Friday, March 21, 2008

Tissue Engineering of the Meniscus

The meniscus is crucial in bearing and distributing loads, absorbing shock, lubricating, and stabilizing the knee. Injuries to the meniscus are some of the most common injuries seen in orthopaedics and often lead to osteoarthritis and degradation of articular cartilage. More promising means to repair meniscal tears or synthesize an artificial meniscus are necessary, because the meniscus has a limited regenerative capability and injuries often occur in the interior, avascular region of the meniscus. Tissue engineering offers new treatment possibilities for meniscal repairs and replacements.

The phenotype of the meniscal tissue is similar to fibro-cartilage in the avascular region and is fibrous in the vascular region, consisting predominantly of type I collagen and glycosaminoglycans. Scaffolds that are biocompatible and biodegradable, allow unrestricted cell growth and free diffusion of nutrients, can be used as a carrier for growth factors, and maintain structural integrity while supporting the joint on the knee are qualifications for an ideal scaffold material. Scaffolds based on collagen molecules are the most promising, because of their optimal load-bearing capacity and the control of pore creation for new tissue ingrowth. Using whole tissues or isolated tissue components as scaffold material are often disadvantageous, because they cannot often bear large loads. The use of synthetic polymer-based scaffolds is currently being investigated because of the ability to control the porosity, the degradation rate, and other mechanical properties of polymers. In polymer design, the adhesive potential of the polymer scaffold to the host tissue is of key importance.

Other potential cells for investigation in scaffold associated studies involve nondifferentiated progenitor cells or fibroblasts, which have differentiated into fibro-cartilage-like cells in previous studies. Additionally, growth factors which stimulate synthesis and inhibit the degradation of the ECM have been studied for their effects on cultured meniscal cells or meniscus explants. Such growth factors include TGF-β, PDGF, IGF-I, which stimulate glycosaminoglycan production, proliferation of meniscal cells, and production of cartilage matrix molecules, respectively. As for replacing a meniscus with an autologous allograft, problems occur because of poor initial mechanical properties of the materials, preventing the allograft from lasting long-term. Donor menisci implants have associated problems, such as immunological reactions, disease transfer, and reshaping of the implant to fit the patient. More importantly, such implants often induce high friction in the knee joint, resulting in damage to the cartilage.

Meniscal injuries are exceedingly common in athletes, particularly soccer players and runners. If the meniscus degenerates or is removed, the remaining cartilage in the knee joint slowly wears away, leading to increasing pain in the joint, osteoarthritis, and severe joint degeneration. At this point, artificial joint replacement seems to be the most promising way to relieve the pain of osteoarthritis. However, there are numerous problems with this painful procedure, especially the length of time the implant lasts, usually around ten years, and the stresses on the bone that the implant places. Repairing the meniscus or offering new treatments using synthetic tissue engineering, provides these athletes with a remedy for their knee problems, enabling them to live with less pain, avoid artificial joint replacements, and possibly return to their sport. Currently recovering from my second meniscal tear, I am especially interested in new technologies and research into synthetic menisci and more effective treatments for meniscal repairs.

6 comments:

Terry D. Johnson said...

Kate,

Could you post a link to a useful paper or two in the comments?

Steven Law said...

Considering the relatively simple nature of meniscus relative to other tissues, how would this compare to an autologous ASC/ESC-generated meniscus? What about xenografts? Would this method be more of a long-term solution or a standby until other sources of transplants mature?

RagingNanite said...

So you mentioned that possible treatments would be for athletes, but I was wondering more about the general population. Is age related damage similar enough to the damage caused by athletic competition to use the same technique to treat it?

Kate Liddle said...

Here are some interesting papers that go into more detail regarding specific scaffolds, scaffold-cell interactions, and assessments of the scaffolds.

The Effect of Growth Factor Treatment on Mensical Chondrocyte Proliferation and Differentiation on Polyglycolic Acid Scaffolds.
http://www.liebertonline.com/doi/pdfplus/10.1089/ten.2006.0242

Growth Factors and Fibrochondrocytes in Scaffolds
http://www3.interscience.wiley.com/cgi-bin/fulltext/112218998/PDFSTART

Comparison of Scaffolds and Culture Conditions for Tissue Engineering of the Knee Mensicus
http://www.liebertonline.com/doi/pdfplus/10.1089/ten.2005.11.1095

Kate Liddle said...

Steven,

Stem cells have been used in the development of artificial menisci but are often seeded on some sort of scaffold to direct the growth and morphology of the tissue. The major problem with autologous ASC or ESC-generated menisci or other menisci of autologous material involves introducing the material into the joint, which requires a great amount of friction and can damage the implant. As for xenografts or allografts, several problems arise. Preservation techniques are often difficult and can be expensive, transfer of diseases are possible along with immunological reactions, and individual reshaping of the implant is necessary. In a fair number of cases, the implant does not survive, especially in a knee with evidence of arthritis. A xenograft would serve as a short-term solution to a meniscal repair, prolonging arthroplasty for an average of 5 to 10 years (http://www.stoneclinic.com/meniscus_latest.htm).

Kate Liddle said...

Austin,

Athletic-related injuries often involve meniscal tears that can sometimes be treated with meniscal repair, as opposed to meniscal removal. As for age-related damage, general meniscal wear in commonly seen and is currently treated by performing a meniscectomy. The techniques investigated in this paper and other methods of meniscal regeneration are geared toward treating both age-related damage and athletic damage in the same manner.