Building Cartilage Scaffolds the Microfluidic Way

Cartilage

Our bodies are pretty much amazing. We can get hurt, and our bodies will heal our cuts and bones (with the right support). But not everything heals so easily, like cartilage. The cartilage in our joints is called hyaline cartilage and can be damaged from trauma or diseases like osteoarthritis. The other cartilages like elastic cartilage (found in our ears and nose) and fibrocartilage (found on tendons and ligaments) are a bit of a different story. The hyaline cartilage found on the articular surfaces of our bones can't heal like other parts of our body because it doesn't contain any blood vessels. The blood vessels would normally provide the cells and proteins to the damaged tissue. So, without blood, the damaged tissue pretty much does, nothing. Enter tissue engineering.

Cartilage Engineering

When faced with something that won't fix itself, our initial impulse is to replace it. That was our first reaction too, but we can't replace cartilage with just anything. It is a very complex and dynamic tissue. Ideally we would replace it with fresh cartilage, but it's not so easy to grow. The engineered cartilage must have a functional shape, achieve specific mechanical properties and not cause an immunogenic response when implanted in the body. In order to encourage cartilage cells (called chondrocytes) to form tissue in three dimensions instead of the two-dimensional bottom of a dish, tissue engineers have been developing scaffolds. Scaffolds have four desired traits:

  • Highly porous with interconnected network for cell growth and transport of nutrients and metabolic waste
  • Biocompatible and bioresorbable so that it can be replaced by the tissue
  • Ideal surface for cell attachment and proliferation
  • Mimic cartilage mechanical properties

 

Alginate (source) 

Alginate (source) 

Choosing the right material is pretty important, but devising a way to create a porous 3D network is also vital. Cells can't be cut off from transport of nutrients and waste, even though it's crazy to believe that chondrocytes only make up 1% of the volume in cartilage. Researchers at National Taiwan University have developed a new method to build cartilage scaffolds using a polymer called alginate, which is a gum extracted from seaweed. It has been used previously in other scaffolds, but the main advance made by the researchers is how it is manipulated.

 

Microfluidic-generated Scaffold

Scaffold_Microfluidic_Setup.jpg
Honeycomb Alginate Scaffold

Honeycomb Alginate Scaffold

The work by Feng-Huei Lin et al. is entitled "A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology" and appears in the October issue of Biomaterials. The authors have developed a novel microfluidic method for creating the alginate-based scaffold. As depicted in their figure, alginate droplets are formed around nitrogen gas. Their formation is highly controlled resulting in monodisperse droplets, which means that they're all (statistically) the same in size and shape. These droplets fall from the device into a solution containing calcium ions. The calcium ions (Ca2+) cause the alginate to form a gel. But before that happens, the droplets form a pretty honeycomb pattern. While this looks nice, it has a very important function. Remember when I said that scaffolds need to have interconnected networks? Well the monodisperse droplets are able to align so that they fit together perfectly, creating hexagonal patterns around each droplet. Once the droplets have gelated, a vacuum is applied which removes the air bubbles and connects the network.

This technique has seen some promising results when looking at how the cells attach, proliferate and survive. But some forms of alginate have been known to cause immunogenic responses which would be unattractive. Any resulting engineered tissue would need to be mechanically tested, which was not performed in this study.

Overall, this research was pretty interesting. It's obviously relevant to us humans, but it also excites me because it is a form of therapeutic microfluidics. As you can see from the rest of my posts, a lot of microfluidic technology is used in diagnostics. Both are equally important, but occur in different frequencies, so you can understand why this would have a place in my heart.

Note: For more information on tissue engineering, check out Nova's great episode on it, Replacing Body Parts.

 

References:

Hutmacher, D. (2000). Scaffolds in tissue engineering bone and cartilage Biomaterials, 21 (24), 2529-2543 DOI: 10.1016/S0142-9612(00)00121-6

Temenoff, J., & Mikos, A. (2000). Review: tissue engineering for regeneration of articular cartilage Biomaterials, 21 (5), 431-440 DOI: 10.1016/S0142-9612(99)00213-6

Wang, C., Yang, K., Lin, K., Liu, H., & Lin, F. (2011). A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology Biomaterials, 32 (29), 7118-7126 DOI: 10.1016/j.biomaterials.2011.06.018