Guide to mechanical characterization of articular cartilage and hydrogel constructs based on a systematic in silico...

Osteoarthritis is a whole joint disease with cartilage degeneration being an important manifestation. Tissue engineering treatment is a solution for repairing cartilage defects by implantation of chondrocyte-laden hydrogel constructs within the defect. In silico models have recently been introduced to simulate and optimize the design of these constructs. These models require accurate knowledge on the mechanical properties of the hydrogel constructs and cartilage explants, which are challenging to obtain due to their anisotropic structure and time-dependent behaviour. We performed a systematic in silico parameter sensitivity analysis to find the most efficient unconfined compression testing protocols for mechanical characterization of hydrogel constructs and cartilage explants, with a minimum number of tests but maximum identifiability of the material parameters. The construct and explant were thereby modelled as porohyperelastic and fibril-reinforced poroelastic materials, respectively. Three commonly used loading regimes were simulated in Abaqus (ramp, relaxation and dynamic loading) with varying compressive strain magnitudes and rates. From these virtual experiments, the resulting material parameters were obtained for each combination using a numerical inverse identification scheme. For hydrogels, maximum sensitivity to the different material parameters was found when using a single step ramp loading (20% compression with 10%/s rate) followed by 15 min relaxation. For cartilage explants, a two-stepped ramp loading (10% compression with 10%/s rate and 10% compression with 1%/s rate), each step followed by 15 min relaxation, yielded the maximum sensitivity to the different material parameters. With these protocols, the material parameters could be retrieved with the lowest amount of uncertainty (hydrogel: < 2% and cartilage: < 6%). These specific results and the overall methodology can be used to optimize mechanical testing protocols to yield reliable material parameters for in silico models of cartilage and hydrogel constructs.