Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model

Obradović, Bojana; Meldon, Jerry H.; Freed, Lisa E.; Vunjak‐Novakovic, Gordana

doi:10.1002/aic.690460914

Cited by 205 publications

(226 citation statements)

References 33 publications

Supporting

Mentioning

206

Contrasting

Unclassified

Order By: Relevance

“…A model aiming at predicting the temporal development of the mechanical properties more precisely should include the functional interactions between the separate PG and collagen components and should take into account the time course of the synthesis of specific matrix components, which is affected by factors like mechanical stimulation, growth factors, the amount of matrix present, nutrient availability and cell proliferation. 5,37,40,43,60 For example, in contrast to the constant matrix synthesis rate assumed here, it has been demonstrated in several studies that GAG synthesis decreased as a function of time, 5,37 while collagen production can also increase in later stages of culture. 37 To provide a clear comparison between the different matrix distribution cases only the initial, linear elastic, stiffness and undeformed permeability were compared.…”

Section: Discussioncontrasting

confidence: 64%

“…10,50,53 In the course of time the construct's collagen and proteoglycan content can approach a steady state, 16 resulting from a balance between synthesis, incorporation and degradation and/or product inhibited synthesis. 23,43,62 The relation between the content of extracellular matrix constituents and biomechanical function has been investigated in various studies. For mature natural cartilage the aggregate modulus has been correlated to GAG content primarily 12,41,58 and to both GAG and collagen density.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Local Matrix Distribution and the Functional Development of Tissue Engineered Cartilage, a Finite Element Study

et al. 2004

View full text Add to dashboard Cite

Abstract-Assessment of the functionality of tissue engineered cartilage constructs is hampered by the lack of correlation between global measurements of extra cellular matrix constituents and the global mechanical properties. Based on patterns of matrix deposition around individual cells, it has been hypothesized previously, that mechanical functionality arises when contact occurs between zones of matrix associated with individual cells. The objective of this study is to determine whether the local distribution of newly synthesized extracellular matrix components contributes to the evolution of the mechanical properties of tissue engineered cartilage constructs. A computational homogenization approach was adopted, based on the concept of a periodic representative volume element. Local transport and immobilization of newly synthesized matrix components were described. Mechanical properties were taken dependent on the local matrix concentration and subsequently the global aggregate modulus and hydraulic permeability were derived. The transport parameters were varied to assess the effect of the evolving matrix distribution during culture. The results indicate that the overall stiffness and permeability are to a large extent insensitive to differences in local matrix distribution. This emphasizes the need for caution in the visual interpretation of tissue functionality from histology and underlines the importance of complementary measurements of the matrix's intrinsic molecular organization.

show abstract

Section: Discussioncontrasting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

The Local Matrix Distribution and the Functional Development of Tissue Engineered Cartilage, a Finite Element Study

et al. 2004

View full text Add to dashboard Cite

show abstract

“…This raised the question: how do equine articular chondrocytes achieve to deal their energy needs and how much oxygen do they consume in presence of different glucose concentrations in the medium. Many authors reported data on O 2 consumption by chondrocytes (Haselgrove et al, 1993;Nehring et al, 1999;Obradovic and Meldon, 2000;Malda et al, 2004) but their approaches were generally tissue engineering for cartilage repair and thus cell multiplication with most often cartilage dedifferentiation. They often used immature cartilage.…”

Section: Introductionmentioning

confidence: 99%

Oxygen consumption of equine articular chondrocytes: Influence of applied oxygen tension and glucose concentration during culture

Schneider¹,

Mouithys-Mickalad²,

Lejeune³

et al. 2007

Cell Biology International

View full text Add to dashboard Cite

We investigated the oxygen (O 2 ) uptake of equine articular chondrocytes to assess their reactions to anoxia/reoxygenation. They were cultured under 5% or 21% gas phase O 2 and at glucose concentrations of 0, 1.0 or 4.5 g/L in the culture medium (n = 3). Afterwards, the O 2 consumption rate of the chondrocytes was monitored (oxymetry) before and after an anoxia period of 25 min. The glucose consumption and lactate release were measured at the end of the re-oxygenation period. The chondrocytes showed a minimal O 2 consumption rate, which was hardly changed by anoxia. Independently from the O 2 tension, glucose uptake by the cells was about 30% of the available culture medium glucose, thus higher for cells at 4.5 g/L glucose (n = 3). Lactate release was also independent from O 2 tension, but lower for cells at 4.5 g/L glucose (n = 3). Our observations indicated that O 2 consumption by equine chondrocytes was very low despite a functional mitochondrial respiratory chain, and nearly insensitive to anoxia/re-oxygenation. But the chondrocytes metabolism was modified by an excess of O 2 and glucose.

show abstract

“…Most nutrient or metabolite uptake rates are known to follow saturation kinetics and are modeled with MichaelisMenten (MM) kinetics (Allen and Bhatia, 2003;BenAbraham et al, 2003;Obradovic et al, 2000), and the values of the MM parameters can be measured from experiments done with static culture protocols. The mathematical expression of the specific uptake rate for species i by cell type j (R up,ij ) would thus take the form…”

Section: Model Formulationmentioning

confidence: 99%

“…Transport in perfusion bioreactors has been studied in various contexts and mathematical transport models at various levels of complexity have been developed to characterize the microenvironment for a wide variety of bioreactor designs (Botchwey et al, 2003;Galban and Locke, 1999;Ghanem and Shuler, 2000;Horner et al, 1998;Netti and Jain, 2003;Williams et al, 2002). Transport of nutrients such as oxygen has been extensively studied for various reactor geometry and cell types (Allen and Bhatia, 2003;Horner et al, 1998;Obradovic et al, 2000;Pathi et al, 2005;Roy et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Model‐based analysis and design of a microchannel reactor for tissue engineering

Mehta

Linderman

2006

Biotech & Bioengineering

View full text Add to dashboard Cite

Recently developed perfusion micro-bioreactors offer the promise of more physiologic in vitro systems for tissue engineering. Successful application of such bioreactors will require a method to characterize the bioreactor environment required to elicit desired cell function. We present a mathematical model to describe nutrient/growth factor transport and cell growth inside a microchannel bioreactor. Using the model, we first show that the nature of spatial gradients in nutrient concentration can be controlled by both design and operating conditions and are a strong function of cell uptake rates. Next, we extend our model to investigate the spatial distributions of cell-secreted soluble autocrine/paracrine growth factors in the bioreactor. We show that the convective transport associated with the continuous cell culture and possible media recirculation can significantly alter the concentration distribution of the soluble signaling molecules as compared to static culture experiments and hence needs special attention when adapting static culture protocols for the bioreactor. Further, using an unsteady state model, we find that spatial gradients in nutrient/growth factor concentrations can bring about spatial variations in the cell density distribution inside the bioreactor, which can result in lowered working volume of the bioreactor. Finally, we show that the nutrient and spatial limitations can dramatically affect the composition of a co-cultured cell population. Our results are significant for the development, design, and optimization of novel micro-channel systems for tissue engineering.

show abstract

Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model

Cited by 205 publications

References 33 publications

The Local Matrix Distribution and the Functional Development of Tissue Engineered Cartilage, a Finite Element Study

The Local Matrix Distribution and the Functional Development of Tissue Engineered Cartilage, a Finite Element Study

Oxygen consumption of equine articular chondrocytes: Influence of applied oxygen tension and glucose concentration during culture

Model‐based analysis and design of a microchannel reactor for tissue engineering

Contact Info

Product

Resources

About