and Jokanović, M. and Janaćković, Đorđe",
year = "2009",
abstract = "The aim of this study was to assess the irritant properties of a new developed calcium phosphate ceramic, α-tricalcium phosphate (α-TCP) after single application to intact skin of the rabbit. The test substance, α-TCP was produced by modified hydrothermal method and prepared in two different forms, as a solid material (disc 5 x 2 mm) and paste. Both, solid material and paste of α-TCP were evaluated for primary skin irritation to the ISO 10993-10:2002/Amd 1:2006 Biological Evaluation of Medical Devices - Part 10. At the end of the study macroscopic examination of the skin was performed. In this model, general and local tolerances were good. Score of primary irritation (SPI) and primary irritation index (PII) of α-TCP for both, solid material and paste, revealed that there was no significant toxicity/irritability (PII = 0.0) as compared to the negative control (PII = 0.0). Positive control did cause significant skin irritation in acute irritation test using Draize technique in rabbit model (PII = 2.11). Based on present results, it can be concluded that the the irritation potential of the tested material is negligible. However, other procedures for preclinical safety assessments of the α-TCP material are needed in order to completely elucidate its toxic potential.",
publisher = "General Physiol And Biophysics, Bratislava",
journal = "General Physiology and Biophysics",
title = "The irritative property of α-tricalcium phosphate to the rabbit skin",
pages = "173-168",
number = "SPECIAL ISSUES",
volume = "28",
doi = "10.4149/gpb_2009_02_168"
}

Kojić, Z., Stojanović, D., Popadić, S., Jokanović, M.,& Janaćković, Đ.. (2009). The irritative property of α-tricalcium phosphate to the rabbit skin. in General Physiology and Biophysics
General Physiol And Biophysics, Bratislava., 28(SPECIAL ISSUES), 168-173.
https://doi.org/10.4149/gpb_2009_02_168

Kojić Z, Stojanović D, Popadić S, Jokanović M, Janaćković Đ. The irritative property of α-tricalcium phosphate to the rabbit skin. in General Physiology and Biophysics. 2009;28(SPECIAL ISSUES):168-173.
doi:10.4149/gpb_2009_02_168 .

Kojić, Zvezdana, Stojanović, D., Popadić, S., Jokanović, M., Janaćković, Đorđe, "The irritative property of α-tricalcium phosphate to the rabbit skin" in General Physiology and Biophysics, 28, no. SPECIAL ISSUES (2009):168-173,
https://doi.org/10.4149/gpb_2009_02_168 . .

TY  - JOUR
AU  - Marković, Danica
AU  - Kojić, Zvezdana
AU  - Marinković, D.
AU  - Danilović, Vesna
AU  - Radovanović, Anita
AU  - Janaćković, Đorđe
PY  - 2009
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/1497
AB  - The purpose of this study was to evaluate the tissue response induced by bioceramical materials (BCM) implanted in rat subcutaneous tissue. Thirty two rats were assigned to 6 groups, as following: control group i.e. not treated; dental ceramic (DC) implants; alfa tricalcium phosphate synthetised at 22 MPa (αTCP22) and at 45 MPa (αTCP45); hydroxyapatite synthetised at 22 MPa (HAP22) and at 45 MPa (HAP45). Contra lateral sides of all test animals represented the blank control surgically incisied at the paravertebral sockets. The experimental groups received subcutaneous implants of the test BCM materials. Samples were collected after 14 days and processed histologically. Inflammatory reactions were noted microscopically. The inflammatory infiltrate consisted of lymphocytes, polimorphonuclears, macrophages and mastocytes. At same time there were signs of increased fibrosis around the graft places. In conclusion, the implant sides compared with surgical incision wounds induced a foreign body-type granuloma with subsequent fibrosis around the grafts. The presence of a capsule at the interface with BCM in rat subcutis did not elicit any remarkable immune responses, thus being considered biocompatible. By evaluating different responses according to BCM, the most intense tissue reaction was noticed at HAP45, graded as severe, and mild to moderate for DC, HAP22 and alfa tricaltium phosphate.
AB  - Svrha ove studije je bila procena tkivnog odgovora indukovanog biokeramič kim materijalima (BCM) inplantiranim u subkutano tkivo pacova. Trideset dva pacova je bilo podeljeno u sledećih 6 grupa: kontrolna grupa-neoperisana; inplantirane sa: dentalnom keramikom (DC); alfa trikalcijum fosfatima sintetisanim na 22 MPa (αTCP22) i na 45 MPa (αTCP45); hidroksiapatitom sintetisanim na 22 MPa (HAP22) i na 45 MPa (HAP45). Kontralateralne strane svih životinja bile su slepa kontrola i urađene su kao džepovi hirurške incizije u subkutanom tkivu. Eksperimentalne grupe su imale subkutano inplantirane biokeramičke materijale. Uzorci su sakupljeni posle 14 dana i sprovedeni u histološkoj proceduri, a inflamatorna reakcija je praćena mikroskopski. Inflamatorni infiltrat se sastojao od limfocita, polimorfonuklearnih leukocita, makrofaga i mastocita. Istovremeno su uočeni znaci rastuće fibroze oko mesta graftova. Inplantirana mesta u poređenju sa hirurškim ranama indukuju granulom karakterističnog tipa na strano telo sa posledičnom fibrozom oko graftova, kapsulom na dodirnoj površini sa BCM u subkutisu pacova, ne izazivajući uočljivu imunološ ku reakciju, tako da odgovor tkiva ukazuje na biokompatibilnost. Procenjivanjem odgovora sa različitim BCM, zabeležena je najintenzivnija (snažna) tkivna reakcija kod HAP45 inplanta, a blaga do umerena kod DC, HAP22 i alfa trikalcijumfosfata.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta Veterinaria, Beograd
T1  - Histological and immunohistochemical evaluations of rat soft tissue response to bioceramical implants
T1  - Histološka i imunohistohemijska procena reakcije mekog tkiva pacova na biokeramičke implante
EP  - 253
IS  - 2-3
SP  - 243
VL  - 59
DO  - 10.2298/AVB0903243M
ER  - 

@article{
author = "Marković, Danica and Kojić, Zvezdana and Marinković, D. and Danilović, Vesna and Radovanović, Anita and Janaćković, Đorđe",
year = "2009",
abstract = "The purpose of this study was to evaluate the tissue response induced by bioceramical materials (BCM) implanted in rat subcutaneous tissue. Thirty two rats were assigned to 6 groups, as following: control group i.e. not treated; dental ceramic (DC) implants; alfa tricalcium phosphate synthetised at 22 MPa (αTCP22) and at 45 MPa (αTCP45); hydroxyapatite synthetised at 22 MPa (HAP22) and at 45 MPa (HAP45). Contra lateral sides of all test animals represented the blank control surgically incisied at the paravertebral sockets. The experimental groups received subcutaneous implants of the test BCM materials. Samples were collected after 14 days and processed histologically. Inflammatory reactions were noted microscopically. The inflammatory infiltrate consisted of lymphocytes, polimorphonuclears, macrophages and mastocytes. At same time there were signs of increased fibrosis around the graft places. In conclusion, the implant sides compared with surgical incision wounds induced a foreign body-type granuloma with subsequent fibrosis around the grafts. The presence of a capsule at the interface with BCM in rat subcutis did not elicit any remarkable immune responses, thus being considered biocompatible. By evaluating different responses according to BCM, the most intense tissue reaction was noticed at HAP45, graded as severe, and mild to moderate for DC, HAP22 and alfa tricaltium phosphate., Svrha ove studije je bila procena tkivnog odgovora indukovanog biokeramič kim materijalima (BCM) inplantiranim u subkutano tkivo pacova. Trideset dva pacova je bilo podeljeno u sledećih 6 grupa: kontrolna grupa-neoperisana; inplantirane sa: dentalnom keramikom (DC); alfa trikalcijum fosfatima sintetisanim na 22 MPa (αTCP22) i na 45 MPa (αTCP45); hidroksiapatitom sintetisanim na 22 MPa (HAP22) i na 45 MPa (HAP45). Kontralateralne strane svih životinja bile su slepa kontrola i urađene su kao džepovi hirurške incizije u subkutanom tkivu. Eksperimentalne grupe su imale subkutano inplantirane biokeramičke materijale. Uzorci su sakupljeni posle 14 dana i sprovedeni u histološkoj proceduri, a inflamatorna reakcija je praćena mikroskopski. Inflamatorni infiltrat se sastojao od limfocita, polimorfonuklearnih leukocita, makrofaga i mastocita. Istovremeno su uočeni znaci rastuće fibroze oko mesta graftova. Inplantirana mesta u poređenju sa hirurškim ranama indukuju granulom karakterističnog tipa na strano telo sa posledičnom fibrozom oko graftova, kapsulom na dodirnoj površini sa BCM u subkutisu pacova, ne izazivajući uočljivu imunološ ku reakciju, tako da odgovor tkiva ukazuje na biokompatibilnost. Procenjivanjem odgovora sa različitim BCM, zabeležena je najintenzivnija (snažna) tkivna reakcija kod HAP45 inplanta, a blaga do umerena kod DC, HAP22 i alfa trikalcijumfosfata.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta Veterinaria, Beograd",
title = "Histological and immunohistochemical evaluations of rat soft tissue response to bioceramical implants, Histološka i imunohistohemijska procena reakcije mekog tkiva pacova na biokeramičke implante",
pages = "253-243",
number = "2-3",
volume = "59",
doi = "10.2298/AVB0903243M"
}

Marković, D., Kojić, Z., Marinković, D., Danilović, V., Radovanović, A.,& Janaćković, Đ.. (2009). Histological and immunohistochemical evaluations of rat soft tissue response to bioceramical implants. in Acta Veterinaria, Beograd
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 59(2-3), 243-253.
https://doi.org/10.2298/AVB0903243M

Marković D, Kojić Z, Marinković D, Danilović V, Radovanović A, Janaćković Đ. Histological and immunohistochemical evaluations of rat soft tissue response to bioceramical implants. in Acta Veterinaria, Beograd. 2009;59(2-3):243-253.
doi:10.2298/AVB0903243M .

Marković, Danica, Kojić, Zvezdana, Marinković, D., Danilović, Vesna, Radovanović, Anita, Janaćković, Đorđe, "Histological and immunohistochemical evaluations of rat soft tissue response to bioceramical implants" in Acta Veterinaria, Beograd, 59, no. 2-3 (2009):243-253,
https://doi.org/10.2298/AVB0903243M . .

TY  - JOUR
AU  - Kojić, Zvezdana
AU  - Janaćković, Đorđe
AU  - Stojanović, Dobrica
AU  - Veljović, Đorđe
AU  - Jokić, Bojan
PY  - 2009
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/1444
AB  - Objectives. The aim of this study was to determine the irritant properties of alpha-tricalcium phosphate, a new calcium phosphate ceramic material, after single application to intact skin of the rabbit. Methods. As a starting compound for obtaining α-tricalcium phosphate, calcium hydroxyapatite was used, sintered and hot pressed. The material was prepared and tested as solid material and paste. The material was evaluated for primary skin irritation according to the UNI EN ISO 10993-10:2002 /Amd 1:2006 Biological evaluation of medical devices, Part 10: Tests for irritation and delayed-type hypersensitivity. The back of the animals was clipped free of fur and divided into four sites with the same area 24 hours before application of the sample. The material was applied to only two sites; the other two were used as controls. All the sites were covered by gauze and the back of the rabbit was wrapped with a non-occlusive bandage. After 4 hours, the bandage and the test material were removed; 1 hour later the sites were examined for skin irritation and the observation was repeated after 24, 48 and 72 hours. The Score of Primary Irritation (SPI) was calculated for each animal and the Primary Irritation Index (PII) was calculated as the arithmetical mean of SPI values. Results. The PII of the test material resulted 0.0. Conclusion. Based on present results, it can be concluded that the primary skinirritation of alpha-tricalcium phosphate tested can be considered negligible.
AB  - Cilj istraživanja: Odrediti iritativna svojstva alfa-trikalcijum fosfara (novorazvijenog biomaterijala na bazi kalcijum fosfatne keramike) u toku njegove jednokratne primene na intaktnu kožu kunica. Materijal i metode: Za dobijanje alfa-trikalcijum fosfara (alfa-TCP) korišćen je kalcijum-hidroksiapatit, koji je sinterovan i toplo presovan. Materijal je pripremljen i testiran u cvrstom obliku i u obliku paste. Prema preporukama međunarodnih standarda za ispitivanje biokompatibilnosti (ISO 10993-10:2002/ Amd 1: 2006 Biološko ispitivanje medicinske opreme, deo 10: testovi iritacije i odložene reakcije hipersenzitivnosti) iritativna svojstva određena su u testu primarne kutane iritacije. Krzno na leđima kunića (novozelanski beli kunići, n=12) obrijano je 24 h pre aplikovanja test materijala, a koža je šematski podeljena u četiri zone. Testirani alfa-TCP je primenjen na samo dva mesta, dok su druga dva mesta na istoj životinji korišćena kao negativne kontrole. Delovi kože tretirani mlečnom kiselinom (98%) korišćeni su kao pozitivna kontrola a posebnu kontrolu je činio tretman Na2HPO4 (korišćen za pripremanje paste), fednokratni kontakt kože i ispitivanog materijala trajao je 4 sata, nakon čega je materijal uklonjen, a 1 sat kasnije, makro-patološki određena je iritacija kože. Ispitivanje iritacije kože ponovljeno je nakon 24h, 48 h i 72 h. Izračunavani su skor primarne kutane iritacije (SPP) i indeks primarne kutane iritacije (PII). Rezultati: Indeks primarne kutane iritacije za alfa-TCP u čvrstom obliku i u obliku paste bio je nula i nije se statistički razlikovao u odnosu na negativnu kontrolu (p gt 0.05). Zaključak: Na osnovu dobijenih rezultata može se zaključiti da novorazvijeni biomaterijal, modifikovani alfa-trikalcijum fosfat, u čvrstom obliku i u obliku paste, ne ispoljava iritirajuća svojstva.
PB  - Univerzitet u Beogradu - Medicinski fakultet, Beograd
T2  - Medicinska istraživanja
T1  - Investigation of biocompatibility of alpha-tricalcium phosphate: Test for primary cutaneous irritation
T1  - Ispitivanje biokompatibilnosti alfa-trikalcijum fosfata - test primarne kutane iritacije
EP  - 27
IS  - 1
SP  - 21
VL  - 43
UR  - https://hdl.handle.net/21.15107/rcub_technorep_1444
ER  - 

@article{
author = "Kojić, Zvezdana and Janaćković, Đorđe and Stojanović, Dobrica and Veljović, Đorđe and Jokić, Bojan",
year = "2009",
abstract = "Objectives. The aim of this study was to determine the irritant properties of alpha-tricalcium phosphate, a new calcium phosphate ceramic material, after single application to intact skin of the rabbit. Methods. As a starting compound for obtaining α-tricalcium phosphate, calcium hydroxyapatite was used, sintered and hot pressed. The material was prepared and tested as solid material and paste. The material was evaluated for primary skin irritation according to the UNI EN ISO 10993-10:2002 /Amd 1:2006 Biological evaluation of medical devices, Part 10: Tests for irritation and delayed-type hypersensitivity. The back of the animals was clipped free of fur and divided into four sites with the same area 24 hours before application of the sample. The material was applied to only two sites; the other two were used as controls. All the sites were covered by gauze and the back of the rabbit was wrapped with a non-occlusive bandage. After 4 hours, the bandage and the test material were removed; 1 hour later the sites were examined for skin irritation and the observation was repeated after 24, 48 and 72 hours. The Score of Primary Irritation (SPI) was calculated for each animal and the Primary Irritation Index (PII) was calculated as the arithmetical mean of SPI values. Results. The PII of the test material resulted 0.0. Conclusion. Based on present results, it can be concluded that the primary skinirritation of alpha-tricalcium phosphate tested can be considered negligible., Cilj istraživanja: Odrediti iritativna svojstva alfa-trikalcijum fosfara (novorazvijenog biomaterijala na bazi kalcijum fosfatne keramike) u toku njegove jednokratne primene na intaktnu kožu kunica. Materijal i metode: Za dobijanje alfa-trikalcijum fosfara (alfa-TCP) korišćen je kalcijum-hidroksiapatit, koji je sinterovan i toplo presovan. Materijal je pripremljen i testiran u cvrstom obliku i u obliku paste. Prema preporukama međunarodnih standarda za ispitivanje biokompatibilnosti (ISO 10993-10:2002/ Amd 1: 2006 Biološko ispitivanje medicinske opreme, deo 10: testovi iritacije i odložene reakcije hipersenzitivnosti) iritativna svojstva određena su u testu primarne kutane iritacije. Krzno na leđima kunića (novozelanski beli kunići, n=12) obrijano je 24 h pre aplikovanja test materijala, a koža je šematski podeljena u četiri zone. Testirani alfa-TCP je primenjen na samo dva mesta, dok su druga dva mesta na istoj životinji korišćena kao negativne kontrole. Delovi kože tretirani mlečnom kiselinom (98%) korišćeni su kao pozitivna kontrola a posebnu kontrolu je činio tretman Na2HPO4 (korišćen za pripremanje paste), fednokratni kontakt kože i ispitivanog materijala trajao je 4 sata, nakon čega je materijal uklonjen, a 1 sat kasnije, makro-patološki određena je iritacija kože. Ispitivanje iritacije kože ponovljeno je nakon 24h, 48 h i 72 h. Izračunavani su skor primarne kutane iritacije (SPP) i indeks primarne kutane iritacije (PII). Rezultati: Indeks primarne kutane iritacije za alfa-TCP u čvrstom obliku i u obliku paste bio je nula i nije se statistički razlikovao u odnosu na negativnu kontrolu (p gt 0.05). Zaključak: Na osnovu dobijenih rezultata može se zaključiti da novorazvijeni biomaterijal, modifikovani alfa-trikalcijum fosfat, u čvrstom obliku i u obliku paste, ne ispoljava iritirajuća svojstva.",
publisher = "Univerzitet u Beogradu - Medicinski fakultet, Beograd",
journal = "Medicinska istraživanja",
title = "Investigation of biocompatibility of alpha-tricalcium phosphate: Test for primary cutaneous irritation, Ispitivanje biokompatibilnosti alfa-trikalcijum fosfata - test primarne kutane iritacije",
pages = "27-21",
number = "1",
volume = "43",
url = "https://hdl.handle.net/21.15107/rcub_technorep_1444"
}

Kojić, Z., Janaćković, Đ., Stojanović, D., Veljović, Đ.,& Jokić, B.. (2009). Investigation of biocompatibility of alpha-tricalcium phosphate: Test for primary cutaneous irritation. in Medicinska istraživanja
Univerzitet u Beogradu - Medicinski fakultet, Beograd., 43(1), 21-27.
https://hdl.handle.net/21.15107/rcub_technorep_1444

Kojić Z, Janaćković Đ, Stojanović D, Veljović Đ, Jokić B. Investigation of biocompatibility of alpha-tricalcium phosphate: Test for primary cutaneous irritation. in Medicinska istraživanja. 2009;43(1):21-27.
https://hdl.handle.net/21.15107/rcub_technorep_1444 .

Kojić, Zvezdana, Janaćković, Đorđe, Stojanović, Dobrica, Veljović, Đorđe, Jokić, Bojan, "Investigation of biocompatibility of alpha-tricalcium phosphate: Test for primary cutaneous irritation" in Medicinska istraživanja, 43, no. 1 (2009):21-27,
https://hdl.handle.net/21.15107/rcub_technorep_1444 .

TY  - JOUR
AU  - Stojanović, D.
AU  - Janaćković, Đorđe
AU  - Marković, Danica
AU  - Tasić, Goran
AU  - Aleksandrić, B.
AU  - Kojić, Zvezdana
PY  - 2008
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/1255
AB  - Calcium phosphate ceramics are among the more commonly used and biocompatible ceramics. Recently, we have synthesized a new calcium phosphate ceramic, alpha tricalcium phosphate (aTCP). The aim of this study was to assess the biocompatibility of this original, in our laboratory modified, newly synthesized aTCP ceramic, by carefully evaluating the inflammatory reaction of soft tissue in response to its subcutaneous implantation, and by comparing this result with the results of already widely used virtually non-toxic, non-immunogenic, and almost chemically inert dental (DC) and hydroxy apatite (HAP) ceramics. Implants (diameter 5x2 mm) of aTCP, DC and HAP were implanted into 12 adult male rats subcutaneously. At 2 weeks and 12 weeks post-implantation, the animals were euthanized and the tissueimplant reactions were analyzed histologically. Evaluation of routine stained sections (5 μm, hematoxylin & eosin) of the cutis and subcutis surrounding the aTCP, DC and HAP ceramics revealed the following: 1) all the ceramic devices had fibrous connective tissue capsules; 2) there were significant differences in the tissue - implant reactions based on the estimated time, while there were no differences in the tissue-implant reaction based on the type of ceramic material; 3) two weeks after implantation hyperemia and cellular proliferation were the most expressive results, while twelve weeks after implantation extensive angiogenesis and collagen fibers production were the prominent findings for all types of implanted calcium phosphate ceramics.
AB  - Podaci iz literature ukazuju da se kalcijum fosfatna keramika ubraja među najčešće korišćene i biološki najkompatibilnije keramičke materijale koji se danas primenjuju u medicini. U našoj laboratoriji sintetisana je nova vrsta kalcijum fosfatne keramike, alfa-trikalcijum fosfat (aTCP). Cilj ovog rada je bio da se proceni biokompatibilnost ovog, modifikovanog, novosintetisanog aTCP, putem pažljive procene inflamatorne reakcije mekog tkiva koja nastaje kao odgovor na njegovu subkutanu implantaciju i putem upoređivanja ovih rezultata sa rezultatima subku- tane implantacije dentalne keramike (DC) i hidroksiapatita (HAP), koji su ne-toksični, ne-imunogeni i skoro hemijski potpuno inertni. Kod 12 odraslih mužjaka Wistar pacova implantirani su subkutano implanti aTCP, DC i HAP (disk 5x2 mm). Na kraju 2. i 12. nedelje nakon implantacije, životinje su žrtvovane i reakcija tkivoimplant je analizirana histološki. Analiza rutinski obojenih (5 μm, hemotoksilin & eozin) isečaka tkiva kutisa i subkutisa koje se nalazilo oko implantiranog aTCP, DC i HAP, otkrila je sledeće: 1) svi keramički implanti bili su okruženi fibroznom kapsulom; 2) u odnosu na vreme posle implantacije, postojale su značajne razlike u tkivo-implant reakciji, dok u odnosu na vrstu keramičkog materijala, nisu postojale razlike u reakciji tkiva na implant; 3) za sve tri vrste implantirane kalcijum-fosfatne keramike, glavni nalaz u tkivu bio je, dve nedelje nakon implantacije, hiperemija i ćelijska infiltracija, dok nakon 12 nedelja prisutna intenzivna angiogeneza i stvaranje kolagenih vlakana.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta Veterinaria, Beograd
T1  - A tissue-implant reaction associated with subcutan implantation of alpha-tricalcium phosphate, dental ceramic and hydroxyapatite bioceramics in rats
T1  - Tkivo-implant reakcija povezana sa subkutanom implantacijom alfa-trikalcijum fosfata, dentalne keramike i hidroksiapatit biokeramike kod pacova
EP  - 393
IS  - 4
SP  - 381
VL  - 58
DO  - 10.2298/AVB0804381S
ER  - 

@article{
author = "Stojanović, D. and Janaćković, Đorđe and Marković, Danica and Tasić, Goran and Aleksandrić, B. and Kojić, Zvezdana",
year = "2008",
abstract = "Calcium phosphate ceramics are among the more commonly used and biocompatible ceramics. Recently, we have synthesized a new calcium phosphate ceramic, alpha tricalcium phosphate (aTCP). The aim of this study was to assess the biocompatibility of this original, in our laboratory modified, newly synthesized aTCP ceramic, by carefully evaluating the inflammatory reaction of soft tissue in response to its subcutaneous implantation, and by comparing this result with the results of already widely used virtually non-toxic, non-immunogenic, and almost chemically inert dental (DC) and hydroxy apatite (HAP) ceramics. Implants (diameter 5x2 mm) of aTCP, DC and HAP were implanted into 12 adult male rats subcutaneously. At 2 weeks and 12 weeks post-implantation, the animals were euthanized and the tissueimplant reactions were analyzed histologically. Evaluation of routine stained sections (5 μm, hematoxylin & eosin) of the cutis and subcutis surrounding the aTCP, DC and HAP ceramics revealed the following: 1) all the ceramic devices had fibrous connective tissue capsules; 2) there were significant differences in the tissue - implant reactions based on the estimated time, while there were no differences in the tissue-implant reaction based on the type of ceramic material; 3) two weeks after implantation hyperemia and cellular proliferation were the most expressive results, while twelve weeks after implantation extensive angiogenesis and collagen fibers production were the prominent findings for all types of implanted calcium phosphate ceramics., Podaci iz literature ukazuju da se kalcijum fosfatna keramika ubraja među najčešće korišćene i biološki najkompatibilnije keramičke materijale koji se danas primenjuju u medicini. U našoj laboratoriji sintetisana je nova vrsta kalcijum fosfatne keramike, alfa-trikalcijum fosfat (aTCP). Cilj ovog rada je bio da se proceni biokompatibilnost ovog, modifikovanog, novosintetisanog aTCP, putem pažljive procene inflamatorne reakcije mekog tkiva koja nastaje kao odgovor na njegovu subkutanu implantaciju i putem upoređivanja ovih rezultata sa rezultatima subku- tane implantacije dentalne keramike (DC) i hidroksiapatita (HAP), koji su ne-toksični, ne-imunogeni i skoro hemijski potpuno inertni. Kod 12 odraslih mužjaka Wistar pacova implantirani su subkutano implanti aTCP, DC i HAP (disk 5x2 mm). Na kraju 2. i 12. nedelje nakon implantacije, životinje su žrtvovane i reakcija tkivoimplant je analizirana histološki. Analiza rutinski obojenih (5 μm, hemotoksilin & eozin) isečaka tkiva kutisa i subkutisa koje se nalazilo oko implantiranog aTCP, DC i HAP, otkrila je sledeće: 1) svi keramički implanti bili su okruženi fibroznom kapsulom; 2) u odnosu na vreme posle implantacije, postojale su značajne razlike u tkivo-implant reakciji, dok u odnosu na vrstu keramičkog materijala, nisu postojale razlike u reakciji tkiva na implant; 3) za sve tri vrste implantirane kalcijum-fosfatne keramike, glavni nalaz u tkivu bio je, dve nedelje nakon implantacije, hiperemija i ćelijska infiltracija, dok nakon 12 nedelja prisutna intenzivna angiogeneza i stvaranje kolagenih vlakana.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta Veterinaria, Beograd",
title = "A tissue-implant reaction associated with subcutan implantation of alpha-tricalcium phosphate, dental ceramic and hydroxyapatite bioceramics in rats, Tkivo-implant reakcija povezana sa subkutanom implantacijom alfa-trikalcijum fosfata, dentalne keramike i hidroksiapatit biokeramike kod pacova",
pages = "393-381",
number = "4",
volume = "58",
doi = "10.2298/AVB0804381S"
}

Stojanović, D., Janaćković, Đ., Marković, D., Tasić, G., Aleksandrić, B.,& Kojić, Z.. (2008). A tissue-implant reaction associated with subcutan implantation of alpha-tricalcium phosphate, dental ceramic and hydroxyapatite bioceramics in rats. in Acta Veterinaria, Beograd
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 58(4), 381-393.
https://doi.org/10.2298/AVB0804381S

Stojanović D, Janaćković Đ, Marković D, Tasić G, Aleksandrić B, Kojić Z. A tissue-implant reaction associated with subcutan implantation of alpha-tricalcium phosphate, dental ceramic and hydroxyapatite bioceramics in rats. in Acta Veterinaria, Beograd. 2008;58(4):381-393.
doi:10.2298/AVB0804381S .

Stojanović, D., Janaćković, Đorđe, Marković, Danica, Tasić, Goran, Aleksandrić, B., Kojić, Zvezdana, "A tissue-implant reaction associated with subcutan implantation of alpha-tricalcium phosphate, dental ceramic and hydroxyapatite bioceramics in rats" in Acta Veterinaria, Beograd, 58, no. 4 (2008):381-393,
https://doi.org/10.2298/AVB0804381S . .

TY  - JOUR
AU  - Medović, Adela
AU  - Kojić, Zvezdana
AU  - Tasić, Goran
AU  - Milaković, Branko
AU  - Kostić, Mirjana
AU  - Škundrić, Petar
PY  - 2008
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/1263
AB  - In this paper an account of biocompatibility of a hormonactive fiber in the form of biologically active complex chitosan-insulin is presented. The behavior of artificial depots of insulin containing 180-330mg of insulin per gram of fiber has been studied. The artificial depot of insulin has been characterized from the standpoint of its behavior in physiological solution (in the culture of L929 cells and in organism of an experimental animal). In vitro conditions, the intensity of desorption depends on the nature of solution and on pH of medium. It has been shown that insulin is controllably delivered in physiological solutions in quantities of 1.3-1.6mg of insulin during 24 hours, at pH about 7. The quantity of insulin delivered has been assessed by UV Sprectrophotometry. Biocompatibility of hormone-active fibers in the form of artificial depot of insulin has been determined in pre-clinical conditions through determination of the degree of harmfulness (toxicity) to the organism of the experimental animal. Tests have been performed according to the matrix for testing of biocompatibility and according to recommendations and guides published in Guidelines ISO 10993. Noxiousness has been assessed by testing: citotoxicity, sensitivization and irritation. Qualitative and quantitative citotoxicity tests in direct contact on L929 cells culture have shown that a hormone-active fiber does not provoke the citotoxic effect. The results obtained have shown that quantities of controllably released insulin could satisfy basal needs of an organism and that the artificial depot does not show effects of toxicity. On the bases of the obtained results from tests and calculated index of sensitivitization it follows that the artificial depot of insulin does not cause sensitivization. Also, the results obtained by subcutaneous irritation testing showed that the fibrous artificial depot of insulin could be eveluated as a non-irritating bioactive material.
AB  - U ovom radu kao deo pretkliničkog ispitivanja biokompatibilnosti, ispitivana je toksičnost i efikasnost veštačkih depoa insulina. Veštački depoi insulina sadržali su 180-330 mg insulina po gramu vlakna hitozana. Cilj rada je bio: 1. odrediti kinetiku otpuštanja insulina iz hormonaktivnog vlakna u in vitro uslovima, 2. ispitati senzibilizaciju in vivo; 3. ispitati primarnu kutanu iritaciju in vivo i 4. ispitati citotoksični efekat in vitro. Metode: Količina otpuštenog insulina praćena je UV spektrofotometrijom. Pretklinička ispitivanja biokompatibilnosti hormonaktivnih vlakana izvršena su prema preporukama i vodičima publikovanih u Guidelines ISO 10993 kao i prema matriksu za ispitivanje biokompatibilnosti. Toksičnost je ispitana kroz testiranje: senzibilizacije i primarne kutane iritacije in vivo i testiranje citotoksičnosti (kvalitativno i kvantitativno) u kulturi L929 ćelija. Pokazano je da se insulin kontrolisano otpušta u fiziološkom rastvoru u količinama od 1.3-1.6 mg insulina u toku 24 sata, pri pH oko 7. Prema dobijenim rezultatima ispitivanja i izračunatog indeksa senzibilizcije sledi da veštački depo ne izaziva senzibilizaciju. Takođe, dobijeni rezultati ispitivanja primarne kutane iritacije su pokazali da se vlaknasti veštački depo insulina može oceniti kao neiritirajući bioaktivni materijal. Kvalitativni i kvantitativni testovi citotoksičnosti u direktnom kontaktu na kulturi ćelija L929 su pokazali da hormonaktivno vlakno ne izaziva citotoksični efekat. U cilju dalje karakterizacije biokompatibilnosti (toksičnosti i efikasnosti) hormonaktivnih polisahaidnih vlakana, dalja istraživanja su neophodna pre njihove kliničke primene.
PB  - Univerzitet u Beogradu - Medicinski fakultet, Beograd
T2  - Medicinska istraživanja
T1  - Toksičnost i kinetika otpuštanja insulina iz hormonaktivnih polisaharidnih vlakana
EP  - 22
IS  - 2
SP  - 17
VL  - 42
UR  - https://hdl.handle.net/21.15107/rcub_technorep_1263
ER  - 

@article{
author = "Medović, Adela and Kojić, Zvezdana and Tasić, Goran and Milaković, Branko and Kostić, Mirjana and Škundrić, Petar",
year = "2008",
abstract = "In this paper an account of biocompatibility of a hormonactive fiber in the form of biologically active complex chitosan-insulin is presented. The behavior of artificial depots of insulin containing 180-330mg of insulin per gram of fiber has been studied. The artificial depot of insulin has been characterized from the standpoint of its behavior in physiological solution (in the culture of L929 cells and in organism of an experimental animal). In vitro conditions, the intensity of desorption depends on the nature of solution and on pH of medium. It has been shown that insulin is controllably delivered in physiological solutions in quantities of 1.3-1.6mg of insulin during 24 hours, at pH about 7. The quantity of insulin delivered has been assessed by UV Sprectrophotometry. Biocompatibility of hormone-active fibers in the form of artificial depot of insulin has been determined in pre-clinical conditions through determination of the degree of harmfulness (toxicity) to the organism of the experimental animal. Tests have been performed according to the matrix for testing of biocompatibility and according to recommendations and guides published in Guidelines ISO 10993. Noxiousness has been assessed by testing: citotoxicity, sensitivization and irritation. Qualitative and quantitative citotoxicity tests in direct contact on L929 cells culture have shown that a hormone-active fiber does not provoke the citotoxic effect. The results obtained have shown that quantities of controllably released insulin could satisfy basal needs of an organism and that the artificial depot does not show effects of toxicity. On the bases of the obtained results from tests and calculated index of sensitivitization it follows that the artificial depot of insulin does not cause sensitivization. Also, the results obtained by subcutaneous irritation testing showed that the fibrous artificial depot of insulin could be eveluated as a non-irritating bioactive material., U ovom radu kao deo pretkliničkog ispitivanja biokompatibilnosti, ispitivana je toksičnost i efikasnost veštačkih depoa insulina. Veštački depoi insulina sadržali su 180-330 mg insulina po gramu vlakna hitozana. Cilj rada je bio: 1. odrediti kinetiku otpuštanja insulina iz hormonaktivnog vlakna u in vitro uslovima, 2. ispitati senzibilizaciju in vivo; 3. ispitati primarnu kutanu iritaciju in vivo i 4. ispitati citotoksični efekat in vitro. Metode: Količina otpuštenog insulina praćena je UV spektrofotometrijom. Pretklinička ispitivanja biokompatibilnosti hormonaktivnih vlakana izvršena su prema preporukama i vodičima publikovanih u Guidelines ISO 10993 kao i prema matriksu za ispitivanje biokompatibilnosti. Toksičnost je ispitana kroz testiranje: senzibilizacije i primarne kutane iritacije in vivo i testiranje citotoksičnosti (kvalitativno i kvantitativno) u kulturi L929 ćelija. Pokazano je da se insulin kontrolisano otpušta u fiziološkom rastvoru u količinama od 1.3-1.6 mg insulina u toku 24 sata, pri pH oko 7. Prema dobijenim rezultatima ispitivanja i izračunatog indeksa senzibilizcije sledi da veštački depo ne izaziva senzibilizaciju. Takođe, dobijeni rezultati ispitivanja primarne kutane iritacije su pokazali da se vlaknasti veštački depo insulina može oceniti kao neiritirajući bioaktivni materijal. Kvalitativni i kvantitativni testovi citotoksičnosti u direktnom kontaktu na kulturi ćelija L929 su pokazali da hormonaktivno vlakno ne izaziva citotoksični efekat. U cilju dalje karakterizacije biokompatibilnosti (toksičnosti i efikasnosti) hormonaktivnih polisahaidnih vlakana, dalja istraživanja su neophodna pre njihove kliničke primene.",
publisher = "Univerzitet u Beogradu - Medicinski fakultet, Beograd",
journal = "Medicinska istraživanja",
title = "Toksičnost i kinetika otpuštanja insulina iz hormonaktivnih polisaharidnih vlakana",
pages = "22-17",
number = "2",
volume = "42",
url = "https://hdl.handle.net/21.15107/rcub_technorep_1263"
}

Medović, A., Kojić, Z., Tasić, G., Milaković, B., Kostić, M.,& Škundrić, P.. (2008). Toksičnost i kinetika otpuštanja insulina iz hormonaktivnih polisaharidnih vlakana. in Medicinska istraživanja
Univerzitet u Beogradu - Medicinski fakultet, Beograd., 42(2), 17-22.
https://hdl.handle.net/21.15107/rcub_technorep_1263

Medović A, Kojić Z, Tasić G, Milaković B, Kostić M, Škundrić P. Toksičnost i kinetika otpuštanja insulina iz hormonaktivnih polisaharidnih vlakana. in Medicinska istraživanja. 2008;42(2):17-22.
https://hdl.handle.net/21.15107/rcub_technorep_1263 .

Medović, Adela, Kojić, Zvezdana, Tasić, Goran, Milaković, Branko, Kostić, Mirjana, Škundrić, Petar, "Toksičnost i kinetika otpuštanja insulina iz hormonaktivnih polisaharidnih vlakana" in Medicinska istraživanja, 42, no. 2 (2008):17-22,
https://hdl.handle.net/21.15107/rcub_technorep_1263 .