Structure and Function Are Not the Same: The Case for Restoring Mechanoreceptor Continuity Following Anterior Cruciate Ligament Injury.

Anterior cruciate ligament (ACL) injury, particularly in increasingly young and active adolescents, continues to pose a clinical challenge with re-injury rates reported as high as 30%. Evidence also suggests that current standard-of-care ACL reconstruction (ACLR) does not mitigate post-traumatic osteoarthritis (PTOA) risk. Bridge- enhanced ACL restoration (BEAR) is a recently developed and tested ACL surgery that promotes primary healing of the native ACL with excellent early results. BEAR has shown to reduce signs of early PTOA compared to ACLR in an animal model. Here, we describe a theoretical framework related to re-innervation that can clarify why the outcomes of ACLR and BEAR surgeries differ. We also discuss how ongoing and new challenges in determining return-to-sport readiness following the competing surgeries may differ, and how emerging imaging tools and measures of neuromuscular function may aid in clinical decision-making to decrease the likelihood of re-injury and PTOA risk.

Assessment of ultrashort echo time (UTE) T2* mapping at 3T for the whole knee: repeatability, the effects of fat suppression, and knee position.

Background: Knee tissues such as tendon, ligament and meniscus have short T2* relaxation times and tend to show little to no signal in conventional magnetic resonance acquisitions. An ultrashort echo time (UTE) technique offers a unique tool to probe fast-decaying signals in these tissues. Clinically relevant factors should be evaluated to quantify the sensitivity needed to distinguish diseased from control tissues. Therefore, the objectives of this study were to (I) quantify the repeatability of UTE-T2* relaxation time values, and (II) evaluate the effects of fat suppression and (III) knee positioning on UTE-T2* relaxation time quantification. Methods: A dual-echo, three-dimensional center-out radially sampling UTE and conventional gradient echo sequences were utilized to image gadolinium phantoms, one ex-vivo specimen, and five in-vivo subjects on a clinical 3T scanner. Scan-rescan images from the phantom and in-vivo experiments were used to evaluate the repeatability of T2* relaxation time values. Fat suppressed and non-suppressed images were acquired for phantoms and the ex-vivo specimen to evaluate the effect of fat suppression on T2* relaxation time quantifications. The effect of knee positioning was evaluated by imaging in-vivo subjects in extended and flexed positions within the knee coil and comparing T2* relaxation times quantified from tissues in each position. Results: Phantom and in-vivo measurements demonstrated repeatable T2* mapping, where the percent difference between T2* relaxation time quantified from scan-rescan images was less than 8% for the phantom and knee tissues. The coefficient of variation across fat suppressed and non-suppressed images was less than 5% for the phantoms and ex-vivo knee tissues, showing that fat suppression had a minimal effect on T2* relaxation time quantification. Knee position introduced variability to T2* quantification of the anterior cruciate ligament, posterior cruciate ligament, and patellar tendon, with percent differences exceeding 20%, but the meniscus showed a percent difference less than 10%. Conclusions: The 3D radial UTE sequence presented in this study could potentially be used to detect clinically relevant changes in mean T2* relaxation time, however, reproducibility of these values is impacted by knee position consistency between scans.

A novel large animal model of posttraumatic osteoarthritis induced by inflammation with mechanical stability.

OBJECTIVES: Animal models are needed to reliably separate the effects of mechanical joint instability and inflammation on posttraumatic osteoarthritis (PTOA) pathogenesis. We hypothesized that our modified intra-articular drilling (mIAD) procedure induces cartilage damage and synovial changes through increased inflammation without causing changes in gait. METHODS: Twenty-four Yucatan minipigs were randomized into the mIAD (n=12) or sham control group (n=12). mIAD animals had two osseous tunnels drilled into each of the tibia and femur adjacent to the anterior cruciate ligament (ACL) attachment sites on the left hind knee. Surgical and contralateral limbs were harvested 15 weeks post-surgery. Cartilage degeneration was evaluated macroscopically and histologically. Synovial changes were evaluated histologically. Interleukin-1 beta (IL-1ß), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) mRNA expression levels in the synovial membrane were measured using quantitative real-time polymerase chain reaction. IL-1ß and NF-κB levels in chondrocytes were assessed using immunohistochemistry. Load asymmetry during gait was recorded by a pressure-sensing walkway system before and after surgery. RESULTS: The mIAD surgical knees demonstrated greater gross and histological cartilage damage than contralateral (P<.01) and sham knees (P<.05). Synovitis was present only in the mIAD surgical knee. Synovial inflammatory marker (IL-1ß, NF-κB, and TNF-α) expression was three times higher in the mIAD surgical knee than the contralateral (P<.05). Chondrocyte IL-1ß and NF-κB levels were highest in the mIAD surgical knee. In general, there were no significant changes in gait. CONCLUSIONS: The mIAD model induced PTOA through inflammation without affecting gait mechanics. This large animal model has significant applications for evaluating the role of inflammation in PTOA and for developing therapies aimed at reducing inflammation following joint injury.

Long-Term Bilateral Neuromuscular Function and Knee Osteoarthritis after Anterior Cruciate Ligament Reconstruction.

Neuromuscular function is thought to contribute to posttraumatic osteoarthritis (PTOA) risk in anterior cruciate ligament (ACL)-reconstructed (ACLR) patients, but sensitive and easy-to-use tools are needed to discern whether complex muscle activation strategies are beneficial or maladaptive. Using an electromyography (EMG) signal analysis technique coupled with a machine learning approach, we sought to: (1) identify whether ACLR muscle activity patterns differed from those of healthy controls, and (2) explore which combination of patient outcome measures (thigh muscle girth, knee laxity, hop distance, and activity level) predicted the extent of osteoarthritic changes via magnetic resonance imaging (MRI) in ACLR patients. Eleven ACLR patients 10-15 years post-surgery and 12 healthy controls performed a hop activity while lower limb muscle EMG was recorded bilaterally. Osteoarthritis was evaluated based on MRI. ACLR muscle activity patterns were bilaterally symmetrical and differed from those of healthy controls, suggesting the presence of a global adaptation strategy. Smaller ipsilateral thigh muscle girth was the strongest predictor of inferior MRI scores. The ability of our EMG analysis approach to detect meaningful neuromuscular differences that could ultimately be related to thigh muscle girth provides the foundation to further investigate a direct link between muscle activation patterns and PTOA risk.

Predicting anterior cruciate ligament failure load with T2* relaxometry and machine learning as a prospective imaging biomarker for revision surgery.

Non-invasive methods to document healing anterior cruciate ligament (ACL) structural properties could potentially identify patients at risk for revision surgery. The objective was to evaluate machine learning models to predict ACL failure load from magnetic resonance images (MRI) and to determine if those predictions were related to revision surgery incidence. It was hypothesized that the optimal model would demonstrate a lower mean absolute error (MAE) than the benchmark linear regression model, and that patients with a lower estimated failure load would have higher revision incidence 2 years post-surgery. Support vector machine, random forest, AdaBoost, XGBoost, and linear regression models were trained using MRI T2* relaxometry and ACL tensile testing data from minipigs (n = 65). The lowest MAE model was used to estimate ACL failure load for surgical patients at 9 months post-surgery (n = 46) and dichotomized into low and high score groups via Youden's J statistic to compare revision incidence. Significance was set at alpha = 0.05. The random forest model decreased the failure load MAE by 55% (Wilcoxon signed-rank test: p = 0.01) versus the benchmark. The low score group had a higher revision incidence (21% vs. 5%; Chi-square test: p = 0.09). ACL structural property estimates via MRI may provide a biomarker for clinical decision making.

Wavelet analysis reveals differential lower limb muscle activity patterns long after anterior cruciate ligament reconstruction.

The purpose of this study was to test whether differences in muscle activity patterns between anterior cruciate ligament-reconstructed patients (ACLR) and healthy controls could be detected 10 to 15 years post-surgery using a machine learning classification approach. Eleven ACLR subjects and 12 healthy controls were recruited from an ongoing prospective randomized clinical trial. Surface electromyography (EMG) signals were recorded from gastrocnemius medialis and lateralis, tibialis anterior, vastus medialis, rectus femoris, biceps femoris, and semitendinosus muscles. Muscle activity was analyzed using wavelet analysis and examined within four sub-phases of the hop test, as well as an average of the task as a whole. K-nearest neighbor machine learning combined with a leave-one-out validation was used to classify the muscle activity patterns as either ACLR or Control. When muscle activity was averaged across the whole hop task, activity patterns for all muscles except the tibialis anterior were identified as being different between the study cohorts. ACLR patients demonstrated continuous muscle activities that spanned take-off, airborne, and landing hop phases versus healthy controls who displayed timed and regulated islets of muscle activities specific to each hop phase. The most striking features were 25-50% greater relative quadriceps intensity and approximately 66% diminished biceps femoris intensity in ACLR patients. The current findings are in contrast to previous work using conventional co-contraction and muscle activation onset EMG measures of the same dataset, underscoring the sensitivity and potential of the wavelet approach coupled with machine learning to reveal meaningful adaptation strategies in this at-risk population.

A transfer learning approach for automatic segmentation of the surgically treated anterior cruciate ligament.

Quantitative magnetic resonance imaging enables quantitative assessment of the healing anterior cruciate ligament or graft post-surgery, but its use is constrained by the need for time consuming manual image segmentation. The goal of this study was to validate a deep learning model for automatic segmentation of repaired and reconstructed anterior cruciate ligaments. We hypothesized that (1) a deep learning model would segment repaired ligaments and grafts with comparable anatomical similarity to intact ligaments, and (2) automatically derived quantitative features (i.e., signal intensity and volume) would not be significantly different from those obtained by manual segmentation. Constructive Interference in Steady State sequences were acquired of ACL repairs (n = 238) and grafts (n = 120). A previously validated model for intact ACLs was retrained on both surgical groups using transfer learning. Anatomical performance was measured with Dice coefficient, sensitivity, and precision. Quantitative features were compared to ground truth manual segmentation. Automatic segmentation of both surgical groups resulted in decreased anatomical performance compared to intact ACL automatic segmentation (repairs/grafts: Dice coefficient = .80/.78, precision = .79/.78, sensitivity = .82/.80), but neither decrease was statistically significant (Kruskal-Wallis: Dice coefficient p = .02, precision p = .09, sensitivity p = .17; Dunn post-hoc test for Dice coefficient: repairs/grafts p = .054/.051). There were no significant differences in quantitative features between the ground truth and automatic segmentation of repairs/grafts (0.82/2.7% signal intensity difference, p = .57/.26; 1.7/2.7% volume difference, p = .68/.72). The anatomical similarity performance and statistical similarities of quantitative features supports the use of this automated segmentation model in quantitative magnetic resonance imaging pipelines, which will accelerate research and provide a step towards clinical applicability.

Neuromuscular function in anterior cruciate ligament reconstructed patients at long-term follow-up.

BACKGROUND: The permanence of neuromuscular adaptations following anterior cruciate ligament reconstruction is not known. The aim of this study was to compare bilateral muscle co-contraction indices, time to peak ground reaction force, and timing of muscle onset between anterior cruciate ligament reconstruction subjects 10-15 years post reconstruction with those of matched uninjured controls during a one-leg hop landing. METHODS: Nine healthy controls and 9 reconstruction subjects were recruited. Clinical and functional knee exams were administered. Lower limb co-contraction indices, time to peak ground reaction force, and muscle onset times were measured bilaterally. Differences in clinical and functional outcomes were assessed with unpaired t-tests, and mixed model repeated measures were used to examine effects of group, limb and interaction terms in electromyography measures. FINDINGS: 89% of control knees were clinically "normal", whereas only 33% of reconstructed knees were "normal". Anterior cruciate ligament-reconstructed subjects tended to achieve shorter functional hop distances but demonstrated symmetrical lower limb electromyography measures that were no different from those of controls' with the exception that biceps femoris activation was delayed bilaterally prior to ground contact but was greater during the injury risk phase of landing. INTERPRETATION: With the exception of hamstring activation, lower limb electromyography measures were largely similar between ligament-reconstructed and matched control subjects, which was in contrast to the clinical findings. This result brings into question the significance of neuromuscular function at this long-term follow-up but raises new questions regarding the role of symmetry and pre-injury risk.

Cartilage Damage Is Related to ACL Stiffness in a Porcine Model of ACL Repair.

Inferior anterior cruciate ligament (ACL) structural properties may inadequately restrain tibiofemoral joint motion following surgery, contributing to the increased risk of post-traumatic osteoarthritis. Using both a direct measure of ACL linear stiffness and an in vivo magnetic resonance imaging (MRI) T2 *-based prediction model, we hypothesized that cartilage damage and ACL stiffness would increase over time, and that an inverse relationship between cartilage damage and ACL stiffness would emerge at a later stage of healing. After either 6, 12, or 24 weeks (w) of healing after ACL repair, ACL linear stiffness was determined from the force-displacement relationship during tensile testing ex vivo and predicted in vivo from the MRI T2 *-based multiple linear regression model in 24 Yucatan minipigs. Tibiofemoral cartilage was graded postmortem. There was no relationship between cartilage damage and ACL stiffness at 6 w (R2 = 0.04; p = 0.65), 12 w (R2 = 0.02; p = 0.77), or when the data from all animals were pooled (R2 = 0.02; p = 0.47). A significant inverse relationship between cartilage damage and ACL stiffness based on both ex vivo measurement (R2 = 0.90; p < 0.001) and in vivo MRI prediction (R2 = 0.78; p = 0.004) of ACL stiffness emerged at 24 w. This result suggests that 90% of the variability in gross cartilage changes is associated with the repaired ACL linear stiffness at 6 months of healing. Clinical Significance: Techniques that provide a higher stiffness to the repaired ACL may be required to mitigate the post-traumatic osteoarthritis commonly seen after ACL injury, and MRI T2 * can be used as a noninvasive estimation of ligament stiffness. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2249-2257, 2019.

Alterations in Joint Angular Velocity Following Traumatic Knee Injury in Ovine Models.

Little effort has been directed towards the consequence of an injury on joint angular velocity. We hypothesized that the magnitude of knee joint angular velocity would be decreased after injury. Four injury groups were investigated in an ovine model: (1) anterior cruciate ligament (ACL) and medial collateral ligament (MCL) transection (ACL/MCL Tx) (n = 5), (2) lateral meniscectomy (Mx) (n = 5), (3) partial ACL transection (p-ACL Tx) (n = 5), and (4) partial-ACL and MCL transection (p-ACL/MCL Tx) (n = 5). The magnitude of the angular velocities decreased in the subjects of all groups at multiple points of the gait cycle. The maximum angular velocities during stance and the maximum extension angular velocities during swing were decreased in 15/20 and 17/20 subjects, respectively. There were strong correlations between morphological osteoarthritis scores and the reduction in the maximum extension angular velocities during swing 40 weeks post-p-ACL Tx and 20 weeks post-ACL/MCL Tx. There was no correlation between the decrease of the angular velocity and morphological osteoarthritis scores in the Mx group and the p-ACL/MCL Tx group. The reduction in angular velocity may be a helpful addition as a surrogate measure of OA risk after ACL injury, and could have clinical significance after further investigation in humans.

Correlation between translational and rotational kinematic abnormalities and osteoarthritis-like damage in two in vivo sheep injury models.

The relations between kinematic abnormalities and post traumatic osteoarthritis have not yet been clearly elucidated. This study was conducted to determine the finite helical axes parameters and the tibiofemoral translation vector in the knee joints of two surgically induced injury sheep models: anterior cruciate ligament and medial collateral ligament transection (ACL/MCL Tx) (n = 5) and lateral meniscectomy (n = 5). We hypothesized that morphological damage in the experimental joints would be correlated to alterations in these kinematic variables. There was no strong evidence that morphological damage to the joints 20 weeks post ACL/MCL transection or meniscectomy was correlated with alterations in the finite helical axes variables. Nevertheless, significant correlations were found between the morphological damage to the joints and the magnitude of the change in the translation vectors after ACL/MCL transection (significant correlations (p = 0.005) during stance and trends (p < 0.1) at all points analyzed during swing). It can be concluded that: (1) osteoarthritic-like morphological damage after ACL/MCL transection is more critically correlated to the absolute tibiofemoral translational change and (2) alterations in analyzed kinematic variables cannot solely define osteoarthritis risk after meniscal injuries. From a clinical perspective, our results suggest that the magnitude of the change in the translation vector, which is independent of the coordinate system and combines the effects of the three translational degrees of freedom, i.e. medial-lateral, anterior-posterior and inferior-superior, would be an osteoarthritis risk factor after ligament injury, and requires validation in humans.

Magnetic resonance measurements of tissue quantity and quality using T2 * relaxometry predict temporal changes in the biomechanical properties of the healing ACL.

The purpose of this study was to develop a magnetic resonance T2 * relaxometry-based multiple linear regression model to predict the structural properties of the healing anterior cruciate ligament (ACL) over a 24-week healing period following ACL repair in Yucatan minipigs. Two hypotheses were tested: (i) that a regression model based on ACL sub-volumes containing short and long T2 * relaxation times would outperform a competing model based on sub-volumes of short T2 * relaxation times only; and (ii) that an optimized regression model would be capable of predicting ACL structural properties between 6 and 24 weeks post-repair. ACLs were imaged in 24 minipigs (8/group) at either 6, 12, or 24 weeks after ACL repair. The structural properties of the ACLs were determined from tensile failure tests. Four multiple linear regression models of increasing complexity were fitted to the data. Akaike Information Criterion values and Bland-Altman tests were used to compare model performance and to test the hypotheses. The structural properties predicted from the multiple linear regression model that was based on the change in ACL sub-volumes of both the short and long T2 * relaxation times over the healing period were in closest agreement to the measured values, suggesting that the amounts of both organized and disorganized collagen, and the change in these quantities over time, are required to predict the structural properties of healing ACLs accurately. CLINICAL SIGNIFICANCE: our time-specific, T2 *-based regression model may allow us to estimate the structural properties of ACL repairs in vivo longitudinally. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1701-1709, 2018.

Sensitivity of ACL volume and T2∗ relaxation time to magnetic resonance imaging scan conditions.

Anterior cruciate ligament (ACL) volume and T2∗ relaxation times from magnetic resonance (MR) images have been previously shown to predict the structural properties of healing ligaments. We investigated whether MR imaging scan resolution and condition (in vivo, in situ, or ex vivo) affected ACL volume and T2∗ relaxation times in intact ligaments. ACLs of 14 pigs were imaged using a 3T scanner and a six-channel flexcoil using at least two of four possible scan conditions: (1) in vivo moderate resolution (n=14); (2) in vivo high resolution (n=7); (3) in situ high resolution acquired within 60 minutes of euthanasia (n=6); and (4) ex vivo high resolution following hind limb disarticulation and one freeze-thaw cycle (n=7). T2∗ relaxation times were mapped to the ACL voxels. The total ACL volume was then divided into four sub-volumes (Vol1-4) based on predetermined increasing ranges of T2∗ times. ACL T2∗ statistics (first quartile, median, and standard deviation (SD)) were computed. Scan resolution had no effect on the total ACL volume, but Vol1 and first quartile T2∗ times decreased with high resolution and in situ/ex vivo scan conditions. The most dramatic differences in T2∗ summary statistics were between in vivo moderate and ex vivo high resolution scan conditions that included a freeze-thaw cycle: ACL T2∗ SD increased by over 50% in 9 animals, and more than 90% in 4 animals. Our results indicated that T2∗-based prediction models to quantify in vivo structural properties of healing ligaments should be based on high resolution in vivo MR scan conditions.

Relationship between increased in vivo meniscal loads and abnormal tibiofemoral surface alignment in ACL deficient sheep is varied.

The aim of this study was to quantify how abnormal dynamic tibiofemoral surface alignment affects the load bearing function of menisci in vivo. Using a sheep model of ACL deficiency, we tested the hypothesis that increased in vivo meniscal loads correlate with greater tibiofemoral surface alignment abnormality. Stifle kinematics were recorded using a bone-mounted instrumented spatial linkage in four sheep before, and at four and twenty weeks (w) after ACL transection. A parallel robotic manipulator was used to quantify stifle kinetics by reproducing each animal׳s in vivo kinematics and measuring tissue loads during gait. Meniscal resultant loads were estimated from the change in joint reaction force after sequentially removing load-bearing tissues. Tibiofemoral subchondral surfaces were then traced and modeled using thin plate splines. Proximity disturbance is a surface interaction measure used to quantify dynamic tibiofemoral surface alignment abnormality. ACL transection increased meniscal loads by 30-145% at 20w post-ACL transection, whereas the degree of dynamic tibiofemoral subchondral surface alignment varied between sheep. Positive and significant correlations between increased meniscal loads and proximity disturbance values >10mm were observed (R2=0.04-0.57; p≤0.05). Our results suggest that the proximity disturbance measure reflects abnormal meniscal loads following ACL injury; however given the range of R2 values, perturbations in dynamic tibiofemoral subchondral surface alignment do not explain abnormal joint kinetics entirely, and point to the presence of other dynamic compensatory mechanisms that may have a significant bearing on in vivo joint function and long-term joint health.

Rigorous geometric self-calibrating bundle adjustment for a dual fluoroscopic imaging system.

High-speed dual fluoroscopy is a noninvasive imaging technology for three-dimensional skeletal kinematics analysis that finds numerous biomechanical applications. Accurate reconstruction of bone translations and rotations from dual-fluoroscopic data requires accurate calibration of the imaging geometry and the many imaging distortions that corrupt the data. Direct linear transformation methods are commonly applied for performing calibration using a two-step process that suffers from a number of potential shortcomings including that each X-ray source and corresponding camera must be calibrated separately. Consequently, the true imaging set-up and the constraints it presents are not incorporated during calibration. A method to overcome such drawbacks is the single-step self-calibrating bundle adjustment method. This procedure, based on the collinearity principle augmented with imaging distortion models and geometric constraints, has been developed and is reported herein. Its efficacy is shown with a carefully controlled experiment comprising 300 image pairs with 48 507 image points. Application of all geometric constraints and a 31 parameter distortion model resulted in up to 91% improvement in terms of precision (model fit) and up to 71% improvement in terms of 3-D point reconstruction accuracy (0.3-0.4 mm). The accuracy of distance reconstruction was improved from 0.3±2.0 mm to 0.2 ±1.1 mm and angle reconstruction accuracy was improved from -0.03±0.55(°) to 0.01±0.06(°). Such positioning accuracy will allow for the accurate quantification of in vivo arthrokinematics crucial for skeletal biomechanics investigations.

A new measure of tibiofemoral subchondral bone interactions that correlates with early cartilage damage in injured sheep.

We have demonstrated previously that chondral damage is associated with increased knee surface velocities following ligament and meniscus injuries in sheep. We tested the hypothesis that cartilage damage scores would correlate with a new bone surface interaction measure that captures complex changes in tibiofemoral alignment, "proximity disturbance" (PD). Six sheep underwent combined anterior cruciate and medial collateral ligament transection (ACL/MCLx), five complete lateral meniscectomy (Mx), and four sham arthrotomy (Sham). Tibiofemoral subchondral bone surfaces were modeled, and the post-operative changes in relative separation of the surfaces (i.e., "proximity") were derived from subject-specific in vivo 3D stifle kinematics. Surface areas of regions of near contact were determined, and PD was calculated as the range of change in tibiofemoral proximity, divided by normalized overlapping proximity surface areas between baseline and post-operative time points. Cartilage morphology was graded at dissection. ACL/MCLx PD was significantly elevated relative to Mx and Shams, and correlated with cartilage damage (r(2) = 0.88-0.98). Although not statistically significant, Mx PD values tended to be higher than those of Shams, and correlated with cartilage damage. Results from both injury models suggest that increasing change in tibiofemoral surface alignment may be increasingly deleterious to long-term cartilage health in sheep.

Repeatability and precision of a weighted centroid method for estimating dynamic in vivo tibiofemoral surface interactions in sheep.

Persistent changes in joint biomechanics resulting from knee injury are thought to contribute to progressive cartilage damage and post-traumatic osteoarthritis (PTOA). The identification and quantification of in vivo tibiofemoral surface interactions are critical to understanding them, particularly abnormal interactions that are damaging to articular cartilage and other structures of the knee. In this study, we describe an approach for understanding such potential interactions by using a weighted centroid derived from in vivo stifle kinematics in sheep. Collectively, repeatability and sensitivity analyses indicate that the magnitude of the changes in tibiofemoral centroid location resulting from combined ligament transection is greater than the repeatability and precision of the current weighted centroid approach, making this method useful for describing the changes in dynamic surface interactions that may be relevant in the pathogenesis of PTOA in this stifle injury model.

Tibiofemoral centroid velocity correlates more consistently with cartilage damage than does contact path length in two ovine models of stifle injury.

Anterior cruciate ligament (ACL) rupture and/or meniscal injury are known risk factors for post-traumatic osteoarthritis. We tested the hypothesis that increasingly abnormal tibiofemoral centroid path lengths and velocities would correlate with the severity of cartilage damage in injured sheep. Six sheep underwent combined ACL/medial collateral ligament transection (ACL/MCLx), five complete lateral meniscectomy (Mx), and four sham arthrotomy (Sham). Weighted centroids were used to estimate in vivo tibiofemoral cartilage contact path length during stance and the velocity of relative motion. Cartilage morphology was graded at dissection. Ligament transection significantly elongated plateau centroid path lengths and velocities, whereas condyle paths and velocities were reduced. Differences between plateau and femoral velocities (relative centroid velocity) were increased up to 10-fold over baseline values in the medial compartment. Reductions in Mx lateral compartment paths were significantly different from ACL/MCLx paths, but not relative to baseline or Sham values. Importantly, only centroid velocities consistently correlated with cartilage damage in either injury model, suggesting that while path length is valuable in detecting changes in the envelope of joint motion, it may average out meaningful peaks in the rate of relative motion that more closely relate to the mechanisms that might be damaging articular cartilage in these models.

Osteoarthritis develops in the operated joint of an ovine model following ACL reconstruction with immediate anatomic reattachment of the native ACL.

We tested the hypothesis that immediate reattachment of the native anterior cruciate ligament (ACL) can prevent kinematic changes and the development of osteoarthritis (OA). Five sheep underwent anatomic unilateral ACL reconstruction (ACL-R). Animals from a previous study served as sham (n = 7) or non-operated (n = 17) controls. At 4 points of walking gait, 6 degrees of freedom stifle joint kinematics of ACL-R animals were compared with sham controls at 4 and 20 weeks post-surgery. Gross cartilage, bone, and meniscal changes were graded at euthanasia; paired and differential scores were compared. Inter-animal differences were noted in all groups. Of 48 points of gait comparison between ACL-R and sham operated groups, 42 points showed no difference (p > 0.05). Of the six significant differences (p < 0.05), internal rotation in ACL-R animals accounted for three. At 20 weeks, differential scores showed that sham operated joints were morphologically indistinguishable from non-operated controls (p ≥ 0.129) while ACL-R joints had significantly higher combined cartilage and osteophyte scores than those controls (p ≤ 0.003). This method of ACL reconstruction in sheep did not restore normal walking gait kinematics completely and allowed some OA to develop in operated joints. OA may result from relatively subtle mechanical abnormalities, apparently more so in some individuals than others.

Complete ACL/MCL deficiency induces variable degrees of instability in sheep with specific kinematic abnormalities correlating with degrees of early osteoarthritis.

People are not equally disabled by combined anterior cruciate ligament (ACL)/medial collateral ligament (MCL) injuries, nor do they all develop osteoarthritis (OA). Although biological/biomechanical causes are not clear, some association presumably exists between joint instability and OA development. We hypothesized that degree of OA development following standardized complete ACL/MCL injuries will vary directly with the degree of biomechanical abnormality between individuals. Three groups of sheep were used to test the hypothesis: 17 normal, 9 ACL/MCL transected, and 7 sham animals. Normal joints were assessed morphologically while sham and experimental animals had gait assessment pre- and at 4 and 20 weeks post-surgery, with cartilage and bone changes being mapped and graded at sacrifice at 20 weeks. Sham joints were morphologically normal and had only one minor kinematic change at 20 weeks. Although variable, ACL/MCL deficient animals showed significant kinematic abnormalities in 4/6 degrees of freedom (DOFs), as well as cartilage/bone damage by 20 weeks (p < 0.05). Linear regression analysis revealed that changes in medial-lateral (ML) translation were related to the current level of joint degradation as represented by total gross OA score (p = 0.0044, R(2) = 0.71) in the ACL/MCL transected group. Even identical ACL/MCL injuries result in inter-animal variations in instability and OA, however significant kinematic abnormalities in ML translation do relate to early OA in sheep.