Tissue engineering of the meniscus.
Buma, P, Ramrattan NN, van Tienen TG and Veth RPH. Biomaterials. 2004;25:1523-1532.
This is the editor's interpretation of a paper published in the orthopaedic literature in 2004 - our attempt to make relevant medical articles accessible to lay readers. If you wish to read the original it is easy to ask your librarian to obtain a reprint for you from any medical library.
The meniscus of the knee has a complex internal anatomy that is proving challenging to bioengineers and scientists in their attempts to engineer a replica that reproduces both the structure and the function of the meniscus.
The meniscus is composed of cells suspended within a matrix [Ed: like cherries in a cherry cake]. Within the matrix bundles of collagen are arranged to allow the meniscus to withstand and redirect the forces passing through the joint - compressive forces, shear stresses, circumferential forces and tensile hoop stresses. The cells of the meniscus develop during the embryo from primitive cells that later mature into identifiable meniscus cells. During this process, however, the cells and matrix of the inner thinner part of the meniscus where there are no blood vessels differ somewhat from the cells and matrix of the outer thicker part of the meniscus where there is a rich blood supply. The differences include -
- The inner tissue resembles fibro-cartilage tissue, while the outer tissue resembles fibrous tissue.
- The matrix within which the meniscal cells are suspended is largely composed of collagen, but again there is a difference between the outer part of the meniscus and the inner part in the exact chemical nature of the collagens and also in the presence of chemicals called glycosaminglycans (GAGs). [Ed: Although both regions are largely composed of what is known as type I collagen, there is a difference between the two regions in the amount of types II-VI collagens and GAGs, with the inner region being richer in these. The type I collagen is arranged circumferentially in bundles that absorb the weight of the body and prevent the meniscus from squashing outwards. The GAGs are important inasmuch as they maintain the hydration and elasticity of the meniscus, ensuring frictionless movement of the femur and tibia where they are in contact with the meniscus.]
The differences between the two regions of the meniscus - the thinner inner edge and the thicker outer rim - are relevant because most tears happen in the inner aspect where the blood supply is poor and tears do not heal spontaneously. In this inner region, although partial meniscectomy may relieve symptoms in the short term, in the long term load bearing and load distribution is compromised, leading to damage of the joint cartilage of the femur and tibia bones. For larger tears involving the outer region, if a total meniscectomy is performed it inevitably leads in time to severe joint cartilage degradation.
Tissue engineering may offer hope to people who have had or need partial or total meniscectomy, as it offers the possibility of filling in meniscal defects or completely replacing a meniscus that has been completely removed. What is meant by tissue engineering of the meniscus is that an artificial construct is made up from -
- a scaffold optimised to facilitate tissue ingrowth and differention (which is designed to break down naturally over time and eventually disappear)
- cells are encouraged to grow into the scaffold
- growth factors which stimulate the cells to differentiate into proper strong fibrocartilage
Scaffolds
The scaffolds which were being tried when this article was published included -
- whole tissues from elsewhere in the body, for example from around the bone. These have the disadvantage of having poor initial mechanical properties, but also they are unpredictable.
- isolated tissue components, for example collagens. These have the disadvantage of being not very strong so the implant needs considerable early protection, but the theoretical advantage is that the scaffold can break down and totally disappear once the cells that have grown into it start to make their own fibrocartilage, leaving the 'new' meniscus that results as strong and functional as the tissue it has replaced.
- completely synthetic polymer scaffolds, for example from the polyester family. These have the advantage that they can be manufactured to specific and predicable specifications, but the disadvantage is that degradation may lead to unwanted breakdown debris.
Cells
The cells used to populate the scaffold could be -
- synovial cells - the cells lining the inside of the joint cavity - which have shown the potential to migrate into a scaffold that has been sewn in to replace damaged meniscus.
- meniscus cartilage cells which can be harvested from the patient at the time of partial meniscectomy (freed by digesting the matrix away with digestive chemicals) and injected into a scaffold in a laboratory and encouraged to occupy the scaffold. The scaffold with its cells is implanted into the defect.
- stem cells - primitive cells from tissue culture from a different part of the patient's body - may be injected into the scaffold in a laboratory and again encouraged to grow in the scaffold before it is implanted into the patient to fill the defect.
Growth factors
Several growth factors are being explored that have varied potential to stimulate the cells to turn into fibrocartilage and produce the important GAG chemicals that give the meniscus much of its resilience and slipperiness. Other factors are being explored that may increase the amount of blood vessels supplying the meniscus rim.
This paper goes into a lot more detail for those of you interested in obtaining a copy from the library.