Fight Aging!

Regrowth and replacement of age-damaged cartilage is one of the obvious candidates for early applications of tissue engineering. It tends to be most in need of treatment in non-vital parts of the body, such as joints, and is not as evidently complicated to work with from a surgical point of as, say, a major organ such as the heart or liver. Which is all a way of saying that it should cost less to get underway, while failures should be nowhere near as likely to cause enormous harm to patients in trials or undergoing eventual treatments. It is not a terrible approach to start at the shallow end of the difficulty pool and work into deeper waters once that is going well.

Unfortunately cartilage is tremendously complicated at the small-scale level of proteins and tissue structure. If you throw a bunch of cartilage cells into even a sophisticated bioreactor and grow them, then the result is a pseudo-tissue that bears little resemblance to real cartilage. The most important aspects of cartilage are its mechanical properties, such as the ability to bear load, for example. These arise from the fine structure of cartilage extracellular matrix (ECM), arrangements of cells, and relationships between proteins, and getting that right has proven to be a challenge. It is only recently that some researchers claim to have produced cartilage tissue that does begin to measure up.

This open access review paper covers attempts in past years to build nanoscale-featured scaffold materials to guide cartilage regrowth. Such a scaffold is a partial replacement for the extracellular matrix in living tissue, and in an ideal situation would be digested and replaced with real extracellular matrix by the cells that colonize it. This approach has shown considerable promise for the engineering of other tissues, such as bone, skin, and muscle. Efforts to make it work for cartilage have so far met with limited success, however, and for the reasons noted above.

Nanotechnology Biomimetic Cartilage Regenerative Scaffolds

There are three different forms of cartilage in the body: hyaline, elastic and fibrous cartilage. Each can be found in specific sites and with different properties and functions. Hyaline cartilage can be found in the joints, nose, trachea and ribs. To date, detailed cartilage regeneration studies of human hyaline cartilage have been predominantly focused on articular cartilage. This has been driven by the volume of demand related to degenerative osteoarthritis. Articular cartilage samples have been more widely available to science due to the prevalence of joint replacement surgery. Nonetheless, the fundamental principles and advances of cartilage regeneration derived from articular cartilage studies provide a template for the engineering of head and neck cartilage.

Tissue engineering has advanced over the past two decades and continues to evolve in search of optimal tissue replacements alongside nanotechnology. The concept and results of mimicking the structure and function of the natural ECM form the current direction of travel for the fabrication of an optimal tissue regenerative scaffold.

Although the results of current studies have been encouraging, further refinements need to be made. As active growth factors used in current studies are inevitably subjected to contact with organic solvents or time-consuming procedures during processing and scaffold fabrication, it is likely that the majority of the growth factors are denatured. Uncompromised delivery of any growth factor at an optimal concentration with precise release kinetics is ideally required to translate growth factor delivery from an in vitro to in vivo level for tissue regeneration. A system of cell-mediated activation of available bioactive molecules may provide a breakthrough. This might be achieved by incorporating the latent form of the desired protein into the scaffold design. The incorporation of nanotechnology and bioactive cues into tissue scaffold design should prove increasingly promising in cartilage engineering.

Many research studies in cartilage tissue engineering often focus on specific areas of interest with encouraging results, but these studies often lack the holistic requirements to produce a successful tissue replacement. Thus, a multidisciplinary collaborative approach which includes specialised stem cell culture, nanotechnology and bioactive cues, materials science, environmental and mechanical stimulation, and bioreactor culture as well as vascular tissue engineering may offer a breakthrough in functional cartilage regeneration.