Computational analysis applied to the study of post-traumatic osteoarthritis

Post-traumatic osteoarthritis (PTOA) is a debilitating joint disease in which cartilage degenerates following joint trauma, including intra-articular fracture or ligament rupture. Acute damage and chronically altered joint loading have both been implicated in the development of PTOA, but the precise pathway leading from injury to cartilage degeneration is not yet known. A series of computational analyses were performed to gain insight into the initiation and progression of cartilage degeneration. Finite element models of in vitro drop-tower impacts were created to evaluate the local stress and strain distributions that cartilage experiences during such experiments. These distributions were compared with confocal imaging of cell viability and histologically apparent matrix damage. Shear strain and tensile strain both appear to correlate with the non-uniform percentage of cell death seen in the impact region. In order to objectively evaluate structural damage to the cartilage matrix, an automated image processing program was written to quantify morphologic characteristics of cartilage cracks, as seen in histology slides. This algorithm was used to compare the damage caused by different rabbit models of PTOA and to investigate the progression of matrix damage over time. Osteochondral defect insults resulted in more numerous and more severe cracks than ACL transection. Interestingly, no progression of structural damage was identified between 8 weeks and 16 weeks in these rabbit PTOA models.

A finite element based optimization algorithm was developed to determine cartilage material properties based on the relaxation behavior of an indentation test. This was then used to evaluate the spatial and temporal progression of cartilage degeneration after impact. Impacting cartilage with 2.18 J/cm2 through a metal impactor caused an immediate increase in permeability and decrease in modulus, both of which recover to nearly pre-impact levels within two weeks. Biologic testing suggests that the modulus changes were due to collagen fibril damage that is then repaired. Impacting with higher energy caused material softening that did not return to normal, suggesting an impact injury threshold below which cartilage had some ability to repair itself. To evaluate the effects of cartilage cracks on local stress and strain environments, finite element models of cracked cartilage were created. A physiologically-relevant, depth-dependent cartilage material model was developed and used to ensure accurate strains throughout the cartilage depth. The presence of a single crack was highly disruptive to the strain fields, but the particular shape or size of that crack had little effect. The most detrimental perturbations included two cracks within close proximity. When two cracks were within 0.5 mm of one another, the strain field between them increased in an additive fashion, suggesting a threshold for the amount of structural damage cartilage can withstand without being severely overloaded. The finite element models of cracked cartilage were also incorporated into an iterative degeneration simulation to evaluate the ability of mechanical loading to cause localized cartilage damage to spread to full-joint osteoarthritis.