In Vivo Assessment of Passive and Active Articular Cartilage Strain Recovery

Introduction::
Articular cartilage lines the ends of long bones in synovial joints and functions to provide load-bearing and low-friction articulation. These biomechanical functions are largely driven by the poroelastic mechanics (fluid pressurization) of the articular cartilage [1]. Unfortunately, the same poroelastic pressure that leads to load-bearing and lubrication also drives fluid exudation and concurrent tissue strain. In vivo static loading (e.g., standing) produces as much as -30% strain in 60 min. Interestingly, active loading (e.g., walking, knee bends, cycling, running) in vivo produces an initial period of fluid exudation and strain (~ -5%) [2]; after which, active loading arrests further fluid loss and tissue strain [3]. While static and active loading drive fluid exudation and cartilage strain, static unloading (e.g., lying down) provides recovery, and to date, is the only in vivo mechanism that has been shown to restore hydration and strain.




We hypothesize that active loading is actually a hydration and strain recovery mechanism that has yet to be observed. In this study, we investigate whether active loading (walking) is only an exudation and arresting mechanism or whether it is also capable of recovery. We use magnetic resonance imaging (MRI) to evaluate the in vivo strain of articular cartilage in human knees following: (1) standing (static loading), (2) lying down (static unloading), and (3) walking (active loading).




Materials and Methods::
Participants. Following IRB approval, we recruited N=8 asymptomatic young adults to participate in the study. Participant age (29 ± 3 years of age, mean ± 95% confidence interval), biological gender (4 male, 4 female), and BMI (23 ± 2) were recorded. Up to 5 days prior to MRI scanning, participants were given a wrist worn activity monitor to track the number of steps taken each day (13 ± 5k steps/day). Knee joint health was assessed using the self-reported Knee Injury and Osteoarthritis Outcome Score (KOOS).




MRI Scanning. Participants arrived at the MRI facility on the day of scanning and were positioned within the scanner (3T MAGNETOM Prisma, Siemens) with a 15 channel Tx/Rx knee coil around their right knee. Participants were scanned in the following fixed order: (1) baseline, and immediately after (2) 30 min of standing, (3) walking for 10 min at 110 steps per min, (4) 30 min of standing, and (5-8) 12, 24, 36, and 48 min of lying down (Fig 1). A proton density weighted turbo spin echo (PD-TSE) was used to assess the morphology and thickness of the articular cartilage.




Data Analysis. We calculate cartilage thickness as the tibiofemoral bone-to-bone distance within the medial and lateral compartments, measured within the region of contact. MRI scans were registered to the baseline scan to ensure the same region was measured. We calculate cartilage strain as the change in cartilage thickness divided by the baseline thickness. All values are reported as the mean ± 95% confidence interval.




Results, Conclusions, and Discussions::
The average strain in the medial and lateral compartments for 8 participants are shown in Fig 2A&B. After 30 min of static loading (standing), there is a clear thinning of the articular cartilage to an average -5.0 ± 0.4 and -5.3 ± 0.6% strain in the medial and lateral compartments. Following a 10 min walk (active loading), the cartilage thickness recovers 2.3 ± 0.3 and 2.6 ± 0.6% strain, which directly agrees with our hypothesis that active loading is capable of recovery. Following another bout of static loading to approximately the same strain (-5.4 ± 0.3 medial and -5.1 ± 0.5% lateral) the participant lies supine (static unloading), and the cartilage thickness and strain progressively recover. Following the first scan (12 min post standing), the cartilage recovered 1.5 ± 0.6 and 1.1 ± 1.0% strain in the medial and lateral compartments. Following 48 minutes of unloaded recovery the cartilage recovered 3.8 and 3.6% strain in the medial and lateral compartments.




In agreement with prior literature, static loading causes cartilage strain [4] while static unloading causes strain recovery [3]. These dynamics are driven by fluid flow out of and into the articular cartilage [5]. Counter to the existing literature, we have shown that active loading (walking) is not simply an exudative and arresting mechanism [3,6] but also a mechanism of recovery, which we hypothesize is driven by fluid flow back into the articular cartilage. In future work, we will further assess the flow of fluid using T2-w imaging.




The implication for activity driven cartilage recovery is significant. While epidemiological studies have documented the chondroprotective nature of joint activity, we have yet to identify the mechanism that provides chondroprotection. The observation that in vivo active loading recovers cartilage strain, and possibly hydration, opens new opportunities for understanding the long term biomechanical and cellular responses to active loading.




Acknowledgements (Optional): : This work was supported by NIH COBRE 2P20GM 103653-06.

References (Optional): :
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[4] S. Uzuner et al, J. Mech. Behav. Biomed. Mater. (2021).




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[6] C.S. Paranjape et al, Sci. Rep. (2019).




[7] W. Wirth et al, Osteoarthr. Cartil. (2022).




[8] K.A. Taylor et al, J. Biomech. (2018).