Effects of mixing intensity on tissue-engineered cartilage

Gooch, Keith J.; Kwon, Jae Hyun; Blunk, Torsten; Langer, Robert; Freed, Lisa E.; Vunjak-Novakovic, Gordana

doi:10.1002/1097-0290(20000220)72:4<402::aid-bit1002>3.0.co;2-q

Cited by 144 publications

(94 citation statements)

References 24 publications

(29 reference statements)

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“…From studies using a tracer dye it was concluded that spinner flasks and RWV bioreactors closely approximated perfectly mixed conditions (55). However, the measured oxygen level in the medium ranged from 65% to 87% of the equilibrium with the incubator atmosphere in RWV and spinner flask culture (11,27). In addition, depending on the local flow environment concentrations around the construct may be lower due to cellular uptake (12).…”

Section: Discussionmentioning

confidence: 99%

“…Static culture tends to produce constructs with an inhomogeneous matrix distribution, with enhanced deposition in the periphery. Mixing enhances mass transfer, increasing both the amount of GAG synthesized and the amount of GAG released to the medium (11). Constructs cultured in RWVs displayed uniform cartilage formation and contained the highest amounts of ECM components (3).…”

Section: Introductionmentioning

confidence: 99%

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Computational Study of Culture Conditions and Nutrient Supply in Cartilage Tissue Engineering

Sengers

Donkelaar

Oomens

et al. 2008

Biotechnol Progress

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Different culture conditions for cartilage tissue engineering were evaluated with respect to the supply of oxygen and glucose and the accumulation of lactate. A computational approach was adopted in which the culture configurations were modeled as a batch process and transport was considered within constructs seeded at high cell concentrations and of clinically relevant dimensions. To assess the extent to which mass transfer can be influenced theoretically, extreme cases were distinguished in which the culture medium surrounding the construct was assumed either completely static or well mixed and fully oxygenated. It can be concluded that severe oxygen depletion and lactate accumulation can occur within constructs for cartilage tissue engineering. However, the results also indicate that transport restrictions are not insurmountable, providing that the medium is well homogenized and oxygenated and the construct's surfaces are sufficiently exposed to the medium. The large variation in uptake rates of chondrocytes indicates that for any specific application the quantification of cellular utilization rates, depending on the cell source and culture conditions, is an essential starting point for optimizing culture protocols.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Computational Study of Culture Conditions and Nutrient Supply in Cartilage Tissue Engineering

Sengers

Donkelaar

Oomens

et al. 2008

Biotechnol Progress

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“…38 Stirred vessels have been used for dynamic seeding of scaffolds resulting from increased collisions. 39 Low-gravity devices have yielded better mass transfer obtained by achieving Reynolds numbers more conducive to a minimal boundary layer. 40 Axial loading devices have been shown to increase the rate of growth for tissue such as central nervous axons.…”

Section: Previous Bioreactor Designsmentioning

confidence: 99%

Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs

Paten

Zareian

Saeidi

et al. 2011

Tissue Engineering Part C: Methods

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Currently available bioreactor systems used by tissue engineers permit either direct, high-magnification observation of cell behavior or application of mechanical loads to growing tissue constructs, but not both simultaneously. Further, in most loading bioreactors, the volume of the dead space is not minimized to reduce the cost associated with perfusion media, exogenous stimulatory/inhibitory agents, proteases, and label. We have designed, developed, and tested a bioreactor that simultaneously satisfies the combined requirements of providing (i) controlled tensile mechanical stimulation, (ii) direct high-magnification imaging capability, and (iii) low dead-space volume. This novel mechanostimulatory (uniaxial tensile loading) bioreactor operates on an inverted microscope and permits continuous optical access (up to 600 · ) to a loaded, growing construct for extended periods of time (weeks). The reactor employs an adjustable reaction chamber in which the dead space can be reduced to < 2 mL. The device has been used to cultivate our human primary corneal fibroblastderived, tissue-engineered system for up to 14 days. Using the instrument we have successfully recorded (i) the process of fibroblasts populating, growing to confluence, and stratifying on different substrates; (ii) recorded complex and organized cell sheet motions; and (iii) recorded the behavior of a subpopulation of what appear to be degradative/catabolic cells within our fibroblast culture. The device is capable of providing detailed, long-term, dynamic images of mechanically stimulated cell/matrix interaction that have not been observed previously.

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“…The ideal bioreactor for tissue engineering would allow for efficient, homogeneous mixing with controlled mechanical stimuli and a sufficient nutrient and oxygen supply without mass transport and diffusion limitations in the interior of the scaffold (11,(22)(23)(24)(25). Furthermore, the bioreactor should provide control of environmental conditions such as oxygen, pH, temperature, or the medium flow rate (7).…”

Section: Introductionmentioning

confidence: 99%

Design and Characterization of a Rotating Bed System Bioreactor for Tissue Engineering Applications

Anton¹,

Suck²,

Diederichs³

et al. 2008

Biotechnol. Prog.

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The main challenge in the development of bioreactors for tissue engineering is the delivery of a sufficient nutrient and oxygen supply for cell growth in a 3D environment. Thus, a new rotating bed system bioreactor for tissue engineering applications was developed. The system consists of a culture vessel as well as an integrated rotating bed of special porous ceramic discs and a process control unit connected with the reactor to ensure optimal culturing conditions. The aim of the project was the design and construction of a fully equipped rotating bed reactor, and in particular, the characterization and optimization of the system with regard to technical parameters such as mixing time and pH-control to guarantee optimal conditions for cell growth and differentiation. Furthermore, the applicability of the developed system was demonstrated by cultivation of osteoblast precursor cells. The porous structure of the ceramic discs and the external medium circulation loop provide an optimal environment for tissue generation in long-term cultivations. Mass transfer limitations were minimized by the slow rotation, which also provides the cells with sufficient nutrients and oxygen through alternate contact to air and medium. An osteoblast precursor cell line was successfully cultivated in this bioreactor for 28 days.

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Effects of mixing intensity on tissue-engineered cartilage

Cited by 144 publications

References 24 publications

Computational Study of Culture Conditions and Nutrient Supply in Cartilage Tissue Engineering

Computational Study of Culture Conditions and Nutrient Supply in Cartilage Tissue Engineering

Design and Performance of an Optically Accessible, Low-Volume, Mechanobioreactor for Long-Term Study of Living Constructs

Design and Characterization of a Rotating Bed System Bioreactor for Tissue Engineering Applications

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