Background ACL injuries are becoming increasingly common in children and adolescents, but little is known regarding age-specific ACL function in these patients. To improve our understanding of changes in musculoskeletal tissues during growth and given the limited availability of pediatric human cadaveric specimens, tissue structure and function can be assessed in large animal models, such as the pig. Questions/purposes Using cadaveric porcine specimens ranging throughout skeletal growth, we aimed to assess age-dependent changes in (1) joint kinematics under applied AP loads and varus-valgus moments, (2) biomechanical function of the ACL under the same loads, (3) the relative biomechanical function of the anteromedial and posterolateral bundles of the ACL; and (4) size and orientation of the anteromedial and posterolateral bundles. Methods Stifle joints (analogous to the human knee) were collected from female Yorkshire crossbreed pigs at five ages ranging from early youth to late adolescence (1.5, 3, 4.5, 6, and 18 months; n = 6 pigs per age group, 30 total), and MRIs were performed. A robotic testing system was used to determine joint kinematics (AP tibial translation and varus-valgus rotation) and in situ forces in the ACL and its bundles in response to applied anterior tibial loads and varus-valgus moments. To see if morphological changes to the ACL compared with biomechanical changes, ACL and bundle cross-sectional area, length, and orientation were calculated from MR images. Results Joint kinematics decreased with increasing age. Normalized AP tibial translation decreased by 44% from 1.5 months (0.34 ± 0.08) to 18 months (0.19 ± 0.02) at 60° of flexion (p < 0.001) and varus-valgus rotation decreased from 25° ± 2° at 1.5 months to 6° ± 2° at 18 months (p < 0.001). The ACL provided the majority of the resistance to anterior tibial loading at all age groups (75% to 111% of the applied anterior force; p = 0.630 between ages). Anteromedial and posterolateral bundle function in response to anterior loading and varus torque were similar in pigs of young ages. During adolescence (4.5 to 18 months), the in situ force carried by the anteromedial bundle increased relative to that carried by the posterolateral bundle, shifting from 59% ± 22% at 4.5 months to 92% ± 12% at 18 months (data for 60° of flexion, p < 0.001 between 4.5 and 18 months). The cross-sectional area of the anteromedial bundle increased by 30 mm2 throughout growth from 1.5 months (5 ± 2 mm2) through 18 months (35 ± 8 mm2; p < 0.001 between 1.5 and 18 months), while the cross-sectional area of the posterolateral bundle increased by 12 mm2 from 1.5 months (7 ± 2 mm2) to 4.5 months (19 ± 5 mm2; p = 0.004 between 1.5 and 4.5 months), with no further growth (17 ± 7 mm2 at 18 months; p = 0.999 between 4.5 and 18 months). However, changes in length and orientation were similar between the bundles. Conclusion We showed that the stifle joint (knee equivalent) in the pig has greater translational and rotational laxity in early youth (1.5 to 3 months) compared with adolescence (4.5 to 18 months), that the ACL functions as a primary stabilizer throughout growth, and that the relative biomechanical function and size of the anteromedial and posterolateral bundles change differently with growth. Clinical Relevance Given the large effects observed here, the age- and bundle-specific function, size, and orientation of the ACL may need to be considered regarding surgical timing, graft selection, and graft placement. In addition, the findings of this study will be used to motivate pre-clinical studies on the impact of partial and complete ACL injuries during skeletal growth.

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Prior studies have analyzed growth of musculoskeletal tissues between species or across body segments; however, little research has assessed the differences in similar tissues within a single joint. Here we studied changes in the length and cross-sectional area of four ligaments and tendons, (anterior cruciate ligament, patellar tendon, medial collateral ligament, lateral collateral ligament) in the tibiofemoral joint of female Yorkshire pigs through high-field magnetic resonance imaging throughout growth. Tissue lengths increased by 4- to 5-fold from birth to late adolescence across the tissues while tissue cross-sectional area increased by 10–20-fold. The anterior cruciate ligament and lateral collateral ligament showed allometric growth favoring change in length over change in cross-sectional area while the patellar tendon and medial collateral ligament grow in an isometric manner. Additionally, changes in the length and cross-sectional area of the anterior cruciate ligament did not increase as much as in the other ligaments and tendon of interest. Overall, these findings suggest that musculoskeletal soft tissue morphometry can vary within tissues of similar structure and within a single joint during post-natal growth.

23Prior studies have analyzed growth of musculoskeletal tissues between species or 24 across body segments; however, little research has assessed the differences in similar 25 tissues within a single joint. Here we studied changes in the length and cross-sectional 26 area of four ligaments and tendons, (anterior cruciate ligament, patellar tendon, medial 27 collateral ligament, lateral collateral ligament) in the tibiofemoral joint of female 28Yorkshire pigs through high-field magnetic resonance imaging throughout growth. 29Tissue lengths increased by 4-to 5-fold from birth to late adolescence across the 30 tissues while tissue cross-sectional area increased by 10-20-fold. The anterior cruciate 31 ligament and lateral collateral ligament showed allometric growth favoring change in 32 length over change in cross-sectional area while the patellar tendon and medial 33 collateral ligament grow in an isometric manner. Additionally, changes in the length and 34 cross-sectional area of the anterior cruciate ligament did not increase as much as in the 35 other ligaments and tendon of interest. Overall, these findings suggest that 36 musculoskeletal soft tissue morphometry can vary within tissues of similar structure and 37 within a single joint during post-natal growth. 38 39 Joints within the musculoskeletal system consist of a complex combination of 41 active and passive tissues including ligaments and tendons that have specific 42 morphometric and mechanical properties enabling force generation and movement. 43Many studies have investigated early pre-natal development of ligaments and tendons 44(1-6). In addition, the structure, function, and biochemical makeup of ligaments and 45 tendons undergo major changes throughout both pre-natal and post-natal growth (7-11). 46Specific changes include increasing macroscale size and mechanical stiffness and 47 to the tibial insertion site (17). Interestingly, differences in growth rate coefficients were 63 found between the proximal bones of the hindlimb (femur) and forelimb (humerus) in the 64 porcine model through 3 months of age but not between the distal bones of the same 65 limbs (tibia and radius) (18). The same study found that both the tibia and femur 66 experienced more rapid change in bone area relative to bone length (allometric growth), 67 although the same trend was not found in the humerus (18). A study in human growth 68 insertion of the PT, and some insertion sites extended beyond the field of view of the 131 MRI scans for larger specimens. As such, the location of these insertion sites were 132 measured at the edge of the insertion most proximal to the joint center since this 133 landmark could be consistently identified in all specimens. The insertion was 134 determined as the centroid of points collected around the tissue at this location along 135 the tissue length. Furthermore, to avoid variability caused by the changing CSA near 136 the bony insertions, our CSA analysis was restricted to the midsubstance of the tissues. 137Specifically, the CSA was measured...