Background

Fretting at modular junctions is thought to be a ‘mechanically assisted’ corrosion phenomenon, initiated by mechanical factors that lead to increased contact stresses and micromotions at the taper interface. We adopted a finite element approach to model the head-taper junction, to analyse the contact mechanics at the taper interface. We investigated the effect of assembly force and angle on contact pressures and micromotions, during loads commonly used to test hip implants, to demonstrate the importance of a good assembly during surgery.

Hyaline cartilage defects are a significant clinical problem for which a plethora of cartilage repair techniques are used. One such technique is cartilage replacement therapy using autologous chondrocyte or mesenchymal stem cell (MSC) implantation (ACI). Mesenchymal stem cells are increasingly being used for these types of repair technique because they are relatively easy to obtain and can be expanded to generate millions of cells. However, implanted MSCs can terminally differentiate and produce osteogenic tissue which is highly undesirable, also, MSCs generally only produce fibrocartilage which does not make biomechanically resilient repair tissue, an attribute that is crucial in high weight-bearing areas. Tissue-specific adult stem cells would be ideal candidates to fill the void, and as we have shown previously in animal model systems [Dowthwaite et al, 2004, J Cell Sci 117;889], they can be expanded to generate hundreds of millions of cells, produce hyaline cartilage and they have a restricted differential potential. Articular chondroprogenitors do not readily terminally differentiate down the osteogenic lineage.

At present, research focused on isolating tissue-specific stem cells from articular cartilage has met with modest success. Our results demonstrate that using differential adhesion it is possible to easily isolate articular cartilage progenitor populations from human hyaline cartilage and that these cells can be subsequently expanded in vitro to a high population doubling whilst maintaining a normal karyotype. Articular cartilage progenitors maintain telomerase activity and telomere length that are a characteristic of progenitor/stem cells and differentiate to produce hyaline cartilage.

In conclusion, we propose the identification and characterisation of a novel articular cartilage progenitor population, resident in human cartilage, which will greatly benefit future cell-based cartilage repair therapies.

One reason why NICE (National Institute for Clinical Excellence) does not support operations by the NHS to heal hyaline cartilage lesions using a patients own cells is because there is no clear evidence to show that these operations are beneficial and cost-effective in the long term. Specifically, NICE identified a deficiency of high quality cartilage being produced in repaired joints. The presence of high quality cartilage is linked to long-lasting and functional repair of cartilage. The benchmark for quality, NICE stipulate, is repair cartilage that is stiff and strong and looks similar to the normal tissue surrounding it, i.e. mature hyaline articular cartilage.

Biopsy material from autologous cartilage implantation surgical procedures has the appearance of immature articular cartilage and is frequently a mixture of hyaline and fibrocartilage. Osteoarthritic cartilage, in its early stages, also exhibits characteristics of immature articular cartilage in that it expresses proteins found in embryonic and foetal developmental stages, and is highly cellular as evidenced through the presence of chondrocyte clusters. Therefore, an ability to modulate the phenotype and the structure of the extracellular matrix of articular cartilage could positively affect the course of repair and regeneration of articular cartilage lesions. In order to do this, the biochemical stimuli that induce the transition of an essentially unstructured amorphous cartilage mass (immature articular cartilage) to one that is highly structured and ordered, and biomechanically adapted to its particular function (mature articular cartilage) has to be identified.

We show for the first time, that fibroblast growth factor-2 and transforming growth factor beta-1 induce precocious maturation of immature articular cartilage. Our data demonstrates that it is possible to significantly enhance maturation of cartilage tissue using growth factor stimulation; consequently this may have applications in transplantation therapy, or through phenotypic modulation of osteoarthritic chondrocytes in diseased cartilage in order to stimulate growth and maturation of repair tissue.