Comparitive Phenotypic Analysis of Articular Chondrocytes Cultured within Type I or Type II Collagen Scaffolds
TISSUE ENGINEERING: Part A
Volume 14, Number 00, 2008
ª Mary Ann Liebert, Inc.
DOI: 10.1089=ten.tea.2008.0114
Anne-Marie Freyria, Ph.D.,1 Marie-Claire Ronzie` re, Ph.D.,1 Delphine Cortial, Ph.D.,1 Laurent Galois, M.D., Ph.D.,2
Daniel Hartmann, Ph.D.,3 Daniel Herbage, Ph.D.,1 and Fre´de´ ric Mallein-Gerin, Ph.D.1
Summary:
This paper investigates the differences in behavior of bovine chondrocytes in different kinds of scaffolds. To determine the best collagen-based biomaterial that could be used for cartilage repair, Freyai et. al cultured chondrocytes within scaffolds of type I or type II collagen in either sponges or gels.
The change of size of the scaffolds is a determining factor in what type of material should be used. Contraction of the scaffolds was more prevalent in the gels (40-60%) as compared to the sponges (15%), mostly due to the mechanical stability of the sponges from the crosslinking of collagen molecules. This contraction in the gels led to a formation of tissue structurally similar to cartilage that was less dense, yet stiffer than that obtained in the sponges. This could be attributed to the larger porosity of the sponges. Though the mechanical properties of both were not extensively tested, it is interesting that the gels and sponges have quite different structural components.
Also related is the expression of aggrecan, a large proteoglycan that plays a major structural role in cartilage. Aggrecan was more upregulated in the collagen gels than in the sponges. This can be contributed to aggrecan being regulated by perfusion, which is due to physical factors such as fluid flow and mass transport characteristics that are different in gels and sponges. The molecular diffusion time in tissue-engineered cartilage can result in the upregulation of aggrecan. In this case, due to the larger pore size of sponges, the expression of aggrecan was misleadingly downregulated.
Significance:
This paper points out that the contraction of collagen gels and the increase in MMP expression are negative factors for cartilage repair. Furthermore, this study suggests that type I collagen sponges are a promising material for scaffolds, due to their good maintenance of chondrocyte phonotype and minimal increase in MMP expression. Furthermore, because scaffold size in an important factor for replacement of cartilage defects, sponges are the better suited material because they are much easier to control and calibrate compared to gels.
8 comments:
The use of articular chondrocytes for the treatment of osteoarthritis and cartilage damage due to chondrocyte apoptosis is extremely important. Many millions of people are diagnosed with cartilage damage or cartilage failure and it is essential to conduct research in this area of tissue engineering. However, I am curious as to how the findings of this paper might help improve current cartilage replacement therapies such as CARTICEL and CARTICEL II. Additionally, what is MMP expression and why is an increase in MMP expression considered a negative factor for cartilage repair?
Did the authors mention why they didn't test the mechanical properties of the gels? It seems like it would be relevant for a cartilage replacement, as you'd want to imitate the actual material as much as possible. There might be significant differences when chondrocytes inhabit an existing collagen scaffold as opposed to forming their own ECM entirely.
Eric: I think this paper was simply testing if sponges would be a better scaffolds than gels in terms of what the chondrocytes express in the scaffolds. I think sponges have been a recent choice in this groups research due to the sponge's material properties. It seems likely that the gels were tested before, because collagen gels have been in use. As for the sponges, I am not exactly sure, but maybe this group wants to see if sponges are better than the gels in forming articular cartilage before testing the mechanical properties of the gels.
Rina: MMPs are matrix metalloproteinases and they are enzymes capable of degrading cartilage. So having a lower amount of it would mean that more cartilage is capable of being formed.
This paper could aid future research because it shows the beginning of a conversion to better types of scaffolds. Currently, lots of research has been done on hydrogels because they are very biocompatible. This paper on the other hand shows why sponges could be a potential scaffold used for articular cartilage repair: such as their minimal contraction of gels and their minimal increase in MMP expression.
This is a really interesting article. I take it that the scaffolds are tested in vitro. It would be really interesting to do some sort of in vivo testing, maybe in rabbits to see whether these chondroyctes and the matrix can integrate with the native cartilage. The CARTICEL surgery sounds really interesting too, but looks very expensive. This might be a good way to heal damaged cartilage if the damage isn't too severe that it warrants a TKA.
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