Abstract
Knee meniscus injuries are the most frequent causes of orthopedic surgical procedures in the U.S., motivating tissue engineering attempts and the need for suitable animal models. Despite extensive use in cardiovascular research and the existence of characterization data for the menisci of farm pigs, the farm pig may not be a desirable preclinical model for the meniscus due to rapid weight gain. Minipigs are conducive to in vivo experiments due to their slower growth rate than farm pigs and similarity in weight to humans. However, characterization of minipig knee menisci is lacking. The objective of this study was to extensively characterize structural and functional properties within different regions of both medial and lateral Yucatan minipig knee menisci to inform this model’s suitability as a preclinical model for meniscal therapies. Menisci measured 23.2–24.8 mm in anteroposterior length (33–40 mm for human), 7.7–11.4 mm in width (8.3–14.8 mm for human), and 6.4–8.4 mm in peripheral height (5–7 mm for human). Per wet weight, biochemical evaluation revealed 23.9–31.3% collagen (COL; 22% for human) and 1.20–2.57% glycosaminoglycans (GAG; 0.8% for human). Also, per dry weight, pyridinoline crosslinks (PYR) were 0.12–0.16% (0.12% for human) and, when normalized to collagen content, reached as high as 1.45–1.96 ng/µg. Biomechanical testing revealed circumferential Young’s modulus of 78.4–116.2 MPa (100–300 MPa for human), circumferential ultimate tensile strength (UTS) of 18.2–25.9 MPa (12–18 MPa for human), radial Young’s modulus of 2.5–10.9 MPa (10–30 MPa for human), radial UTS of 2.5–4.2 MPa (1–4 MPa for human), aggregate modulus of 157–287 kPa (100–150 kPa for human), and shear modulus of 91–147 kPa (120 kPa for human). Anisotropy indices ranged from 11.2–49.4 and 6.3–11.2 for tensile stiffness and strength (approximately 10 for human), respectively. Regional differences in mechanical and biochemical properties within the minipig medial meniscus were observed; specifically, GAG, PYR, PYR/COL, radial stiffness, and Young’s modulus anisotropy varied by region. The posterior region of the medial meniscus exhibited the lowest radial stiffness, which is also seen in humans and corresponds to the most prevalent location for meniscal lesions. Overall, similarities between minipig and human menisci support the use of minipigs for meniscus translational research.
Highlights
Damage to the knee meniscus can result from trauma or agerelated degeneration; meniscal lesions are the most common intra-articular knee injury and account for the most frequent cause of orthopedic surgical procedures in the U.S (Salata et al, 2010)
The anterior and posterior regions of the lateral meniscus exhibited significantly higher peripheral heights when compared to the central region; there were no significant differences in peripheral heights among medial meniscus regions
The objective of this study was to characterize the knee menisci of Yucatan minipigs because the minipig has been proposed as a large animal model for translational cartilage and meniscus research
Summary
Damage to the knee meniscus can result from trauma or agerelated degeneration; meniscal lesions are the most common intra-articular knee injury and account for the most frequent cause of orthopedic surgical procedures in the U.S (Salata et al, 2010). Differences in injury prevalence between medial and lateral menisci can result from differences in structural properties and, functionality, making it important to consider these properties during every step of developing new therapies, such as tissue engineered menisci. Toward demonstrating efficacy of novel meniscal therapies, appropriate animal models will be needed to traverse the regulatory process. These animals should have menisci with morphological, biomechanical, and biochemical properties that are comparable to humans; similarities in gait, joint anatomy, and joint biomechanics should be considered to facilitate translation (Donahue et al, 2019)
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