CHRONIC ALTERED JOINT KINEMATICS AND CARTILAGE DEGENERATION AFTER 6 MONTHS IN A LARGE ANIMAL MODEL OF MENISCUS INJURY

Introduction:: The link between meniscus injury and osteoarthritis (OA) is well-known [1,2], but the progression of meniscus changes and the inter-relationship between cartilage and meniscus degeneration remain unknown. Altered joint loading is hypothesized as a catalyst for OA development, so our group recently established a large-animal porcine model of meniscus injury that unloads the meniscus and replicates progressive knee joint changes [3,4]. We found, via TEKSCAN pressure sensors on the tibial plateau, an increase in peak load and decrease in contact area at one month, however these changes returned to near-normal levels at six months [4]. While promising, this study was limited by insertion of the pressure sensors, which disrupted the joint capsule, and an injury that was a simple cut through the horn attachment that may have endogenously remodeled (whereas the human meniscus attachment injury does not). In this study, we have addressed these limitations by developing a magnetic resonance imaging (MRI)-based method to quantify joint kinematics in an intact joint and applied a more aggressive en bloc resection of the horn attachment. Therefore, the objective of this study was to evaluate joint kinematics and cartilage degeneration at 6 weeks and 6 months following meniscus horn injury in a porcine model. Establishing the time-dependent relationships between joint kinematics, meniscus function, and cartilage OA will provide insight into key mechanisms of disease and provide rationale for improved treatments for meniscus injury.


Materials and Methods:: Yucatan minipigs (12-month-old, ~50-60 kg) underwent knee surgery and en bloc removal of a 5 mm section of the medial meniscus anterior attachment. Animals were euthanized at 6 weeks (n=8) or 24 weeks (6 months; n=4) post-op and the contralateral knee was an intact control. Immediately after sacrifice, knees were scanned with a T₂-weighted CPMG sequence and cartilage T₂ times were calculated. Joint kinematics were quantified using a custom MRI-compatible loading device that compressed the joint at 30° flexion at 50 N (Preload) and 510 N (Full Load) [5]. T1-VIBE MRIs were acquired at both the Preload and Full Load, and meniscus kinematics were calculated by image registration between loads. After MRI, joints were dissected, and tibial plateau osteochondral samples collected for mechanical testing. Cartilage indentation testing was performed at four locations: two cartilage regions previously covered by the meniscus (C-M), and two uncovered cartilage-cartilage regions (C-C). Creep tests were fit to a Hertzian biphasic creep model to quantify compressive modulus, tensile modulus, and permeability [6]. All data was compared with two-way ANOVA to test the effect of treatment and time, followed by post-hoc Tukey HSD to compare pairs of results. Significance was set at p< 0.05.




Results, Conclusions, and Discussions:: All animals tolerated the surgery well. The 24 week cohort exhibited consistent mild-moderate lameness on the operated leg at a trot. For both timepoints, under applied Load the Injured meniscus rotated within the axial plane, pivoting about the posterior attachment (Fig 1). The Intact meniscus displacement with Load (gray arrows in Fig 2) was 0.3-0.5 mm in the medial direction and 0.7-1.0 mm in the anterior direction and did not change significantly with time. The Injured meniscus initial position (at Preload, red dots in Fig 2) at 6 weeks started nearly 2 mm medial of the initial position of the meniscus in Intact joints (p< 0.05); the anterior position was unchanged. At 24 weeks, this initial position (at Preload) started only 0.8 mm medially and 0.5 mm posteriorly to the Intact position. With Load, the Injured meniscus (red arrows in Fig 2) at 6 weeks moved 0.8 mm anteriorly and 0.2 mm medially and at 24 weeks moved 1.0 mm anteriorly and 0.2 mm medially. There were no statistical differences between 6 weeks and 24 weeks for the Injury group. These joint changes following meniscus injury suggest a chronic altered joint structure and loading.

In the cartilage, the quantitative T₂ time in the C-C region trended higher in the Injury compared to Intact at both time points (p=0.08 and 0.10, Fig 3), with no significant difference with post-op time, indicating degeneration in the C-C region. There were no significant differences in the C-M region. From the cartilage indentation tests, tensile and compressive moduli in the Injured group were significantly decreased compared to the Intact group in the C-M region (p< 0.01, Fig 4A,B), but post-hoc tests did not reveal significance between individual groups. There was no significant difference with post-op time. The moduli did not change in the C-C region. However, in the C-C region, the cartilage permeability was higher in the Injury compared to the Intact group (p=0.003), and did not change with time post-op.

In summary, this study demonstrated altered joint kinematics following meniscus injury that were chronic over 24 weeks and associated with degenerative cartilage changes.


Acknowledgements (Optional): : This work was supported by the NIH and the Department of Veterans Affairs.


References (Optional): : [1] Glasson, S et al., Osteoarthr. Cartil., 15(9):1061-9, 2007.

[2] Roos, H et al., Osteoarthr. Cartil., 3(4):261-7, 1995.

[3] Bansal, S et al., J Orthop. Res., 38(12):2696-2708. 2020.

[4] Bansal, S et al., Tissue Engineering Part C: Methods, 23(11):661- 672. 2017.

[5] Meadows, K et al., J Biomech., in press. 2023.

[6] Moore, A et al., J Tribol., 138(4): 041405. 2016.