Tissue engineering of meniscal cartilage

Fifty years ago it was shown that removal of a diseased meniscus in the knee joint led in the long term to cartilage degeneration and bone remodelling (Fairbank, 1948). This observation changed substantially the therapeutic approach adopted, with the ruptured meniscus being repaired instead of removed. However, this treatment is only feasible when the meniscal tissue is of good quality, which is often not the situation in the clinic. Concerns regarding disease transmission, immunogenicity, sizing, and availability of meniscal allografts have stimulated the search for a tissue-engineered (TE) structure that could replace the function of the native tissue. Previous studies have shown the relevance of fluid flow in the in vitro synthesis of cartilaginous tissues (Rotter et al., 1998). The constant availability of fresh media, the mechanical action of shear stress on the cells and the ability to transport nutrients through an increasingly dense extracellular matrix (ECM), are some of the reasons that favor the use of perfusion culture for the generation of bioartificial cartilage. However, optimal flow parameters for the generation of meniscal tissue have yet to be defined in such systems. We report here the use of perfusion culture and two powerful non-invasive techniques, magnetic resonance imaging (MRI) and spectroscopy (MRS), to characterize the flow profile inside a fixed bed bioreactor. the growth and energetics of the cells and the kinetics of ECM deposition. These techniques were used to correlate non-invasively the properties of the generated bioartificial meniscal cartilage with fluid dynamics and permeability measurements. An ideal flow rate for operation of the bioreactor (40 mlmin(-1)) was derived which optimises structural properties and ECM production.