Comutational Study of Oxygen and Glucose Transport in Engineered Cartilage Constructs

2011 ◽  
Vol 27 (3) ◽  
pp. 337-346 ◽  
Author(s):  
T.-H. Lin ◽  
C.-H. Lin ◽  
C. A. Chung

ABSTRACTThis paper characterizes the mass transfer and replenishment of glucose and oxygen in tissue engineered cartilage constructs by a numerical approach. Cell population growth modulated by glucose and oxygen is incorporated in the mathematic model. The distribution of synthesized type II collagen and its influence on mediating the chondrocyte growth over scaffold are also investigated. Results from simulation are compared with the experiments in literature to verify the formulation and predictions. It is found that, under static culture, the oftentimes observed phenomenon that the overall cell number densities in thick scaffolds are smaller than in thin scaffolds is mainly due to depletion of glucose rather than oxygen. Cell growth is found to be more sensitive to the change in glucose concentration for thick scaffolds, whereas to be more sensitive to the change in oxygen concentration for thin scaffolds. Results also demonstrate the modulation of chondrocyte growth by type II collagen, presenting the biphasic impact of type II collagen which promotes chondrocyte growth in the initial phase of cultivation, while inhibits cell growth in the long term. The numerical model provides a useful reference for developing cartilaginous constructs in tissue engineering.

Author(s):  
Liming Bian ◽  
Terri Ann N. Kelly ◽  
Eric G. Lima ◽  
Gerard A. Ateshian ◽  
Clark T. Hung

Proteoglycans and Type II collagen represent the two major biochemical constituents of articular cartilage. Collagen fibrils in cartilage resist the swelling pressure that arises from the fixed charges of the glycosaminoglycans (GAGs), and together they give rise to the tissue’s unique load bearing properties. As articular cartilage exhibits a poor intrinsic healing capacity, there is significant research in the development of cell-based therapies for cartilage repair. In some of our tissue engineering studies, we have observed a phenomenon where chondrocyte-seeded hydrogel constructs display cracking in their central regions after significant GAG content has been elaborated in culture. A theoretical analysis was performed to gain greater insights into the potential role that the spatial distribution of proteoglycan and collagen may play in this observed response.


Biomaterials ◽  
2010 ◽  
Vol 31 (36) ◽  
pp. 9415-9421 ◽  
Author(s):  
Ping-Jung Su ◽  
Wei-Liang Chen ◽  
Tsung-Hsien Li ◽  
Chen-Kuan Chou ◽  
Te-Hsuen Chen ◽  
...  

2004 ◽  
Vol 50 (5) ◽  
pp. 1390-1399 ◽  
Author(s):  
Robert Landewé ◽  
Piet Geusens ◽  
Maarten Boers ◽  
Désirée van der Heijde ◽  
Willem Lems ◽  
...  

2017 ◽  
Vol 46 (2) ◽  
pp. 420-430 ◽  
Author(s):  
Jana Riegger ◽  
Madeleine Zimmermann ◽  
Helga Joos ◽  
Thomas Kappe ◽  
Rolf E. Brenner

Background: Cryotherapy is routinely administered after sports injuries of synovial joints. Although positive clinical effects on periarticular swelling and pain have been described, the effects on the cell biological activities of cartilage and synovial cells remain largely unknown so far. Hypothesis: Local hypothermia alleviates synovial reactions and prevents chondrocyte death as well as cartilage destructive processes after blunt cartilage trauma. Study Design: Controlled laboratory study. Methods: Human cartilage explants were impacted by a drop-tower apparatus (0.59 J) and cultured at 24 hours or 7 days in different temperature conditions (2 hours [short term], 16 hours [medium term], or throughout [long term] at 27°C; afterwards or throughout at 37°C). Besides, isolated human fibroblast-like synoviocytes (FLS) were stimulated with traumatized cartilage conditioned medium and cultured as mentioned above up to 4 days. The effects of hypothermia were evaluated by cell viability, gene expression, type II collagen synthesis and cleavage, as well as the release of matrix metalloproteinase (MMP)–2, MMP-13, and interleukin 6 (IL-6). Results: Seven days after trauma, hypothermic treatment throughout improved cell viability (short term: 10.1% [ P = .016]; medium term: 6% [ P = .0362]; long term: 12.5% [ P = .0039]). Short-term hypothermia attenuated the expression of catabolic MMP-13 (mRNA: –2.2-fold [ P = .0119]; protein: –2-fold [ P = .0238]). Whereas type II collagen synthesis (1.7-fold [ P = .0227]) was increased after medium-term hypothermia, MMP-13 expression (mRNA: –30.8-fold [ P = .0025]; protein: –10.3-fold [ P < .0001]) and subsequent cleavage of type II collagen (–1.1-fold [ P = .0489]) were inhibited. Long-term hypothermia further suppressed MMP release (pro–MMP-2: –3-fold [ P = .0222]; active MMP-2: −5.2-fold [ P = .0183]; MMP-13: −56-fold [ P < .0001]) and type II collagen breakdown (–1.6-fold [ P = .0036]). Four days after FLS stimulation, hypothermia significantly suppressed the gene expression of matrix-destructive enzymes after medium-term (MMP-3: –4.1-fold [ P = .0211]) and long-term exposure (a disintegrin and metalloproteinase with thrombospondin motifs 4 [ADAMTS4]: –4.3-fold [ P = .0045]; MMP-3: –25.8-fold [ P = .014]; MMP-13: –122-fold [ P = .0444]) and attenuated IL-6 expression by trend. Conclusion: After blunt cartilage trauma, initial hypothermia for only 2 hours and/or 16 hours induced significant cell-protective and chondroprotective effects and promoted the anabolic activity of chondrocytes, while the expression of matrix-destructive enzymes by stimulated FLS was attenuated by prolonged hypothermia. Clinical Relevance: The findings of this preliminary ex vivo investigation indicate that optimized cryotherapy management after cartilage trauma might prevent matrix-degenerative processes associated with the pathogenesis of posttraumatic osteoarthritis.


2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Eric Tong ◽  
Grace D. O'Connell ◽  
Terri-Ann N. Kelly ◽  
Clark T. Hung

Osteoarthritis, a chronic malady characterized by joint pain and swelling, is caused by damage to articular cartilage and is perpetuated by low-grade inflammation.  Treatments for osteoarthritis do exist, but many treatments focus on coping with the disease rather than curing it.  Surgical options that replace damaged cartilage tissue with that of donor cartilage tissue or cartilage tissue from other parts of articular joints face complications especially when the tissue is not of the correct size or does not have native-like properties. A more suitable treatment option for osteoarthritis is to develop an in vitro tissue-engineered cartilage construct that can be grown using the patient’s own cells and to surgically remove the patient’s damaged cartilage and replace it with the tissue-engineered cartilage. A challenge in developing such a treatment option is producing tissue-engineered cartilage with mechanical properties akin to those of native human articular cartilage. This challenge may be overcome by maximizing the production of type II collagen by the chondrocytes in vitro. One way to maximize collagen production is through the application of chondroitinase ABC, an enzyme which temporarily suppresses proteoglycans in the cartilage matrix to create more space for type II collagen to develop. In this study, two two levels of cABC treatment were applied (“high” and “low”) to cartilage tissue constructs. The “low” cABC treated group received daily feeding of 0.075 U/mL from day 14 to 21 followed by a replacement of chondrogenic media without cABC.  The “high” cABC treated group received a single addition of 0.15 U/mL from day 14 to 16 followed by a replacement of chondrogenic media without cABC.  At the end of 42 days, the constructs were subjected to mechanical testing and biochemical analyses. These analyses showed that the high cABC treatment yielded more native-like mechanical properties when compared to the low cABC treatment and the control results.  Biochemical and histological analyses confirmed that the proteoglycan and collagen II content were higher in the low and high cABC treated groups when compared to the control. All analyses show that the most efficient application of chondroitinase ABC is through a two day duration treatment of a higher concentration (0.15 U/mL).


1990 ◽  
Vol 33 (3) ◽  
pp. 451-452
Author(s):  
B. Bannwarth ◽  
P. Gillet ◽  
P. Fener ◽  
P. Netter ◽  
A. Gaucher

1999 ◽  
Vol 58 (8) ◽  
pp. 503-509 ◽  
Author(s):  
C. J Schaefer ◽  
W D. Lawrence ◽  
P. H Wooley

Author(s):  
Chen-Yuan Chung ◽  
Mostafa Motavalli ◽  
Joseph M. Mansour

Articular cartilage is a hydrated connective tissue consisting of a relatively small number of chondrocytes surrounded by a saturated extracellular matrix comprised mainly of type-II collagen fibrils and proteoglycans. As a deformable fluid saturated material, cartilage is most often modeled using biphasic or poroelastic theories [1,2]. The ultimate goal of this work is to evaluate biomechanical properties of native and tissue engineered cartilage under combined compression and shear. The purpose of this investigation was to determine stress and deformation fields in cartilage under compression and simple shear and relate these to measured results.


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