Dynamic stiffness of articular cartilage and potential repair materials

Cartilage has limited potential for self repair. Therefore, articular cartilage lesions often lead to early osteoarthritis. Early clinical results of cartilage replacement procedures such as autologous matrix-induced chondrogenesis (AMIC) seem promising, but long term results are not available to date. Only longitudinal studies of 20 years and more will show whether the cartilage repair procedures currently in evaluation will prevent the treated patients from developing early osteoarthritis and if the progression of osteoarthritis will be halted. In order to be able to evaluate and compare different methods of cartilage treatment, a thorough understanding of the mechanical properties of intact cartilage and cartilage with early degenerations is needed.
The prime function of cartilage is load bearing. Cartilage absorbs and spreads the applied energy thereby protecting the underlying bone. It also provides diarthrodial joints with an almost frictionless gliding surface. It has been shown in clinic that there is a correlation between the histological quality, the load bearing capacity and the durability of the repair. Thus it seems logical to search for a repair with properties close to that of normal cartilage.
The mechanical behaviour of cartilage is complex, since the tissue structure is a combination of partly porous, viscous and elastic components. This results in deformation rate-dependent stiffness, i.e. how much energy is needed to deform the cartilage (dynamic modulus) and energy dissipation (loss angle) properties. The water movement through or out of the cartilage under a given loading condition makes its response to loading more complex compared to an ordinary viscoelastic solid. To determine these properties, several tests can be performed, i.e. unconfined or confined compression, or indentation tests. In this thesis, dynamic indentation tests were performed because indentation minimizes specimen preparation and has been shown by others to produce meaningful cartilage stiffness data. However, a mathematical model is needed to calculate stiffness data out of those experiments. These models are always a simplification of the real situation, since cartilage is a complex structure with complex mechanical properties. To determine the influence of the mathematical model used on the results the conventional model (Hayes) is compared with a novel method (Kren) in chapter 2, which has as a main advantage that it does not assume linear elasticity. Although a difference was found in absolute values calculated with these models, the trends they show were similar when used to evaluate the same set of data. Thus experimental data cannot be compared between these different models, but for comparisons within one model, both models give similar results.
In order to determine cartilage behaviour, preferably healthy human specimens are tested. Unfortunately, these specimens were extremely difficult to obtain. Therefore in chapter 3, we investigated whether swine cartilage could serve as a model for human cartilage for mechanical testing. At equivalent anatomic locations, dynamic modulus was similar for human and swine specimens, but a small difference was found in the loss angle. Keeping these differences in mind, swine specimens can be used for ex-vivo testing.
Since mechanical behaviour of cartilage depends on the applied deformation rate and inter- and intra-individual heterogeneity, in chapter 3 the behaviour of cartilage in swine knee joints was determined as a function of loading mode and anatomic location. We observed a larger heterogenity at fast compared to slow deformation rates. Moreover, no differences were found in the loss angle at slow deformation rate between locations. These differences highlight the need for using multiple test modes, i.e. loading cartilage at different strain rates.
After expanding the knowledge of dynamic stiffness properties of cartilage, in chapter 4 and 5 we explored whether double network hydrogels (DN-gels) are suitable as a cartilage repair material. It already has been shown by others that these DN-gels look promising to serve as a cartilage repair material because of its low sliding friction, high wear resistancy, high thoughness and biocompatibility. Current focal repairs have a much lower initial stiffness and strength than the surrounding tissue, which increases early failure potential. In chapter 4, we tested the mechanical properties related to surgical use of two kinds of DN-gels. Both DN-gels showed good suture tear-out strength and also pull-off tests with tissue adhesive showed promising results. However, dynamic stiffness of both DN-gels was only about 10% of cartilage stiffness and also its loss angle was much lower.
To increase the potential of these DN-gels as cartilage repair material, its stiffness has to be increased. To achieve this, we adapted the stiffness of one of the two DN-gels tested in chapter 4 by altering the water content in chapter 5. The dynamic modulus increased with decreasing water content. No difference in the loss angle was found in slow deformation whereas in fast deformation loss angle was higher in DN-gels with lower water content. The DN-gel with lowest water content had higher stiffness in slow deformation and lower stiffness in fast deformation compared to native cartilage. This difference is caused by the lower loss angle of this DN-gel. Overall it looks promising that DN-gel stiffness can come close to that of native cartilage. However, loss angle differences should be further investigated.
In summary, cartilage is a complex structure and it was shown that not only stiffness, but also energy dissipation is an important mechanical parameter. Both parameters should be investigated at multiple deformation rates to get a complete picture of cartilage mechanics. Also, healthy swine cartilage was shown to be a reasonable substitute for human cartilage in dynamic stiffness evaluations. Finally, DN-gels look promising to serve as a cartilage repair material, since they have good surgical handling properties and their stiffness is close to that of native cartilage.