Direct noninvasive measurement and numerical modeling of depth-dependent strains in layered agarose constructs.

Biomechanical factors play an important role in the growth, regulation, and maintenance of engineered biomaterials and tissues. While physical factors (e.g. applied mechanical strain) can accelerate regeneration, and knowledge of tissue properties often guide the design of custom materials with tailored functionality, the distribution of mechanical quantities (e.g. strain) throughout native and repair tissues is largely unknown. Here, we directly quantify distributions of strain using noninvasive magnetic resonance imaging (MRI) throughout layered agarose constructs, a model system for articular cartilage regeneration. Bulk mechanical testing, giving both instantaneous and equilibrium moduli, was incapable of differentiating between the layered constructs with defined amounts of 2% and 4% agarose. In contrast, MRI revealed complex distributions of strain, with strain transfer to softer (2%) agarose regions, resulting in amplified magnitudes. Comparative studies using finite element simulations and mixture (biphasic) theory confirmed strain distributions in the layered agarose. The results indicate that strain transfer to soft regions is possible in vivo as the biomaterial and tissue changes during regeneration and maturity. It is also possible to modulate locally the strain field that is applied to construct-embedded cells (e.g. chondrocytes) using stratified agarose constructs.

Noninvasive dualMRI-based strains vary by depth and region in human osteoarthritic articular cartilage.

OBJECTIVE: To noninvasively assay the mechanical and structural characteristics of articular cartilage from patients with osteoarthritis (OA) by magnetic resonance imaging (MRI), and to further relate spatial patterns of MRI-based mechanical strain to joint (depth-wise, regional) locations and disease severity. METHODS: Cylindrical osteochondral explants harvested from human tissue obtained during total knee replacement surgery were loaded in unconfined compression and 2D deformation data was acquired at 14.1 T using a displacements under applied loading by MRI (dualMRI) approach. After imaging, samples were histologically assessed for OA severity. Strains were determined by depth, and statistically analyzed for dependence on region in the joint and OA severity. RESULTS: Von Mises, axial, and transverse strains were highly depth-dependent. After accounting for other factors, Von Mises, axial, and shear strains varied significantly by region, with largest strain magnitudes observed in explants harvested from the tibial plateau and anterior condyle near exposed bone. Additionally, in all cases, strains in late-stage OA were significantly greater than either early- or mid-stage OA. Transverse strain in mid-stage OA explants, measured near the articular surface, was significantly higher than early-stage OA explants. CONCLUSION: dualMRI was demonstrated in human OA tissue to quantify the effects of depth, joint region, and OA severity, on strains resulting from mechanical compression. These data suggest dualMRI may possess a wide range of utility, such as validating computational models of soft tissue deformation, assaying changes in cartilage function over time, and perhaps, once implemented for cartilage imaging in vivo, as a new paradigm for diagnosis of early- to mid-stage OA.