Dataset Information

Orientation changes in the cruciate ligaments of the knee during skeletal growth: A porcine model.

ABSTRACT: Musculoskeletal injuries in pediatric patients are on the rise, including significant increases in anterior cruciate ligament (ACL) injuries. Previous studies have found major anatomical changes during skeletal growth in the soft tissues of the knee. Specifically, the ACL and the posterior cruciate ligament (PCL) change in their relative orientation to the tibial plateau throughout growth. In order to develop age-specific treatments for ACL injuries, the purpose of this study was to characterize orientation changes in the cruciate ligaments of the Yorkshire pig, a common pre-clinical model, during skeletal growth in order to verify the applicability of this model for pediatric musculoskeletal studies. Hind limbs were isolated from female Yorkshire pigs ranging in age from newborn to late adolescence and were then imaged using high field strength magnetic resonance imaging. Orientation changes were quantified from the magnetic resonance images using image segmentation software. Statistically significant increases were found in the coronal and sagittal angles of the ACL relative to the tibial plateau during pre-adolescent growth. Additional changes were observed in the PCL angle, Blumensaat angle, intercondylar roof angle, and the aspect ratio of the intercondylar notch. Only the sagittal angle of the ACL relative to the tibial plateau experienced statistically significant changes through late adolescence. The age-dependent properties of the ACL and PCL in the female pig mirrored results found in female human patients, suggesting that the porcine model may provide a pre-clinical platform to study the cruciate ligaments during skeletal growth. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2725-2732, 2017.

SUBMITTER: Cone SG

PROVIDER: S-EPMC5671372 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Orientation changes in the cruciate ligaments of the knee during skeletal growth: A porcine model.

Cone Stephanie G SG Simpson Sean G SG Piedrahita Jorge A JA Fordham Lynn A LA Spang Jeffrey T JT Fisher Matthew B MB

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20170523 12

Musculoskeletal injuries in pediatric patients are on the rise, including significant increases in anterior cruciate ligament (ACL) injuries. Previous studies have found major anatomical changes during skeletal growth in the soft tissues of the knee. Specifically, the ACL and the posterior cruciate ligament (PCL) change in their relative orientation to the tibial plateau throughout growth. In order to develop age-specific treatments for ACL injuries, the purpose of this study was to characterize ...[more]

PMID: 28471537

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Project description:This review describes a novel method developed for processing porcine tendon and other ligament implants that enables in situ remodeling into autologous ligaments in humans. The method differs from methods using extracellular matrices (ECMs) that provide postoperative orthobiological support (i.e., augmentation grafts) for healing of injured ligaments, in that the porcine bone-patellar-tendon-bone itself serves as the graft replacing ruptured anterior cruciate ligament (ACL). The method allows for gradual remodeling of porcine tendon into autologous human ACL while maintaining the biomechanical integrity. The method was first evaluated in a preclinical model of monkeys and subsequently in patients. The method overcomes detrimental effects of the natural anti-Gal antibody and harnesses anti-non-gal antibodies for the remodeling process in two steps: Step 1. Elimination of ?-gal epitopes-this epitope that is abundant in pigs (as in other nonprimate mammals) binds the natural anti-Gal antibody, which is the most abundant natural antibody in humans. This interaction, which can induce fast resorption of the porcine implant, is avoided by enzymatic elimination of ?-gal epitopes from the implant with recombinant ?-galactosidase. Step 2. Partial cross-linking of porcine tendon with glutaraldehyde-this cross-linking generates covalent bonds in the ECM, which slow infiltration of macrophages into the implant. Anti-non-gal antibodies are produced in recipients against the multiple porcine antigenic proteins and proteoglycans because of sequence differences between human and porcine homologous proteins. Anti-non-gal antibodies bind to the implant ECM, recruit macrophages, and induce the implant destruction by directing proteolytic activity of macrophages. Partial cross-linking of the tendon ECM decreases the extent of macrophage infiltration and degradation of the implant and enables concomitant infiltration of fibroblasts that follow the infiltrating macrophages. These fibroblasts align with the implant collagen fibers and secrete their own collagen and other ECM proteins, which gradually remodel the porcine tendon into human ACL. This ligamentization process lasts ?2 years and the biomechanical integrity of the graft is maintained throughout the whole period. These studies are the first, and so far the only, to demonstrate remodeling of porcine tendon implants into permanently functional autologous ACL in humans.

Project description:BACKGROUND:Altered knee kinematics after anterior cruciate ligament injury and reconstruction (ACLR) have been implicated in the development of posttraumatic osteoarthritis (PTOA), leading to poor long-term clinical outcomes. PURPOSE:This study was conducted to determine (1) whether the average knee center of rotation (KCOR), a multidimensional metric of knee kinematics, of the ACL-reconstructed knee during walking differs from that of the uninjured contralateral knee; (2) whether KCOR changes between 2 and 4 years after surgery; and (3) whether early KCOR changes predict patient-reported outcomes 8 years after ACLR. STUDY DESIGN:Descriptive laboratory study. METHODS:Twenty-six human participants underwent gait analysis with calculation of bilateral KCOR during walking at 2 and 4 years after unilateral ACLR. Knee injury and Osteoarthritis Outcome Score (KOOS) and Lysholm score results were collected at 2, 4, and 8 years after ACLR in 13 of these participants. RESULTS:The ACL-reconstructed knee showed greater medial compartment motion because of pivoting about a more lateral KCOR ( P = .03) than the contralateral knee at 2 years. KCOR became less lateral over time ( P = .047), with values approaching those of the uninjured knee by 4 years ( P = .55). KCOR was also more anterior in the ACL-reconstructed knee at 2 years ( P = .02). Between 2 and 4 years, KCOR moved posteriorly in 16 (62%) and anteriorly in 10 (38%) participants. Increasing the anterior position of KCOR in the ACL-reconstructed knee from 2 to 4 years correlated with worsening clinical outcomes at 4 years (KOOS-Quality of Life, R2 = 0.172) and more strongly at 8 years (Lysholm score, R2 = 0.41; KOOS-Pain, R2 = 0.37; KOOS-Symptoms, R2 = 0.58; and KOOS-Quality of Life, R2 = 0.50). CONCLUSION:The observed changes to KCOR during walking between 2 and 4 years after ACLR show progressive improvement toward kinematic symmetry over the 2-year follow-up. The correlation between increasingly abnormal kinematics and worsening clinical outcomes years later in a subset of participants provides a potential explanation for the incidence of PTOA after ACLR.

Dataset Information

Orientation changes in the cruciate ligaments of the knee during skeletal growth: A porcine model.

Publications

Orientation changes in the cruciate ligaments of the knee during skeletal growth: A porcine model.

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