TY  - JOUR
AU  - Martin, Ivan
AU  - Obradović, Bojana
AU  - Treppo, S
AU  - Grodzinsky, AJ
AU  - Langer, R
AU  - Freed, LE
AU  - Vunjak-Novaković, Gordana
PY  - 2000
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/298
AB  - Cartilaginous constructs have been grown in vitro using chondrocytes, biodegradable polymer scaffolds, and tissue culture bioreactors. In the present work, we studied how the composition and mechanical properties of engineered cartilage can be modulated by the conditions and duration of in vitro cultivation, using three different environments: static flasks, mixed flasks, and rotating vessels. After 4-6 weeks, static culture yielded small and fragile constructs, while turbulent flow in mixed flasks induced the formation of an outer fibrous capsule; both environments resulted in constructs with poor mechanical properties. The constructs that were cultured freely suspended in a dynamic laminar flow field in rotating vessels had the highest fractions of glycosaminoglycans and collagen (respectively 75% and 39% of levels measured in native cartilage), and the best mechanical properties (equilibrium modulus, hydraulic permeability, dynamic stiffness, and streaming potential were all about 20% of values measured in native cartilage). Chondrocytes in cartilaginous constructs remained metabolically active and phenotypically stable over prolonged cultivation in rotating bioreactors. The wet weight fraction of glycosaminoglycans and equilibrium modulus of 7 month constructs reached or exceeded the corresponding values measured from freshly explanted native cartilage. Taken together, these findings suggest that functional equivalents of native cartilage can be engineered by optimizing the hydrodynamic conditions in tissue culture bioreactors and the duration of tissue cultivation.
PB  - IOS Press, Amsterdam
T2  - Biorheology
T1  - Modulation of the mechanical properties of tissue engineered cartilage
EP  - 147
IS  - 1-2
SP  - 141
VL  - 37
UR  - https://hdl.handle.net/21.15107/rcub_technorep_298
ER  - 

@article{
author = "Martin, Ivan and Obradović, Bojana and Treppo, S and Grodzinsky, AJ and Langer, R and Freed, LE and Vunjak-Novaković, Gordana",
year = "2000",
abstract = "Cartilaginous constructs have been grown in vitro using chondrocytes, biodegradable polymer scaffolds, and tissue culture bioreactors. In the present work, we studied how the composition and mechanical properties of engineered cartilage can be modulated by the conditions and duration of in vitro cultivation, using three different environments: static flasks, mixed flasks, and rotating vessels. After 4-6 weeks, static culture yielded small and fragile constructs, while turbulent flow in mixed flasks induced the formation of an outer fibrous capsule; both environments resulted in constructs with poor mechanical properties. The constructs that were cultured freely suspended in a dynamic laminar flow field in rotating vessels had the highest fractions of glycosaminoglycans and collagen (respectively 75% and 39% of levels measured in native cartilage), and the best mechanical properties (equilibrium modulus, hydraulic permeability, dynamic stiffness, and streaming potential were all about 20% of values measured in native cartilage). Chondrocytes in cartilaginous constructs remained metabolically active and phenotypically stable over prolonged cultivation in rotating bioreactors. The wet weight fraction of glycosaminoglycans and equilibrium modulus of 7 month constructs reached or exceeded the corresponding values measured from freshly explanted native cartilage. Taken together, these findings suggest that functional equivalents of native cartilage can be engineered by optimizing the hydrodynamic conditions in tissue culture bioreactors and the duration of tissue cultivation.",
publisher = "IOS Press, Amsterdam",
journal = "Biorheology",
title = "Modulation of the mechanical properties of tissue engineered cartilage",
pages = "147-141",
number = "1-2",
volume = "37",
url = "https://hdl.handle.net/21.15107/rcub_technorep_298"
}

Martin, I., Obradović, B., Treppo, S., Grodzinsky, A., Langer, R., Freed, L.,& Vunjak-Novaković, G.. (2000). Modulation of the mechanical properties of tissue engineered cartilage. in Biorheology
IOS Press, Amsterdam., 37(1-2), 141-147.
https://hdl.handle.net/21.15107/rcub_technorep_298

Martin I, Obradović B, Treppo S, Grodzinsky A, Langer R, Freed L, Vunjak-Novaković G. Modulation of the mechanical properties of tissue engineered cartilage. in Biorheology. 2000;37(1-2):141-147.
https://hdl.handle.net/21.15107/rcub_technorep_298 .

Martin, Ivan, Obradović, Bojana, Treppo, S, Grodzinsky, AJ, Langer, R, Freed, LE, Vunjak-Novaković, Gordana, "Modulation of the mechanical properties of tissue engineered cartilage" in Biorheology, 37, no. 1-2 (2000):141-147,
https://hdl.handle.net/21.15107/rcub_technorep_298 .

TY  - JOUR
AU  - Ameer, GA
AU  - Grovender, EA
AU  - Obradović, Bojana
AU  - Cooney, CL
AU  - Langer, R
PY  - 1999
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/248
AB  - Heparin is an anticoagulant used in extracorporeal procedures such as hemodialysis and open heart surgery. Unfortunately: heparin may induce potentially fatal complications in patients at high risk of bleeding. The use of art immobilized heparinase I reactor makes heparin therapy safer; but the design of a safe and efficient reactor for medical use had been a significant problem. A novel reactor, based on simultaneous separation-reaction and Taylor-Couette flow, was designed and successfully tested in vitro with human blood and ex vivo in sleep. The objective of this study was to understand the flow dynamics in the reactor in order to predict and optimize heparin neutralization. Residence-time distribution studies were performed and a mathematical model was developed The model was able to predict experimental conversions within a mean relative error of 5.5%. Bypass flow through the reactive section was also predicted.
PB  - Amer Inst Chemical Engineers, New York
T2  - AICHE Journal
T1  - RTD analysis of a novel Taylor-Couette flow device for blood detoxification
EP  - 638
IS  - 3
SP  - 633
VL  - 45
DO  - 10.1002/aic.690450320
ER  - 

@article{
author = "Ameer, GA and Grovender, EA and Obradović, Bojana and Cooney, CL and Langer, R",
year = "1999",
abstract = "Heparin is an anticoagulant used in extracorporeal procedures such as hemodialysis and open heart surgery. Unfortunately: heparin may induce potentially fatal complications in patients at high risk of bleeding. The use of art immobilized heparinase I reactor makes heparin therapy safer; but the design of a safe and efficient reactor for medical use had been a significant problem. A novel reactor, based on simultaneous separation-reaction and Taylor-Couette flow, was designed and successfully tested in vitro with human blood and ex vivo in sleep. The objective of this study was to understand the flow dynamics in the reactor in order to predict and optimize heparin neutralization. Residence-time distribution studies were performed and a mathematical model was developed The model was able to predict experimental conversions within a mean relative error of 5.5%. Bypass flow through the reactive section was also predicted.",
publisher = "Amer Inst Chemical Engineers, New York",
journal = "AICHE Journal",
title = "RTD analysis of a novel Taylor-Couette flow device for blood detoxification",
pages = "638-633",
number = "3",
volume = "45",
doi = "10.1002/aic.690450320"
}

Ameer, G., Grovender, E., Obradović, B., Cooney, C.,& Langer, R.. (1999). RTD analysis of a novel Taylor-Couette flow device for blood detoxification. in AICHE Journal
Amer Inst Chemical Engineers, New York., 45(3), 633-638.
https://doi.org/10.1002/aic.690450320

Ameer G, Grovender E, Obradović B, Cooney C, Langer R. RTD analysis of a novel Taylor-Couette flow device for blood detoxification. in AICHE Journal. 1999;45(3):633-638.
doi:10.1002/aic.690450320 .

Ameer, GA, Grovender, EA, Obradović, Bojana, Cooney, CL, Langer, R, "RTD analysis of a novel Taylor-Couette flow device for blood detoxification" in AICHE Journal, 45, no. 3 (1999):633-638,
https://doi.org/10.1002/aic.690450320 . .

TY  - JOUR
AU  - Vunjak-Novaković, Gordana
AU  - Martin, Ivan
AU  - Obradović, Bojana
AU  - Treppo, S
AU  - Grodzinsky, AJ
AU  - Langer, R
AU  - Freed, LE
PY  - 1999
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/243
AB  - Cartilaginous constructs have been grown in vitro with use of isolated cells, biodegradable polymer scaffolds, and bioreactors. In the present work, the relationships between the composition and mechanical properties of engineered cartilage constructs were studied by culturing bovine calf articular chondrocytes on fibrous polyglycolic acid scaffolds (5 mm in diameter, 2-mm thick, and 97% porous) in three different environments: static flasks, mixed flasks, and rotating vessels. After 6 weeks of cultivation, the composition, morphology, and mechanical function of the constructs in radially confined static and dynamic compression all depended on the conditions of in vitro cultivation. Static culture yielded small and fragile constructs, while turbulent flow in mixed flasks yielded constructs with fibrous outer capsules; both environments resulted in constructs with poor mechanical properties. The constructs that were cultured freely suspended in a dynamic laminar flow field in rotating vessels were the largest, contained continuous cartilage-like extracellular matrices with the highest fractions of glycosaminoglycan and collagen, and had the best mechanical properties. The equilibrium modulus, hydraulic permeability, dynamic stiffness, and streaming potential correlated with the wet-weight fractions of glycosaminoglycan, collagen, and water. These findings suggest that the hydrodynamic conditions in tissue-culture bioreactors can modulate the composition, morphology, mechanical properties, and electromechanical function of engineered cartilage.
PB  - Wiley, Hoboken
T2  - Journal of Orthopaedic Research
T1  - Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage
EP  - 138
IS  - 1
SP  - 130
VL  - 17
DO  - 10.1002/jor.1100170119
ER  - 

@article{
author = "Vunjak-Novaković, Gordana and Martin, Ivan and Obradović, Bojana and Treppo, S and Grodzinsky, AJ and Langer, R and Freed, LE",
year = "1999",
abstract = "Cartilaginous constructs have been grown in vitro with use of isolated cells, biodegradable polymer scaffolds, and bioreactors. In the present work, the relationships between the composition and mechanical properties of engineered cartilage constructs were studied by culturing bovine calf articular chondrocytes on fibrous polyglycolic acid scaffolds (5 mm in diameter, 2-mm thick, and 97% porous) in three different environments: static flasks, mixed flasks, and rotating vessels. After 6 weeks of cultivation, the composition, morphology, and mechanical function of the constructs in radially confined static and dynamic compression all depended on the conditions of in vitro cultivation. Static culture yielded small and fragile constructs, while turbulent flow in mixed flasks yielded constructs with fibrous outer capsules; both environments resulted in constructs with poor mechanical properties. The constructs that were cultured freely suspended in a dynamic laminar flow field in rotating vessels were the largest, contained continuous cartilage-like extracellular matrices with the highest fractions of glycosaminoglycan and collagen, and had the best mechanical properties. The equilibrium modulus, hydraulic permeability, dynamic stiffness, and streaming potential correlated with the wet-weight fractions of glycosaminoglycan, collagen, and water. These findings suggest that the hydrodynamic conditions in tissue-culture bioreactors can modulate the composition, morphology, mechanical properties, and electromechanical function of engineered cartilage.",
publisher = "Wiley, Hoboken",
journal = "Journal of Orthopaedic Research",
title = "Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage",
pages = "138-130",
number = "1",
volume = "17",
doi = "10.1002/jor.1100170119"
}

Vunjak-Novaković, G., Martin, I., Obradović, B., Treppo, S., Grodzinsky, A., Langer, R.,& Freed, L.. (1999). Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage. in Journal of Orthopaedic Research
Wiley, Hoboken., 17(1), 130-138.
https://doi.org/10.1002/jor.1100170119

Vunjak-Novaković G, Martin I, Obradović B, Treppo S, Grodzinsky A, Langer R, Freed L. Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage. in Journal of Orthopaedic Research. 1999;17(1):130-138.
doi:10.1002/jor.1100170119 .

Vunjak-Novaković, Gordana, Martin, Ivan, Obradović, Bojana, Treppo, S, Grodzinsky, AJ, Langer, R, Freed, LE, "Bioreactor cultivation conditions modulate the composition and mechanical properties of tissue-engineered cartilage" in Journal of Orthopaedic Research, 17, no. 1 (1999):130-138,
https://doi.org/10.1002/jor.1100170119 . .

TY  - JOUR
AU  - Vunjak-Novaković, Gordana
AU  - Obradović, Bojana
AU  - Martin, Ivan
AU  - Bursac, PM
AU  - Langer, R
AU  - Freed, LE
PY  - 1998
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/193
AB  - Cell seeding of three-dimensional polymer scaffolds is the first step of the cultivation of engineered tissues in bioreactors. Seeding requirements of large scaffolds to make implants for potential clinical use include: (a) high yield, to maximize the utilization of donor cells, (b) high kinetic rate, to minimize the time in suspension for anchorage-dependent and shear-sensitive cells, and
PB  - Wiley, Hoboken
T2  - Biotechnology Progress
T1  - Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering
EP  - 202
IS  - 2
SP  - 193
VL  - 14
DO  - 10.1021/bp970120j
ER  - 

@article{
author = "Vunjak-Novaković, Gordana and Obradović, Bojana and Martin, Ivan and Bursac, PM and Langer, R and Freed, LE",
year = "1998",
abstract = "Cell seeding of three-dimensional polymer scaffolds is the first step of the cultivation of engineered tissues in bioreactors. Seeding requirements of large scaffolds to make implants for potential clinical use include: (a) high yield, to maximize the utilization of donor cells, (b) high kinetic rate, to minimize the time in suspension for anchorage-dependent and shear-sensitive cells, and",
publisher = "Wiley, Hoboken",
journal = "Biotechnology Progress",
title = "Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering",
pages = "202-193",
number = "2",
volume = "14",
doi = "10.1021/bp970120j"
}

Vunjak-Novaković, G., Obradović, B., Martin, I., Bursac, P., Langer, R.,& Freed, L.. (1998). Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering. in Biotechnology Progress
Wiley, Hoboken., 14(2), 193-202.
https://doi.org/10.1021/bp970120j

Vunjak-Novaković G, Obradović B, Martin I, Bursac P, Langer R, Freed L. Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering. in Biotechnology Progress. 1998;14(2):193-202.
doi:10.1021/bp970120j .

Vunjak-Novaković, Gordana, Obradović, Bojana, Martin, Ivan, Bursac, PM, Langer, R, Freed, LE, "Dynamic cell seeding of polymer scaffolds for cartilage tissue engineering" in Biotechnology Progress, 14, no. 2 (1998):193-202,
https://doi.org/10.1021/bp970120j . .