Cartilage tissue engineering and bioreactor systems for the cultivation and stimulation of chondrocytes

It is believed that the function and structure of cartilage is directed and maintined by the mechanical forces placed upon it, helping in part to create the stratification shown in fig. (a). This figure can be found in their original context in the paper linked to above.

Summary:
This article examines the growth and cultivation of chondrocyte cells for therapeutic uses in humans, with a focus on the design of bioreactors that can (at least partially) recreate the physical forces experienced by such cells in vivo, which are believed to affect their functionality. Chondrocytes are the type of cells that make the different kinds of cartilage in the human body. Cartilage itself is primarily composed of a complex ECM designed to resist different kinds of forces depending on its type and location. Articular cartilage in particular has the lowest volumetric cell density in the human body (99% ECM by volume), and is practically avascular, relying on diffusion and the movement of synovial fluid. Additionally, it must be able to withstand and absorb forces equal to several times a person’s body weight (particularly true of the articular cartilage in the hip and knee). These factors make it very difficult and slow for cartilage to heal itself, and sufficient damage can make self-repair impossible, emphasizing the desire for engineered cartilage tissue that can replace the damaged regions. Articular cartilage is thin and can survive reasonably hypoxic environments, side-stepping the vascularization problem of most engineered tissues; however, merely growing chondrocytes in collagen gels is not enough – the tissues structure and function are highly influenced by the dynamic processes it is subject to in the body, including hydrostatic pressure, compression, and other mechanical stimuli. The second half of the paper focuses almost entirely on different types of bioreactors that have been created to explore solutions to these issues by subjecting chondrocytes to these forces in a multitude of different manners, both statically (applying a constant force) and dynamically (varying the force, more closely approximating the natural environment). It ends with a discussion of using something like a ‘bedside bioreactor’ to grow cartilage implants from a patient’s own stem cells, but makes the point that before such devices are viable, more research must be done on the process of chondrocyte differentiation and the role mechanical forces play in it.

Significance:
One line from the paper underlines the societal importance of chondrocyte tissue engineering: “Currently, more than 40 million US American citizens (approximately 15% of the overall population of the USA) suffer from arthritis. It is estimated that nearly 60 million US American citizens will be affected by the year 2020.” That is a considerable portion of the population whose lives could be improved through the use of engineered cartilage tissue. The importance of mechanical and biological components seems to make this a task well suited to bioengineering. In addition, articular cartilage benefits from not being complicated by the need for a method of vascularization that beleaguers thicker tissues, increasing the chances that a method for the effective culturing of implantable cartilage tissue could be found in the near future.
(And on a merely personal note, having had surgery that involved removing a chunk of cartilage from my knee, I think it would be really great if we could develop something that could repair it before the bones in my knee wear out!)