TY  - JOUR
AU  - Vunjak-Novaković, Gordana
AU  - Obradović, Bojana
AU  - Martin, Ivan
AU  - Freed, LE
PY  - 2002
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/445
AB  - Functional tissue engineering of cartilage involves the use of bioreactors designed to provide a controlled in vitro environment that embodies some of the biochemical and physical signals known to regulate chondrogenesis. Hydrodynamic conditions can affect in vitro tissue formation in at least two ways: by direct effects of hydrodynamic forces on cell morphology and function, and by indirect flow-induced changes in mass transfer of nutrients and metabolites. In the present work, we discuss the effects of three different in vitro environments: static flasks (tissues fixed in place, static medium), mixed flasks (tissues fixed in place, unidirectional turbulent flow) and rotating bioreactors (tissues dynamically suspended in laminar flow) on engineered cartilage constructs and native cartilage explants. As compared to static and mixed flasks, dynamic laminar flow in rotating bioreactors resulted in the most rapid tissue growth and the highest final fractions of glycosaminoglycans and total collagen in both tissues. Mechanical properties (equilibrium modulus, dynamic stiffness, hydraulic permeability) of engineered constructs and explanted cartilage correlated with the wet weight fractions of glycosaminoglycans and collagen. Current research needs in the area of cartilage tissue engineering include the utilization of additional physiologically relevant regulatory signals, and the development of predictive mathematical models that enable optimization of the conditions and duration of tissue culture.
PB  - IOS Press, Amsterdam
T2  - Biorheology
T1  - Bioreactor studies of native and tissue engineered cartilage
EP  - 268
IS  - 1-2
SP  - 259
VL  - 39
UR  - https://hdl.handle.net/21.15107/rcub_technorep_445
ER  - 

@article{
author = "Vunjak-Novaković, Gordana and Obradović, Bojana and Martin, Ivan and Freed, LE",
year = "2002",
abstract = "Functional tissue engineering of cartilage involves the use of bioreactors designed to provide a controlled in vitro environment that embodies some of the biochemical and physical signals known to regulate chondrogenesis. Hydrodynamic conditions can affect in vitro tissue formation in at least two ways: by direct effects of hydrodynamic forces on cell morphology and function, and by indirect flow-induced changes in mass transfer of nutrients and metabolites. In the present work, we discuss the effects of three different in vitro environments: static flasks (tissues fixed in place, static medium), mixed flasks (tissues fixed in place, unidirectional turbulent flow) and rotating bioreactors (tissues dynamically suspended in laminar flow) on engineered cartilage constructs and native cartilage explants. As compared to static and mixed flasks, dynamic laminar flow in rotating bioreactors resulted in the most rapid tissue growth and the highest final fractions of glycosaminoglycans and total collagen in both tissues. Mechanical properties (equilibrium modulus, dynamic stiffness, hydraulic permeability) of engineered constructs and explanted cartilage correlated with the wet weight fractions of glycosaminoglycans and collagen. Current research needs in the area of cartilage tissue engineering include the utilization of additional physiologically relevant regulatory signals, and the development of predictive mathematical models that enable optimization of the conditions and duration of tissue culture.",
publisher = "IOS Press, Amsterdam",
journal = "Biorheology",
title = "Bioreactor studies of native and tissue engineered cartilage",
pages = "268-259",
number = "1-2",
volume = "39",
url = "https://hdl.handle.net/21.15107/rcub_technorep_445"
}

Vunjak-Novaković, G., Obradović, B., Martin, I.,& Freed, L.. (2002). Bioreactor studies of native and tissue engineered cartilage. in Biorheology
IOS Press, Amsterdam., 39(1-2), 259-268.
https://hdl.handle.net/21.15107/rcub_technorep_445

Vunjak-Novaković G, Obradović B, Martin I, Freed L. Bioreactor studies of native and tissue engineered cartilage. in Biorheology. 2002;39(1-2):259-268.
https://hdl.handle.net/21.15107/rcub_technorep_445 .

Vunjak-Novaković, Gordana, Obradović, Bojana, Martin, Ivan, Freed, LE, "Bioreactor studies of native and tissue engineered cartilage" in Biorheology, 39, no. 1-2 (2002):259-268,
https://hdl.handle.net/21.15107/rcub_technorep_445 .

TY  - JOUR
AU  - Obradović, Bojana
AU  - Martin, Ivan
AU  - Padera, RF
AU  - Treppo, S
AU  - Freed, LE
AU  - Vunjak-Novaković, Gordana
PY  - 2001
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/371
AB  - The structure and function of cartilaginous constructs, engineered in vitro using bovine articular chondrocytes, biodegradable scaffolds and bioreactors, can be modulated by the conditions and duration of tissue cultivation. We hypothesized that the integrative properties of engineered cartilage depend on developmental stage of the construct and the extracellular matrix content of adjacent cartilage, and that some aspects of integration can be studied under controlled in vitro conditions. Disc-shaped constructs (cultured for 5 +/- 1 days or 5 +/- 1 weeks) or explants (untreated or trypsin treated cartilage) were sutured into ring-shaped explants (untreated or trypsin treated cartilage) to form composites that were cultured for an additional 1-8 weeks in bioreactors and evaluated biochemically, histologically and mechanically (compressive stiffness of the central disk, adhesive strength of the integration interface). Immature constructs had poorer mechanical properties but integrated better than either more mature constructs or cartilage explants. Integration of immature constructs involved cell proliferation and the progressive formation of cartilaginous tissue, in contrast to the integration of more mature constructs or native cartilage which involved only the secretion of extracellular matrix components. Integration patterns correlated with the adhesive strength of the disc-ring interface, which was markedly higher for immature constructs than for either more mature constructs or cartilage explants. Trypsin treatment of the adjacent cartilage further enhanced the integration of immature constructs.
PB  - Elsevier Sci Ltd, Oxford
T2  - Journal of Orthopaedic Research
T1  - Integration of engineered cartilage
EP  - 1097
IS  - 6
SP  - 1089
VL  - 19
DO  - 10.1016/S0736-0266(01)00030-4
ER  - 

@article{
author = "Obradović, Bojana and Martin, Ivan and Padera, RF and Treppo, S and Freed, LE and Vunjak-Novaković, Gordana",
year = "2001",
abstract = "The structure and function of cartilaginous constructs, engineered in vitro using bovine articular chondrocytes, biodegradable scaffolds and bioreactors, can be modulated by the conditions and duration of tissue cultivation. We hypothesized that the integrative properties of engineered cartilage depend on developmental stage of the construct and the extracellular matrix content of adjacent cartilage, and that some aspects of integration can be studied under controlled in vitro conditions. Disc-shaped constructs (cultured for 5 +/- 1 days or 5 +/- 1 weeks) or explants (untreated or trypsin treated cartilage) were sutured into ring-shaped explants (untreated or trypsin treated cartilage) to form composites that were cultured for an additional 1-8 weeks in bioreactors and evaluated biochemically, histologically and mechanically (compressive stiffness of the central disk, adhesive strength of the integration interface). Immature constructs had poorer mechanical properties but integrated better than either more mature constructs or cartilage explants. Integration of immature constructs involved cell proliferation and the progressive formation of cartilaginous tissue, in contrast to the integration of more mature constructs or native cartilage which involved only the secretion of extracellular matrix components. Integration patterns correlated with the adhesive strength of the disc-ring interface, which was markedly higher for immature constructs than for either more mature constructs or cartilage explants. Trypsin treatment of the adjacent cartilage further enhanced the integration of immature constructs.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Journal of Orthopaedic Research",
title = "Integration of engineered cartilage",
pages = "1097-1089",
number = "6",
volume = "19",
doi = "10.1016/S0736-0266(01)00030-4"
}

Obradović, B., Martin, I., Padera, R., Treppo, S., Freed, L.,& Vunjak-Novaković, G.. (2001). Integration of engineered cartilage. in Journal of Orthopaedic Research
Elsevier Sci Ltd, Oxford., 19(6), 1089-1097.
https://doi.org/10.1016/S0736-0266(01)00030-4

Obradović B, Martin I, Padera R, Treppo S, Freed L, Vunjak-Novaković G. Integration of engineered cartilage. in Journal of Orthopaedic Research. 2001;19(6):1089-1097.
doi:10.1016/S0736-0266(01)00030-4 .

Obradović, Bojana, Martin, Ivan, Padera, RF, Treppo, S, Freed, LE, Vunjak-Novaković, Gordana, "Integration of engineered cartilage" in Journal of Orthopaedic Research, 19, no. 6 (2001):1089-1097,
https://doi.org/10.1016/S0736-0266(01)00030-4 . .

TY  - JOUR
AU  - Obradović, Bojana
AU  - Meldon, JH
AU  - Freed, LE
AU  - Vunjak-Novaković, Gordana
PY  - 2000
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/302
AB  - Functional cartilaginous constructs for scientific research and eventual tissue repair were cultivated in bioreactors starting from chondrocytes immobilized on polymeric scaffolds. The scaffolds gradually degraded as the cells regenerated tissue matrix consisting of glycosaminoglycan (GAG) and type II collagen. To facilitate data interpretation and optimize cultivation conditions, a mathematical model was developed which yields the concentrations of oxygen and GAG as functions of time and position in growing tissue. Calculated GAG concentrations were qualitatively and quantitatively consistent with profiles measured via high-resolution image processing of tissue samples cultured at two different oxygen tensions for various periods of time.
PB  - Wiley-Blackwell, Malden
T2  - AICHE Journal
T1  - Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model
EP  - 1871
IS  - 9
SP  - 1860
VL  - 46
DO  - 10.1002/aic.690460914
ER  - 

@article{
author = "Obradović, Bojana and Meldon, JH and Freed, LE and Vunjak-Novaković, Gordana",
year = "2000",
abstract = "Functional cartilaginous constructs for scientific research and eventual tissue repair were cultivated in bioreactors starting from chondrocytes immobilized on polymeric scaffolds. The scaffolds gradually degraded as the cells regenerated tissue matrix consisting of glycosaminoglycan (GAG) and type II collagen. To facilitate data interpretation and optimize cultivation conditions, a mathematical model was developed which yields the concentrations of oxygen and GAG as functions of time and position in growing tissue. Calculated GAG concentrations were qualitatively and quantitatively consistent with profiles measured via high-resolution image processing of tissue samples cultured at two different oxygen tensions for various periods of time.",
publisher = "Wiley-Blackwell, Malden",
journal = "AICHE Journal",
title = "Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model",
pages = "1871-1860",
number = "9",
volume = "46",
doi = "10.1002/aic.690460914"
}

Obradović, B., Meldon, J., Freed, L.,& Vunjak-Novaković, G.. (2000). Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model. in AICHE Journal
Wiley-Blackwell, Malden., 46(9), 1860-1871.
https://doi.org/10.1002/aic.690460914

Obradović B, Meldon J, Freed L, Vunjak-Novaković G. Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model. in AICHE Journal. 2000;46(9):1860-1871.
doi:10.1002/aic.690460914 .

Obradović, Bojana, Meldon, JH, Freed, LE, Vunjak-Novaković, Gordana, "Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model" in AICHE Journal, 46, no. 9 (2000):1860-1871,
https://doi.org/10.1002/aic.690460914 . .

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  - Martin, Ivan
AU  - Obradović, Bojana
AU  - Freed, LE
AU  - Vunjak-Novaković, Gordana
PY  - 1999
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/252
AB  - Cartilage tissue engineering can provide a valuable tool for controlled studies of tissue development. As an example, analysis of the spatial distribution of glycosaminoglycans (GAG) in sections of cartilaginous tissues engineered under different culture conditions could be used to correlate the effects of environmental factors with the structure of the regenerated tissue. In this paper we describe a computer-based technique for quantitative analysis of safranin-O stained histological sections, using low magnification light microscopy images. We identified a parameter to quantify the intensity of red color in the sections, which in turn was proportional to the biochemically determined wet weight fraction of GAG in corresponding tissue samples, and to describe the spatial distribution of GAG as a function of depth from. the section edge. A broken line regression model was then used to determine the thickness of an external region, with lower GAG fractions, and the spatial rate of change in GAG content. The method was applied to the quantitatation of GAG distribution in samples of natural and engineered cartilage, cultured for 6 weeks in three different vessels: static flasks, mixed flasks, and rotating bioreactors.
PB  - Amer Inst Physics, Woodbury
T2  - Annals of Biomedical Engineering
T1  - Method for quantitative analysis of glycosaminoglycan distribution in cultured natural and engineered cartilage
EP  - 662
IS  - 5
SP  - 656
VL  - 27
DO  - 10.1114/1.205
ER  - 

@article{
author = "Martin, Ivan and Obradović, Bojana and Freed, LE and Vunjak-Novaković, Gordana",
year = "1999",
abstract = "Cartilage tissue engineering can provide a valuable tool for controlled studies of tissue development. As an example, analysis of the spatial distribution of glycosaminoglycans (GAG) in sections of cartilaginous tissues engineered under different culture conditions could be used to correlate the effects of environmental factors with the structure of the regenerated tissue. In this paper we describe a computer-based technique for quantitative analysis of safranin-O stained histological sections, using low magnification light microscopy images. We identified a parameter to quantify the intensity of red color in the sections, which in turn was proportional to the biochemically determined wet weight fraction of GAG in corresponding tissue samples, and to describe the spatial distribution of GAG as a function of depth from. the section edge. A broken line regression model was then used to determine the thickness of an external region, with lower GAG fractions, and the spatial rate of change in GAG content. The method was applied to the quantitatation of GAG distribution in samples of natural and engineered cartilage, cultured for 6 weeks in three different vessels: static flasks, mixed flasks, and rotating bioreactors.",
publisher = "Amer Inst Physics, Woodbury",
journal = "Annals of Biomedical Engineering",
title = "Method for quantitative analysis of glycosaminoglycan distribution in cultured natural and engineered cartilage",
pages = "662-656",
number = "5",
volume = "27",
doi = "10.1114/1.205"
}

Martin, I., Obradović, B., Freed, L.,& Vunjak-Novaković, G.. (1999). Method for quantitative analysis of glycosaminoglycan distribution in cultured natural and engineered cartilage. in Annals of Biomedical Engineering
Amer Inst Physics, Woodbury., 27(5), 656-662.
https://doi.org/10.1114/1.205

Martin I, Obradović B, Freed L, Vunjak-Novaković G. Method for quantitative analysis of glycosaminoglycan distribution in cultured natural and engineered cartilage. in Annals of Biomedical Engineering. 1999;27(5):656-662.
doi:10.1114/1.205 .

Martin, Ivan, Obradović, Bojana, Freed, LE, Vunjak-Novaković, Gordana, "Method for quantitative analysis of glycosaminoglycan distribution in cultured natural and engineered cartilage" in Annals of Biomedical Engineering, 27, no. 5 (1999):656-662,
https://doi.org/10.1114/1.205 . .

TY  - JOUR
AU  - Obradović, Bojana
AU  - Carrier, RL
AU  - Vunjak-Novaković, Gordana
AU  - Freed, LE
PY  - 1999
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/249
AB  - Tissue engineered cartilage can be grown in vitro if the necessary physical and biochemical factors are present in the tissue culture environment. Cell metabolism and tissue composition were studied for engineered cartilage cultured for 5 weeks using bovine articular chondrocytes, polymer scaffolds (5 mm diameter x 2 mm thick fibrous discs), and rotating bioreactors. Medium pH and concentrations of oxygen, carbon dioxide, glucose, lactate, ammonia, and glycosoaminoglycan (GAG) were varied by altering the exchange rates of gas and medium in the bioreactors. Cell-polymer constructs were assessed with respect to histomorphology, biochemical composition and metabolic activity. Low oxygen tension (similar to 40 mmHg) and low pH (similar to 6.7) were associated with anaerobic cell metabolism (yield of lactate on glucose, Y-L/G, of 2.2 mol/mol) while higher oxygen tension (similar to 80 mmHg) and higher pH (similar to 7.0) were associated with more aerobic cell metabolism (Y-L/G of 1.65-1.79 mol/mol). Under conditions of infrequent medium replacement (50% once per week), cells utilized more economical pathways such that glucose consumption and lactate production both decreased, cell metabolism remained relatively aerobic (Y-L/G of 1.67 mol/mol) and the resulting constructs were cartilaginous. More aerobic conditions generally resulted in larger constructs containing higher amounts of cartilaginous tissue components, while anaerobic conditions suppressed chondrogenesis in 3D tissue constructs.
PB  - John Wiley & Sons Inc, New York
T2  - Biotechnology and Bioengineering
T1  - Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage
EP  - 205
IS  - 2
SP  - 197
VL  - 63
DO  - 10.1002/(SICI)1097-0290(19990420)63:2197::AID-BIT83.0.CO;2-2
ER  - 

@article{
author = "Obradović, Bojana and Carrier, RL and Vunjak-Novaković, Gordana and Freed, LE",
year = "1999",
abstract = "Tissue engineered cartilage can be grown in vitro if the necessary physical and biochemical factors are present in the tissue culture environment. Cell metabolism and tissue composition were studied for engineered cartilage cultured for 5 weeks using bovine articular chondrocytes, polymer scaffolds (5 mm diameter x 2 mm thick fibrous discs), and rotating bioreactors. Medium pH and concentrations of oxygen, carbon dioxide, glucose, lactate, ammonia, and glycosoaminoglycan (GAG) were varied by altering the exchange rates of gas and medium in the bioreactors. Cell-polymer constructs were assessed with respect to histomorphology, biochemical composition and metabolic activity. Low oxygen tension (similar to 40 mmHg) and low pH (similar to 6.7) were associated with anaerobic cell metabolism (yield of lactate on glucose, Y-L/G, of 2.2 mol/mol) while higher oxygen tension (similar to 80 mmHg) and higher pH (similar to 7.0) were associated with more aerobic cell metabolism (Y-L/G of 1.65-1.79 mol/mol). Under conditions of infrequent medium replacement (50% once per week), cells utilized more economical pathways such that glucose consumption and lactate production both decreased, cell metabolism remained relatively aerobic (Y-L/G of 1.67 mol/mol) and the resulting constructs were cartilaginous. More aerobic conditions generally resulted in larger constructs containing higher amounts of cartilaginous tissue components, while anaerobic conditions suppressed chondrogenesis in 3D tissue constructs.",
publisher = "John Wiley & Sons Inc, New York",
journal = "Biotechnology and Bioengineering",
title = "Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage",
pages = "205-197",
number = "2",
volume = "63",
doi = "10.1002/(SICI)1097-0290(19990420)63:2197::AID-BIT83.0.CO;2-2"
}

Obradović, B., Carrier, R., Vunjak-Novaković, G.,& Freed, L.. (1999). Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage. in Biotechnology and Bioengineering
John Wiley & Sons Inc, New York., 63(2), 197-205.
https://doi.org/10.1002/(SICI)1097-0290(19990420)63:2197::AID-BIT83.0.CO;2-2

Obradović B, Carrier R, Vunjak-Novaković G, Freed L. Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage. in Biotechnology and Bioengineering. 1999;63(2):197-205.
doi:10.1002/(SICI)1097-0290(19990420)63:2197::AID-BIT83.0.CO;2-2 .

Obradović, Bojana, Carrier, RL, Vunjak-Novaković, Gordana, Freed, LE, "Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage" in Biotechnology and Bioengineering, 63, no. 2 (1999):197-205,
https://doi.org/10.1002/(SICI)1097-0290(19990420)63:2197::AID-BIT83.0.CO;2-2 . .

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 . .