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Orthopedic and Rehabilitation Engineering

Orthopedic and Rehabilitation Engineering - Poster Session E

Poster AA6 - Reduced Tendon Biomechanics in Regenerative Spiny Mice: A Comparative Study with CD1 Mice

Saturday, October 26, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Spiny mice (Genus: Acomys) are the only known mammalian adult with remarkable regenerative abilities as demonstrated by scar-free healing of dermal wounds and skeletal muscle. While insights on Acomys regeneration comes from skin and muscle, other musculoskeletal tissues such as tendons and ligaments have not been studied to date. Mammalian tendons are hypocellular and hypovascular predisposing the damaged/injured tissues to impaired regeneration. If Acomys tendons follow the same trend as skin and muscle, enhanced repair mechanisms can inspire clinical therapeutic strategies to improve patient outcomes. Here, we investigated the mechanical and structural properties of Acomys Achilles’ tendon and compared with regular laboratory mice (CD1 strain), a non-regenerative counterpart, that heals by forming a scar.

Materials and

Methods:  Spiny mice (Acomys) Achilles tendons (n = 10, 6 males and 4 females) were harvested from both hindlimbs and prepared for uniaxial, tensile testing in a bioreactor. CD1 mice (n = 5, 2 males and 3 females) were utilized as controls. The tendons were measured for cross sectional area and length before sandwiching the ends between sandpaper and loading into a bioreactor. Wells were filled with 1x Phosphate Buffer Solution (PBS) until tendons were submerged and loading commenced at room temperature. The tendons underwent a preconditioning loading protocol before ramping to failure at a rate of 0.3% strain / second. The data was collected and analyzed to determine ultimate tensile stress (UTS) and Young’s modulus (E). Values that were two standard deviations outside of the respective mean were considered outliers and sequentially removed from the data sets. Students’ t-test, One-way and Two-way ANOVA (Fishers) statistical analyses were conducted in GraphPad Prism. Statistical comparisons were made between species type, right and left limbs, and sexes.

Results, Conclusions, and Discussions: This study aimed to investigate the mechanical properties of the spiny mice Achilles' tendons relative to CD1 mice. Our findings reveal significant differences in mechanics between the two species, with spiny mice exhibiting inferior mechanics relative to CD1 mice (Figure 1). Specifically, the UTS and E of Spiny mice are significantly lower than CD1 mice. To establish consistency in mechanical testing, we compared the UTS and E of left and right Achilles' tendons in both CD1 mice and spiny mice (Figure 2). No significant differences were observed between the left and right tendons for either group. To investigate potential sex differences in tendon mechanics, we compared the UTS and E of Achilles' tendons in male and spiny mice and male and CD1 mice (Figure 3). This analysis revealed significant differences only between female spiny mice, with female CD1 tendons generally exhibiting greater tensile strength and stiffness compared to female spiny mice.
This is the first study to characterize spiny mouse Achilles tendon mechanics. Initial results confirm trends observed in skeletal muscle and skin, which remain to be confirmed in the Achilles tendon. The average E for CD1 mice is higher than previously observed values, with a notably high standard deviation across groups, suggesting potential measurement errors. However, similar observations in other tissues support the validity of our results. Sex differences in tendon properties show structural and mechanical variations influenced by hormones, such as estrogen. Our results interestingly reveal that only female spiny mice have significantly lower mechanics compared to female CD1 mice, possibly highlighting differences in estrogen effects across species and their impact on tendon mechanics. Increasing the sample size in future studies will help clarify these findings.
Future work will involve isolating primary Achilles tenocyte cells, establishing compositional and structural differences between spiny mice and CD1 mice extracellular matrix, and evaluating tendinous healing responses.

Acknowledgements (Optional):