Comparison of Scaffolds and Culture Conditions for Tissue Engineering of the Knee Meniscus
The meniscus of the knee is mostly avascular and incapable of regeneration. Thus, meniscal injuries are often permanent. Currently there is no widely accepted treatment. Tissue engineering of the meniscus provides a potential solution.
Agarose is commonly used in tissue engineering because it is easy to mold and seed with cells. Both fibroblasts and chondrocytes have been shown to proliferate on poly(glycolic acid) (PGA). Furthermore, studies using PGA in rotating wall bioreactors have demonstrated increased synthesis of chondrocytes. The authors of this study compared the growth and proliferation of fibrochondrocytes on agarose and PGA in static cultures and rotating wall bioreactors.
Fibrochrondrocytes were harvested from menisci of adult rabbits and seeded on agarose and PGA. Cells were allowed to attach to their respective scaffolds for a week in a static culture. Some scaffolds were then place in a rotating wall bioreactor for another six weeks. Histology was performed to visualize the distribution of collagen and glycosaminoglycan (GAG). Samples were assayed for total GAG and collagen content.
This study showed that fibrochondrocytes grew significantly better in PGA compared to agarose in both the static cultures and rotating wall bioreactors. There was no significant difference between PGA static cultures and PGA rotating wall bioreactors. Cells in PGA also had higher GAG and collagen content than in agarose. From this study, PGA is clearly a more suitable scaffold for tissue engineering of the meniscus.
I found this study interesting because the authors sought to find a suitable scaffold to use before throwing growth factors at the samples. Providing the cells with the appropriate environment and conditions to proliferate seems more important to me than adding a bunch of "extra stuff" that may or may not do anything. The knee undergoes a lot of compressive stress. I think it would be interesting if the authors also compared the cellular response in each scaffold to an applied force. The authors did perform mechanical tests to determine the modulus of each sample, but I think the difference in moduli is due to the material properties of the scaffold.
6 comments:
One of the most important issues about knee caps is regeneration, or lack there of. You bring up a good point that we need to see whether the cells are inherently capable to attach to the scaffold. Sometimes, unlike in this case, several factors are needed in order to facilitate some process, but this paper demonstrated the minimal components for the cell attachment for this particular case. What I want to know is why did the PGA rotating bioreactor resulted in no difference when compared to the PGA static cultures?
I was also curious if the authors explained why there wasn't improved cell growth in the bioreactor. If in earlier studies, a bioreactor with a PGA scaffold improved cell growth, why not in this case?
I'm trying to think of ways in which one would be able to transplant an artificial meniscus in vivo. Would they just replace the entire site or only parts of the site? Or could they just remove the damaged part add in the ECM, in this case PGA, and implant stem cells? Finding new ways to create scaffolds for tissue development is imperative we, as tissue engineers, hope to create viable tissues for transplant.
Providing the cells with the appropriate environment and conditions to proliferate seems more important to me than adding a bunch of "extra stuff" that may or may not do anything.
Or, perhaps even worse, growth factors that may do something when the cells are on TC plastic, but may not do that same thing in a device.
After 3 weeks, the PGA bioreactor showed a significantly greater cell number than in the static culture. However, by the end of the experiment at week 7, the number of cells in the bioreactor dropped below the static culture. The authors explained the loss of cells due to washing of the bioreactor.
Figure 6 shows that cells in the PGA bioreactor produced less GAG than in the static culture. I question the graphs because the y-axis is GAG per scaffold. Since the bioreactor had fewer cells, the amount of GAG would also be lower. Maybe they should have normalized the results somehow.
Just as you brought up, now that the evidence suggests that there is significantly better fibrochondrocyte growth in PGA as compared to agarose, the next step is to calculate cell performance .
Will there also be better mechanical response in material to repeated compressive loading? Even thermal response from the friction experienced must be calculated.
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