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The current study looks to: (i) investigate postural stability following anterior cruciate ligament (ACL) reconstruction, as assessed by Y-Balance Test, by comparing single-leg balance of the injured limb against those of controls and the uninjured limb; (ii) analyze the relationship between postural stability symmetry with localized cartilage matrix changes and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Bilateral knee MRI of 36 patients who underwent ACL reconstruction were performed before surgery, 6 months, 1 year, and 2 years, postoperatively. Postural stability was evaluated based on Y-Balance Test at 1 and 2 years. ACL patients were also split into three groups based on postural stability symmetry at 2 years and symmetry thresholds associated with elevated risks of lower extremity injury. Voxel-based relaxometry employing analysis of covariance was used to analyze localized differences in cartilage composition at all time-points (using quantitative magnetic resonance [MR] T1ρ and T2 mapping) between the three groups. The ACL patients displayed no significant deficits in postural stability. Compared with symmetric patients, those with asymmetric postural stability at 2 years had significantly prolonged cartilage T1ρ-indicating deterioration of the cartilage matrix-specifically in the injured knee's medial tibia as early as 6-month post-reconstruction. Prolonged T1ρ in asymmetric patients persisted up to 2 years, where the group also reported worse KOOS. Our results demonstrate an association between early stages of cartilage matrix deterioration and postural stability symmetry that may manifest in elevated lower extremity injury risk and worse patient-reported outcomes. Quantitative MR, in combination with local analysis performed with voxel-based relaxometry, is a tool to further study this relationship. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1132-1140, 2020., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Medial unicompartmental knee arthroplasty (UKA) is an accepted treatment for isolated medial osteoarthritis. However, using an improper thickness for the tibial component may contribute to early failure of the prosthesis or disease progression in the unreplaced lateral compartment. Little is known of the effect of insert thickness on both knee kinematics and ligament forces. Therefore, a computational model of the tibiofemoral joint was used to determine how non-conforming, fixed bearing medial UKA affects tibiofemoral kinematics, and tension in the medial collateral ligament (MCL) and the anterior cruciate ligament (ACL) during passive knee flexion. Fixed bearing medial UKA could not maintain the medial pivoting that occurred in the intact knee from 0° to 30° of passive flexion. Abnormal anterior-posterior (AP) translations of the femoral condyles relative to the tibia delayed coupled internal tibial rotation, which occurred in the intact knee from 0° to 30° of flexion, but occurred from 30° to 90° of flexion following UKA. Increasing or decreasing tibial insert thickness following medial UKA also failed to restore the medial pivoting behavior of the intact knee despite modulating MCL and ACL forces. Reduced AP constraint in non-conforming medial UKA relative to the intact knee leads to abnormal condylar translations regardless of insert thickness even with intact cruciate and collateral ligaments. This finding suggests that the conformity of the medial compartment as driven by the medial meniscus and articular morphology plays an important role in controlling AP condylar translations in the intact tibiofemoral joint during passive flexion. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1868-1875, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The purpose of this study was to develop a magnetic resonance T 2 * 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 T 2 * relaxation times would outperform a competing model based on sub-volumes of short T 2 * 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 T 2 * 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, T 2 *-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., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

This study determined how anterior cruciate ligament (ACL) reconstruction affected the magnitude and temporal patterns of anterior knee force and internal knee moment during 2000 cycles of simulated gait. Porcine knees were tested using a six degree-of-freedom robot, examining three porcine allograft materials compared with the native ACL. Reconstructions were performed using: (1) bone-patellar tendon-bone allograft (BPTB), (2) reconstructive porcine tissue matrix (RTM), or (3) an RTM-polymer hybrid construct (Hybrid). Forces and moments were measured over the entire gait cycle and contrasted at heel strike, mid stance, toe off, and peak flexion. The Hybrid construct performed the best, as magnitude and temporal changes in both anterior knee force and internal knee moment were not different from the native ACL knee. Conversely, the RTM knees showed greater loss in anterior knee force during 2000 cycles than the native ACL knee at heel strike and toe off, with an average force loss of 46%. BPTB knees performed the least favorably, with significant loss in anterior knee force at all key points and an average force loss of 61%. This is clinically relevant, as increases in post-operative knee laxity are believed to play a role in graft failure and early onset osteoarthritis., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

In this study, we explore topographical changes in proteoglycan distribution from femoral condylar cartilage in early osteoarthritis, acquired from both the lateral and medial condyles of anterior cruciate ligament transected (ACLT) and contralateral (CNTRL) rabbit knee joints, at 4 weeks post operation. Four sites across the cartilage surface in a parasagittal plane were defined across tissue sections taken from femoral condyles, and proteoglycan (PG) content was quantified using digital densitometry. The greatest depth-wise change in PG content due to an ACLT (compared to the CNTRL group) was observed anteriorly (site C) from the most weight-bearing location within the lateral compartment. In the medial compartment, the greatest change was observed in the most weight-bearing location (site B). The depth-wise changes in PG content were observed up to 48% and 28% depth from the tissue surface at these aforementioned sites, respectively (p < 0.05). The smallest depth-wise change in PG content was observed posteriorly (site A) from the most weight-bearing location within both femoral condyles (up to 20% and up to 5% depth from the tissue surface at lateral and medial compartments, respectively). This study gives further insight into how early cartilage deterioration progresses across the parasagittal plane of the femoral condyle., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

This study compared three-dimensional forces in knees containing anterior cruciate ligament (ACL) graft materials versus the native porcine ACL. A six-degree-of-freedom (DOF) robot simulated gait while recording the joint forces and moments. Knees were subjected to 10 cycles of simulated gait in intact, ACL-deficient, and ACL-reconstructed knee states to examine time zero biomechanical performance. Reconstruction was performed using bone-patellar tendon-bone allograft (BPTB), reconstructive porcine tissue matrix (RTM), and an RTM-polymer hybrid (Hybrid). Forces and moments were examined about anatomic DOFs throughout the gait cycle and at three key points during gait: heel strike (HS), mid stance (MS), toe off (TO). Compared to native ACL, each graft restored antero-posterior (A-P) forces throughout gait. However, all failed to mimic normal joint forces in other DOFs. For example, each reconstructed knee showed greater compressive forces at HS and TO compared to the native ACL knee. Overall, the Hybrid graft restored more of the native ACL forces following reconstruction than did BPTB, while RTM grafts were the least successful. If early onset osteoarthritis is in part caused by altered knee kinematics, then understanding how reconstruction materials restore critical force generation during gait is an essential step in improving a patient's long-term prognosis., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Administration of intra-articular medications, including corticosteroids and analgesics, is common clinical practice for knee pathology and dysfunction. Non-steroidal anti-inflammatory drugs (NSAIDs) are another category of medication commonly prescribed for their analgesic and anti-inflammatory properties. Recent studies demonstrated the efficacy of injectable NSAIDs in the treatment of intra-articular pathology and postoperative analgesia. However, little data exist regarding the safety of intra-articular injection, despite the increase in its application. Therefore, we investigated the effects of intra-articular NSAID injection on articular cartilage, the anterior cruciate ligament (ACL), and joint function in the rat. Sixty-four Sprague-Dawley rats were divided into either saline (SAL) or ketorolac (NSAID) tibiofemoral single injection treatment groups. Animals were euthanized at 2, 7, 28, and 84 days post-injection for histological and mechanical analyses. Additionally, a subset of animals underwent longitudinal ambulatory evaluation to determine joint functional properties. We hypothesized that intra-articular ketorolac injection would result in no detrimental mechanical, histological, or functional changes. No differences were reported between the NSAID and SAL groups in any of the parameters measured at any time point, demonstrating the potential safety of intra-articular NSAID administration. Therefore, NSAID injection could be further considered for clinical application in humans., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Our objective was to develop a non-invasive magnetic resonance (MR) method to predict the structural properties of a healing anterior cruciate ligament (ACL) using volume and T2 * relaxation time. We also compared our T2 *-based structural property prediction model to a previous model utilizing signal intensity, an acquisition-dependent variable. Surgical ACL transection followed by no treatment (i.e., natural healing) or bio-enhanced ACL repair was performed in a porcine model. After 52 weeks of healing, high-resolution MR images of the ACL tissue were collected. From these images, ligament volumes and T2 * maps were established. The structural properties of the ligaments were determined via tensile testing. Using the T2 * histogram profile, each ligament voxel was binned based on its T2 * value into four discrete tissue sub-volumes defined by specific T2 * intervals. The linear combination of the ligament sub-volumes binned by T2 * value significantly predicted maximum load, yield load, and linear stiffness (R(2)  = 0.92, 0.82, 0.88; p < 0.001) and were similar to the previous signal intensity based method. In conclusion, the T2 * technique offers a highly predictive methodology that is a first step towards the development of a method that can be used to assess ligament healing across scanners, studies, and institutions., (© 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Post-traumatic osteoarthritis (PTOA) is a common long-term consequence of joint injuries such as anterior cruciate ligament (ACL) rupture. In this study we used a tibial compression overload mouse model to compare knee injury induced at low speed (1 mm/s), which creates an avulsion fracture, to injury induced at high speed (500 mm/s), which induces midsubstance tear of the ACL. Mice were sacrificed at 0 days, 10 days, 12 weeks, or 16 weeks post-injury, and joints were analyzed with micro-computed tomography, whole joint histology, and biomechanical laxity testing. Knee injury with both injury modes caused considerable trabecular bone loss by 10 days post-injury, with the Low Speed Injury group (avulsion) exhibiting a greater amount of bone loss than the High Speed Injury group (midsubstance tear). Immediately after injury, both injury modes resulted in greater than twofold increases in total AP joint laxity relative to control knees. By 12 and 16 weeks post-injury, total AP laxity was restored to uninjured control values, possibly due to knee stabilization via osteophyte formation. This model presents an opportunity to explore fundamental questions regarding the role of bone turnover in PTOA, and the findings of this study support a biomechanical mechanism of osteophyte formation following injury., (© 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Articular loading is an important factor in the joint degenerative process for individuals with anterior cruciate ligament (ACL) rupture. Evaluation of loading for a population that exhibits neuromuscular compensation for injury requires an approach which can incorporate individual muscle activation strategies in its estimation of muscle forces. The purpose of this study was to evaluate knee joint contact forces for patients with ACL deficiency using an EMG-driven modeling approach to estimate muscle forces. Thirty athletes with acute, unilateral ACL rupture underwent gait analysis after resolving range of motion, effusion, pain, and obvious gait impairments. Electromyography was recorded bilaterally from 14 lower extremity muscles and input to a musculoskeletal model for estimation of muscle forces and joint contact forces. Gait mechanics were consistent with previous reports for individuals with ACL-deficiency. Our major finding was that joint loading was altered in the injured limb after acute ACL injury; patients walked with decreased contact force on their injured knee compared to their uninjured knee. Both medial and lateral compartment forces were reduced without a significant change in the distribution of tibiofemoral load between compartments. This is the first study to estimate medial and lateral compartment contact forces in patients with acute ACL rupture using an approach which is sensitive to individual muscle activation patterns. Further work is needed to determine whether this early decreased loading of the injured limb is involved in the development of osteoarthritis in these patients., (Copyright © 2012 Orthopaedic Research Society.)

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., (Copyright © 2012 Orthopaedic Research Society.)

Afferent proprioceptive information from the knee joint may be altered due to a reconstruction of the anterior cruciate ligament (ACL), which could result in changes of cortical activity. The aim of the study is to look if force sensation and cortical activation measured by EEG are influenced by an ACL-reconstruction when performing a force reproduction task. Nine patients after ACL reconstruction and nine healthy controls were asked to reproduce 50% of their maximal voluntary isometric contraction (MVIC) reproduction. EEG power values related to frequency bands and the error in reproduction were collected while performing the force reproduction. The aberration error demonstrated no significant differences between groups. The cortical activity results in significant higher frontal Theta power during the force reproduction task with the reconstructed limb (F3 and Fz: p < 0.05) of the ACL group compared to the controls. The EEG was able to measure changes in electrocortical activity after ACL-reconstruction in force reproduction, whereas performance data was not affected. The results were discussed in terms of differences in attentional control with involvement of the anterior cingulate cortex related to higher frontal Theta power in the ACL patients., (Copyright © 2011 Orthopaedic Research Society.)

This study sought to determine anterior force in the porcine knee during simulated 6-degree-of-freedom (DOF) motion to establish the role of the anterior cruciate ligament (ACL). Using a 6-DOF robot, a simulated ovine motion was applied to porcine hind limbs while recording the corresponding forces. Since the porcine knee is more lax than the ovine knee, anterior tibial translations were superimposed on the simulated motion in 2 mm increments from 0 mm to 10 mm to find a condition that would load the ACL. Increments through 8 mm increased anterior knee force, while the 10 mm increment decreased the force. Beyond 4 mm, anterior force increases were non-linear and less than the increases at 2 and 4 mm, which may indicate early structural damage. At 4 mm, the average anterior force was 76.9 ± 10.6 N (mean ± SEM; p < 0.025). The ACL was the primary restraint, accounting for 80-125% of anterior force throughout the range of motion. These results demonstrate the ACL dependence of the porcine knee for the simulated motion, suggesting this model as a candidate for studying ACL function. With reproducible testing conditions that challenge the ACL, this model could be used in developing and screening possible reconstruction strategies., (Copyright © 2010 Orthopaedic Research Society.)

Use of novel tissue engineering approaches to heal an injured anterior cruciate ligament (ACL) requires suture repair and/or augmentation to provide joint stability. We evaluated the effects of the location of suture augmentation at the femur and tibia in terms of joint stability using a goat model. Eight goat stifle joints were tested with augmentation sutures placed in two femoral tunnel locations: (1) anterior to, or (2) through the ACL footprint, and two tibial tunnel locations: (1) medial to, or (2) medial and lateral to the footprint. Using a robotic/universal force-moment sensor testing system, the anterior tibial translation (ATT) and the corresponding in situ force carried by the sutures were obtained at 30°, 60°, and 90° of flexion in response to external loads. No significant differences were found between augmentation groups due to tunnel location in terms of ATT or the in situ forces carried by the sutures at all flexion angles tested. Similar results were found under 5 N m of varus-valgus torque. Under a 67 N anterior tibial load, the ATT was restored to within 3 mm of the intact joint following suture augmentation (p > 0.05). Suture augmentation, when placed close to the ACL insertion, could be helpful in providing initial joint stability to aid ACL healing in the goat model., (Published by Wiley Periodicals, Inc. J Orthop Res 28:1373-1379, 2010.)

Primary suture anterior cruciate ligament (ACL) repair was abandoned in favor of reconstruction due to a high rate of clinical failures. However, the insertion of a collagen scaffold loaded with platelets into the wound at the time of suture repair ("enhanced primary repair") has been shown to improve functional healing in animal models. Our objectives were to determine if using a collagen scaffold alone (without platelets) would be sufficient to increase the structural properties of the repaired ACL and decrease postoperative knee laxity compared to suture repair without the scaffold. Eight Yucatan minipigs underwent bilateral ACL transection and suture repair. In one knee, the repair was augmented with a collagen scaffold (SCAFFOLD group) while the other had suture alone (SUTURE group). After 13 weeks of healing, knee joint laxity and the structural properties of the ACL were measured. The addition of the collagen scaffold to suture repair of a transected ACL did not significantly improve the mean anteroposterior knee laxity [SCAFFOLD vs. SUTURE: 6.1 +/- 1.4 vs. 4.4 +/- 2.0 mm (p = 0.07), 8.1 +/- 2.0 vs. 7.6 +/- 2.0 mm (p = 0.66), and 6.2 +/- 1.2 vs. 6.1 +/- 1.8 mm (p = 0.85) at 30 degrees, 60 degrees, and 90 degrees flexion, respectively]. Likewise, there were no significant differences in the structural properties [SCAFFOLD vs. SUTURE: 367 +/- 185.9 vs. 322 +/- 122.0N (p = 0.66) and 90.7 +/- 29.5 vs. 85.0 +/- 30.3N/mm (p = 0.74) for the yield load and linear stiffness, respectively]. The use of a collagen scaffold alone to enhance suture repair of the ACL was ineffective in this animal model. Future work will be directed at stimulating biological activity in the scaffold., ((c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The coefficient of friction (COF) of articular cartilage is thought to increase with osteoarthritis (OA) progression, and this increase may occur due to a decrease in lubricin concentration. The objectives of this study were to measure the COF of guinea pig tibiofemoral joints with different stages of OA and to establish relationships between COF, lubricin concentrations in synovial fluid, and degradation status using the Hartley guinea pig model. Both hind limbs from 24 animals were harvested: seven 3-month-old (no OA), seven 12-month-old (mild OA), and 10 that were euthanized at 12 months of age after undergoing unilateral ACL transection at 3 months of age (moderate OA). Contralateral knees served as age-matched controls. COFs of the tibiofemoral joints were measured using a pendulum apparatus. Synovial fluid lavages were analyzed to determine the concentration and integrity of lubricin using ELISA and Western blot, and the overall articular cartilage status was evaluated by histology. The results showed that the mean COF in the ACL-deficient knees was significantly greater than that of the no OA (p < 0.01) and mild OA knees (p < 0.01). Lubricin concentrations in the ACL-deficient knees were significantly lower than that in both of the other groups (p < 0.01). No significant differences in COF or lubricin concentration were found between the no OA and mild OA knees. Histology verified the extent of cartilage damage in each group., ((c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The purpose of this study was to identify gait asymmetries during the mid-stance phase of gait among subjects with knee instability ("non-copers") after acute anterior cruciate ligament (ACL) rupture. Twenty-one non-copers with acute, isolated ACL injury ambulated at their intentional walking speed as kinetic, kinematic, and electromyographic (EMG) data were collected bilaterally. Lower extremity movement patterns and muscle activity were analyzed during the mid-stance and weight acceptance phases of stance. When compared to the uninjured limb, subjects exhibited lower sagittal plane knee excursions and peak knee angles, and higher muscle co-contraction on the injured limb. There was a lower knee flexion moment at peak knee extension, a trend for the knee contribution to the total support moment to be lower, and a higher ankle contribution to the total support moment on the injured limb. There were differences in the magnitude of muscle activity which included higher hamstring activity and lower soleus activity on the injured limb. Changes in quadriceps, soleus, and hamstring muscle activity on the injured limb were identified during weight acceptance that had not previously been reported, while hip compensation for a lower knee contribution to the total support moment has been described. Non-copers consistently stabilize their knee with a stiffening strategy involving less knee motion and higher muscle contraction. The variable combination of muscle adaptations that produce joint stiffness, and the ability of both the ankle and the hip to compensate for lower knee control indicate the non-coper neuromuscular system may be more malleable than previously believed.

The reason that the anterior cruciate ligament (ACL) has a very poor healing potential after injury is not well understood. In this study, we investigated the role of nitric oxide (NO) in the apoptotic cell death of ACL cells using a rabbit model and in vitro cell culture. The apoptosis of ACL cells in vivo was analyzed by TUNEL assay and electron microscopy. NO synthase (NOS) expression was observed by immunohistochemical analysis. ACL cells were cultured and the susceptibility to NO-induced apoptosis was tested. Inducible NOS (iNOS) expression after treatment with cytokines was examined by immunohistochemical and RT-PCR analyses. Mitogen-activated protein kinase (MAPK) inhibitors were used for the analysis of downstream signals. A significant number of apoptotic cells were observed on days 1 to 3 after injury; the apoptotic rate returned to the control level by day 7. Upregulation of iNOS in the ACL remnant was observed at day 1. Intraarticular injection of NOS inhibitor suppressed the apoptotic rate. Isolated ACL cells showed much higher susceptibility to NO-induced apoptosis than did medial collateral ligament cells. IL-1beta stimulated ACL cells to upregulate iNOS mRNA and increase NO production. p38 MAPK inhibitor decreased NO-induced apoptosis. Rapid iNOS induction after injury contributes to the high apoptotic rate of ACL cells, and this may partly account for the poor healing capacity of this ligament. iNOS and NO production is suggested to be stimulated by IL-1beta, and NO activates the p38 MAPK pathway and triggers an apoptotic signal in ACL cells., (Copyright (c) 2006 Orthopaedic Research Society.)

The anterior cruciate ligament (ACL) of the knee fails to heal after primary repair. Here we hypothesize that a beneficial biologic repair response can be induced by placing a collagen-platelet rich plasma (collagen-PRP) material into a central ACL defect. A collagen-PRP scaffold was used to treat a central ACL defect in vivo. In the first experiment, the histologic response in treated and untreated defects was evaluated at 3 (n = 5) and 6 weeks (n = 5). In the second experiment, biomechanical testing of the treated ligaments (n = 8) was performed at 6 weeks and compared with the results of biomechanical testing of untreated defects at the same time-point (n = 6). The percentage filling of the defects in the treated ACLs was significantly higher at both the 3- and 6-week time-points when compared with the untreated contralateral control defects (50 +/- 21% vs. 2 +/- 2% at 3 weeks, and 43 +/- 11% vs. 23 +/- 11 at 6 weeks; all values mean +/- SEM. Biomechanically, the treated ACL defects had a 40% increase in strength at 6 weeks, which was significantly higher than the 14% increase in strength previously reported for untreated defects (p < 0.02). Placement of a collagen-PRP bridging scaffold in a central ACL defect can stimulate healing of the ACL histologically and biomechanically., (Copyright 2006 Orthopaedic Research Society)

Unicompartmental knee arthroplasty (UKA) has regained popularity in recent years. However, limited data exist on how UKA affects knee biomechanics. The role of the anterior cruciate ligament (ACL) after fixed bearing UKA remains controversial. In this study, a robotic testing system was used to apply a quadriceps/hamstrings load to cadaveric knee specimens in the intact state, after medial UKA, and after transection of the ACL in UKA. The load was applied to the knee from full extension to 120 degrees of flexion in 30 degrees increments. UKA generally did not affect anterior-posterior (AP) femoral position, but did cause external tibial rotation and variations in varus-valgus rotation compared to the intact knee. ACL transection after UKA shifted the femur posteriorly compared to the intact and UKA knees and increased internal tibial rotation compared to the UKA knee at low flexion. The AP motion of the articular contact position in the implant was increased after ACL transection. These data might help explain the mechanism of tibial component loosening and provide insight into further investigations of polyethylene wear in UKA. Based on the kinematic data, the ACL should be functional to provide patients the greatest opportunity for long-term success after medial UKA., (Copyright 2006 Orthopaedic Research Society)

Intra-articular soft tissues, such as the anterior cruciate ligament (ACL), fail to heal in contrast to the extra-articular medial collateral ligament (MCL), which undergoes classic healing. The goal of this study was to validate a model for failure of intra-articular healing that could be used in the future to test new repair strategies. We conducted a two-part experiment, the first part ex vivo, and the second in vivo. Our initial ex vivo experiments were used to determine the optimal width of the central defect in the canine ACL that would produce reproducible structural properties at time zero. The second experimental series used this optimal scalpel blade width to create a central defect in the canine ACL followed by measurement of structural properties in the ACL after either a 3- or 6-week in vivo healing period. A 3.5-mm beaver blade resulted in a maximum tolerated load of 56.8 +/- 4.7% (mean +/- SEM) of control at time zero. After the 3- and 6-week in vivo healing periods, the maximum load was 74.6 +/- 5.3 at 3 weeks and 64.9 +/- 3.8% at 6 weeks compared to control. Thus, biomechanical parameters tested at 6 weeks after creation of a defect showed no significant gains from defects tested immediately after the creation of injury. The centrally placed ACL defect in this canine model demonstrates failure to mechanically heal, which should prove suitable for future in vivo evaluation of the biomechanical and histological response to tissue engineering repair strategies for intra-articular soft tissues., (Copyright 2006 Orthopaedic Research Society.)

Kinematics measured during a short arc quadriceps knee extension exercise were compared in the knees of functionally unstable ACL-deficient patients, these patients' uninjured knees, and uninjured control subjects' knees. Cine phase contrast dynamic magnetic resonance imaging, in combination with a model-based tracking algorithm developed by the authors, was used to measure tibiofemoral kinematics as the subjects performed the active, supine posture knee extension exercise in the terminal 30 degrees of motion. Two determinants of tibiofemoral motion were measured: anterior/posterior location of the tibia relative to the femur, and axial rotation of the tibia relative to the femur. We hypothesized that more anterior tibial positioning, as well as differences in axial tibial rotation patterns, would be observed in ACL-deficient (ACL-D) knees when compared to uninjured knees. Multifactor ANOVA analyses were used to determine the dependence of the kinematic variables on (i) side (injured vs. uninjured, matched by subject in the control group), (ii) flexion angle measured at five-degree increments, and (iii) subject group (ACL-injured vs. control). Statistically significant anterior translation and external tibial rotation (screw home motion) accompanying knee extension were found. The ACL-D knees of the injured group exhibited significantly more anterior tibial positioning than the uninjured knees of these subjects (average difference over extension range=3.4+/-2.8 mm, p<0.01 at all angles compared), as well as the matched knees of the control subjects. There was a significant effect of interaction between side and subject group on A/P tibial position. We did not find significant differences in external tibial rotation associated with ACL deficiency. The changes to active joint kinematics documented in this entirely noninvasive study may contribute to cartilage degradation in ACL-D knees, and encourage more extensive investigations using similar methodology in the future., ((c) 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.)

Purpose: The purpose of this study is to evaluate the Rolimeter knee tester (Aircast, Europe) as reliable and clinically sensitive tool for identifying and quantifying knee joint laxity utilising a sample of both known ACLD and normal knees., Methods: Thirty matched subjects (15 known ACLD and 15 normal subjects) were tested for knee joint laxity using the Rolimeter. Each subject was measured at both 90 degrees and 30 degrees of knee flexion, by each of the six investigators. This was then repeated again by all six investigators so that inter-tester and intra-tester reliability could be examined., Results: Results showed that there was good reliability between testers, and intra-tester reliability was good for both left and right knees in both 90 degrees and 30 degrees of flexion. Results also demonstrated a high level of sensitivity for determining knee joint laxity in ACLD compared to normal knees., Conclusion: The Rolimeter knee tester is a reliable device for quantifying knee joint laxity, and is sensitive enough to identify anterior cruciate ligament deficiency.

The ideal treatment of a combined anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injury to the knee is still debated. In particular, the question of whether reconstruction of the ACL can provide the knee with sufficient multidirectional stability to allow for effective MCL healing needs to be better elucidated. Therefore, the first objective of this study was to quantify the changes in the function of goat knees between time-zero and 6 weeks following a combined ACL/MCL injury treated with ACL reconstruction. Using a robotic/universal force-moment sensor testing system, the kinematics of the knee and in situ forces in the ACL/ACL graft as well as in the sham-operated and healing MCL were evaluated in response to (1) a 67 N anterior-posterior (A-P) tibial load and (2) a 5 Nm varus-valgus (V-V) moment. The second objective was to evaluate the structural properties of the healing femur-MCL-tibia complex (FMTC) and the mechanical properties of the healing MCL at 6 weeks under uniaxial tension. In response to the 67 N A-P tibial load, the A-P translations for the experimental knee increased by as much as 4.5 times from time-zero to 6 weeks (p<0.05). Correspondingly, the in situ forces in the ACL graft decreased by as much as 45% (p<0.05). There was no measurable changes of the in situ force in the healing MCL. In response to a 5 Nm V-V moment, V-V rotations were twice as much as controls, but similar for both time periods. From time-zero to 6 weeks, the in situ forces in the ACL graft dropped by over 71% (p<0.05), while the in situ force in the healing MCL was as much as 35+/-19 N. In terms of the structural properties of the healing FMTC, the stiffness and ultimate load values at 6 weeks reached 53% and 29% of sham-operated contralateral controls, respectively (p<0.05). For the mechanical properties of the healing MCL substance, the values for tangent modulus and tensile strength were only 13% and 10% of sham-operated controls, respectively (p<0.05). These results suggest that the ACL graft stabilized the knee initially, but became loose over time. As a result, the healing MCL may have been required to take on excessive loads and was unable to heal sufficiently as compared to an isolated MCL injury.

Neuromuscular control is believed to be a critical factor in dynamic knee stability. The purpose of this study was to evaluate voluntary muscle control in anterior cruciate ligament deficient (ACL-D) and uninjured people. Twenty athletes of similar age participated in this study. Subjects performed a target-matching protocol that required them to produce isometric moments about the knee with fine control in flexion, extension, varus, and valgus (i.e., loads were generated in the plane perpendicular to the long axis of the shank). Electromyographic data were collected from 10 muscles that span the knee. A specificity index was calculated for each muscle to describe how fine-tuned (specific) its muscle activity pattern was with respect to its principal direction of action in the load plane. Diminished specificity of muscle action was observed in 8 of 10 muscles in the ACL-D subjects' involved knees when compared with the activity patterns from their uninvolved knees and those from the uninjured subjects' knees. The vastus lateralis muscle was especially affected. Increased and more global co-contraction was also observed in the ACL-D limbs. The alterations in muscle firing patterns observed in this study are consistent with diminished neuromuscular control.

In clinical terms, functional recovery after anterior cruciate ligament (ACL) injury is generally poorer than after medial collateral ligament (MCL) injury. In experimental studies of injury, the early phases of ligament healing require an augmented blood supply. We hypothesized that the differences in healing properties of the ACL and MCL would be reflected in the magnitude of their vascular responses to partial injury. This study is the first to quantify and define the time course of changes in blood flow and vascular volume following hemisection of the rabbit ACL and MCL. Adult female rabbits were assigned to control, sham operation, ACL hemisection or MCL hemisection groups. Standardized ACL or MCL injuries were surgically induced. About 2, 6 or 16 weeks later, blood flow and vascular volume of the ACL and MCL were measured. The MCL of the rabbit responded to hemisection with a large significant increase in blood flow and a substantial angiogenic response associated with inflammation and scar formation. During subsequent matrix remodelling, blood flow and vascular volume returned towards control values. In contrast, the ACL showed only a 2-fold increase in vascular volume, no increase in blood flow and atrophied after hemisection. The superior capacity of the MCL to increase its blood supply through angiogenesis and increased flow is essential for ligament healing to occur, and may be the major difference in healing potential between the ACL and MCL.

Transection of the canine anterior cruciate ligament (ACL) is a well-established osteoarthritis (OA) model. This study evaluated a new method of canine ACL disruption as well as canine knee joint laxity and joint capsule (JC) contribution to joint stability at two time points (16 and 26 weeks) after ACL disruption (n=5/time interval). Ten crossbreed hounds were evaluated with force plate gait analysis and radiographs at intervals up to 34 weeks after monopolar radiofrequency energy (MRFE) treatment of one randomly selected ACL. Each contralateral ACL was sham treated. The MRFE treated ACLs ruptured approximately eight weeks (mean 52.5 days, SEM+/-1.0, range 48-56 days) after treatment. Gait analysis and radiographic changes were consistent with established canine ACL transection models of OA. Anterior-posterior (AP) translation and medial-lateral (ML) rotation were measured in each knee at 30 degrees, 60 degrees, and 90 degrees of flexion with and then without JC with loads of 40 N in AP translation and 4 Nm in ML rotation. A statistically significant interaction in AP translation included JC by cruciate (P=0.02), and there was a trend for a cruciate by time (P=0.07) interaction. Significant interactions in ML rotational testing included the presence of joint capsule (P=0.0001) and angle by cruciate (P=0.0012). This study describes a model in which canine ACLs predictably rupture approximately eight weeks after arthroscopic surgery and details the contribution of JC to canine knee stability in both ACL intact and deficient knees. The model presented here avoids the introduction of potential surgical variables at the time of ACL rupture and may contribute to studies of OA pathogenesis and inhibition. This model may also be useful for insight into the pathologic changes that occur in the knee as the ACL undergoes degeneration prior to rupture.

Functional outcomes of anterior cruciate ligament (ACL) injury are generally poorer than those of medial collateral ligament (MCL) tears. Following ligament damage, all phases of ligament healing require an adequate blood supply. We hypothesized that the differences in healing properties of the ACL and MCL would reflect their vascular responses to joint injury. This paper examines the long-term changes in blood flow and vascular volume of rabbit knee ligaments after direct injury, and under conditions of chronic joint instability induced by section of the posterior cruciate ligament (PCL). Standardized injuries were surgically induced in adult rabbit knee ligaments: partial MCL transection, partial ACL transection, or complete PCL transection (joint instability). Sixteen weeks later the blood flow and vascular volume of the ACL and MCL were measured and compared to control and sham-operated animals. Direct ligament injury induced significant increases in standardized blood flow and vascular volume of both ACL and MCL after 16 weeks; however, the vascular volume of the ACL was not higher than the control levels in the MCL. We conclude that direct injury to both the anterior cruciate and MCLs induces long-term physiological responses. Joint laxity is a common sequel to PCL injury. Chronic joint laxity failed to induce adaptive vascular responses in the ACL, while the MCL shows significant amplification of blood supply. Although both MCL and ACL showed increased weight after PCL transection, the lack of a long-term vascular response in the ACL may be a major factor in its the diminished healing potential.

The purpose of this study was to measure the effects of variation in placement of the femoral tunnel upon knee laxity, graft pretension required to restore normal anterior-posterior (AP) laxity and graft forces following anterior cruciate ligament (ACL) reconstruction. Two variants in tunnel position were studied: (1) AP position along the medial border of the lateral femoral condyle (at a standard 11 o'clock notch orientation) and (2) orientation along the arc of the femoral notch (o'clock position) at a fixed distance of 6-7 mm anterior to the posterior wall. AP laxity and forces in the native ACL were measured in fresh frozen cadaveric knee specimens during passive knee flexion-extension under the following modes of tibial loading: no external tibial force, anterior tibial force, varus-valgus moment, and internal-external tibial torque. One group (15 specimens) was used to determine effects of AP tunnel placement, while a second group (14 specimens) was used to study variations in o'clock position of the femoral tunnel within the femoral notch. A bone-patellar tendon-bone graft was placed into a femoral tunnel centered at a point 6-7 mm anterior to the posterior wall at the 11 o'clock position in the femoral notch. A graft pretension was determined such that AP laxity of the knee at 30 deg of flexion was restored to within 1 mm of normal; this was termed the laxity match pretension. All tests were repeated with a graft in the standard 11 o'clock tunnel, and then with a graft in tunnels placed at other selected positions. Varying placement of the femoral tunnel 1 h clockwise or counterclockwise from the 11 o'clock position did not significantly affect any biomechanical parameter measured in this study, nor did placing the graft 2.5 mm posteriorly within the standard 11 o'clock femoral tunnel. Placing the graft in a tunnel 5.0 mm anterior to the standard 11 o'clock tunnel increased the mean laxity match pretension by 16.8 N (62%) and produced a knee which was on average 1.7 mm more lax than normal at 10 deg of flexion and 4.2 mm less lax at 90 deg. During passive knee flexion-extension testing, mean graft forces with the 5.0 mm anterior tunnel were significantly higher than corresponding means with the standard 11 o'clock tunnel between 40 and 90 deg of flexion for all modes of constant tibial loading. These results indicate that AP positioning of the femoral tunnel at the 11 o'clock position is more critical than o'clock positioning in terms of restoring normal levels of graft force and knee laxity profiles at the time of ACL reconstruction.

We studied how initial graft size and initial graft laxity affected the biomechanics of anterior cruciate ligament (ACL) reconstruction at six months. Sixteen goats had bilateral reconstructions staged eight weeks apart. Autografts 4 and 7 mm wide were taken from the central patellar tendon (PT). Lax grafts were created by adding 4 mm slack to the graft before fixing. We reconstructed each joint using a combination of width and laxity treatments. Both factors were changed for the contralateral joint and all combinations appeared with equal frequency. At six months we measured the joint extension limit, anterior-posterior (AP) translation, and osteoarthritic changes. The grafts were then tested to failure to determine their mechanical properties. After six months the difference in initial treatments had disappeared: there was no difference in graft cross-section due to the different initial widths and there was no difference in joint AP translation due to the initial graft laxity. We did observe that wide grafts were associated with a block to extension, decreased joint AP translation, and increased articular cartilage damage and osteophyte formation. While AP translation was reduced, it was correlated with decreased extension, possibly indicating an increase in scar tissue formation rather than a more functional graft. Neither graft width nor graft laxity produced differences in any graft mechanical properties. This suggests that the use of larger grafts to prevent increased AP translation has undesirable complications. Ultimately, we conclude that neither of these surgical treatments strongly affects the biomechanical result of caprine ACL reconstruction.

In this study, an ex vivo organ culture system that allows the application of controlled loads to the anterior cruciate ligament (ACL) was designed and used to characterize the influence of a step input in mechanical load on gene expression. A procedure for isolating bone-ACL-bone (B-ACL-B) complexes from rat knees was developed. After harvest and 24 hour culture, B-ACL-B complexes exhibited percentages of viability similar to that in intact ACLs (approximately 90%). Application of a physiologically relevant load of 5 N (superimposed on a I N tare load) resulted in changes in levels of mRNA encoding type I collagen. While levels of type I collagen mRNA significantly increased 32+/-13% (mean +/- standard errors of the mean (SEM)) over controls within the first hour of loading, levels decreased significantly to 44+/-9% of control after 2 h. Displacements induced by the 5 N load were measured by video dimensional analysis. Calculated axial strains of 0.141+/-0.034 were achieved rapidly during the first hour and remained essentially unchanged thereafter. These results demonstrate the feasibility of maintaining ligaments in organ culture and illustrate the time course expression of type I collagen following the application of a mechanical load.

Relatively little is known about the cellular and molecular responses of the knee joint meniscus to joint injury, despite the functional importance of the tissue. We investigated how meniscus cells respond to joint injury in the early stages of post-traumatic osteoarthritis by characterizing the changes in matrix gene expression in menisci at 3 and 12 weeks post-surgery in dogs in which the anterior cruciate ligament (ACL) in one joint was transected and the other unoperated joint served as a control. Changes in the total RNA and DNA concentrations of the menisci were determined. Absolute concentrations of the mRNA of the COL1A1 gene of type 1 collagen, the major fibrillar collagen of the meniscus, and the COL6A3 gene of type VI collagen, a major repair molecule, were determined by quantitative ribonuclease (RNase) protection assay. The concentration of total RNA in medial and lateral menisci increased from 40 to 60 microg RNA/g wet wt in unoperated, control joints to 200-350 microg RNA/g wet wt in ACL-deficient joints. No significant changes were detected in the concentration of DNA (900-1200 microg DNA/g wet wt). Low concentrations of COL1A1 (2-3 pmol mRNA/g DNA) and COL6A3 (0.3-0.6 pmol mRNA/g DNA) mRNA transcripts were measured in normal menisci. ACL-deficiency induced a 20-38 fold increase in COL1A1 and COL6A3 mRNA concentration at 3 weeks, and an 11-19 fold increase at 12 weeks post-surgery. In general, the increase in COL1A1 and COL6A3 mRNA concentrations was greater in medial menisci than in lateral menisci. These results demonstrate that the menisci initiate a vigorous biosynthetic response to transection of the ACL.

Experimental models are often used in the laboratory to produce incomplete soft-tissue injuries simulating those observed clinically. Single and incremental stretch protocols have been utilized. The latter has many advantages over the former. This study was designed to determine if incremental and single ligamentous stretches are biomechanically equivalent. Eleven paired fresh rabbit bone-anterior cruciate ligament-bone preparations were used. One of each pair (single-stretch protocol) was stretched to 88% of the average failure deformation and then stretched to failure. The other ligament (incremental-stretch protocol) was stretched to 55, 66, 77, and 88% of the average failure deformation and then stretched to failure. All stretches were performed at 1.2 m/sec. Stress-relaxation tests were performed before and after the 88% stretch for both stretch protocols. Relaxation curves were parameterized as forces at six time points and were also fitted to a three-element model. Load-deformation curves recorded during stretch to failure were characterized by eight parameters. Each incremental stretch step produced a significant increase in deformation, indicating alteration in the mechanical properties of the ligament. Both groups of ligaments, when intact, exhibited no differences in relaxation curves (p > 0.2). The 88% stretches, produced by each of the two stretch protocols, significantly altered the viscoelastic behavior of the ligaments (p < 0.002). However, after the 88% stretch, there were no differences in either viscoelastic (p > 0.1) or load-deformation (p > 0.1) parameters of the two stretch protocols. In conclusion, the 88% subfailure stretch significantly altered the mechanical properties of ligament, and the incremental and single stretches were biomechanically equivalent.

We compared the mechanical behavior of two common hamstring graft constructs that are frequently used for reconstruction of the anterior cruciate ligament-Graft A: quadrupled semitendinosus tendon fixed with titanium button/polyester tape and suture/screw post, and Graft B: a double semitendinosus and double gracilis tendon fixed with a cross pin and two screws over washers. The experimental protocol used to evaluate each graft construct included stress relaxation (with and without preconditioning), cyclic loading, and a tensile load-to-failure test. The amount of stress relaxation without preconditioning was 60.6% for Graft A and 53.8% for Graft B. With preconditioning, it significantly decreased (p < 0.05) to 48.7 and 42.3%, respectively. Elongation of the graft construct in response to 100 cycles of loading (20-150 N) was 1.8 and 0.6% of the original length for Grafts A and B, respectively. However, after a series of five cyclic loading tests, the residual permanent elongation for each construct was 3.8 +/- 1.2 and 0.3 +/- 0.2 mm, a significant difference (p < 0.05) between the two graft constructs. Further analysis found more than 90% of the permanent elongation in the proximal and distal regions of Graft A, which consisted of polyester tape tied to a titanium button (proximal) and sutures tied around a screw post (distal). The tensile load-to-failure tests also revealed significant differences (p < 0.05) between the two graft constructs. Linear stiffness was 32 +/- 1 and 119 +/- 19 Nmm and ultimate load was 415 +/- 36 and 658 +/- 128 N for Grafts A and B, respectively. For Graft A, the polyester tape consistently failed; for Graft B, slippage or tearing from the washers was the mode of failure. We conclude that a quadruple-hamstring graft fixed over a cross pin proximally and with metal washers distally (Graft B) has less permanent elongation in response to cyclic loading and has structural properties superior to those of a graft construct that includes suture and tape material (Graft A). The large permanent elongation following repetitive loading of a graft construct with tape and suture material during the early postoperative period is of concern.

Passive anterior-posterior displacement and medial-lateral rotation of the tibia on the femur in the feline knee were assessed before transection of the anterior cruciate ligament, immediately after transection, and 2 and 4 months after transection. Four anaesthetized experimental and three sham-operated control animals were positioned in a stereotaxic frame. Motions of the tibia relative to the femur were measured with use of 60-Hz video motion analysis, while a strain-gauged system allowed measurement of forces and moments applied to the tibia. Displacement at 15 N of anterior force and 30 degrees of knee flexion increased by an average of 6 mm following transection, and stiffness decreased by an average of 6 N/mm. At 2 and 4 months following transection, there were statistically significant reductions in this abnormal displacement. Stiffness during anterior displacement of the tibia at 30 degrees increased significantly from immediately after transection to 4 months. At 90 degrees, mean anterior displacement decreased from 5.1 mm immediately after transection to 2.9 mm at 4 months. Medial rotation at 30 degrees of knee flexion was significantly decreased from a mean of 16.5 degrees after transection to a mean of 10.7 degrees at 4 months. Changes in medial rotation at 90 degrees, lateral rotation at 90 degrees, and lateral rotation at 30 degrees were not statistically significant. These results indicate a significant change in secondary constraints to tibial motion in response to knee instability.

The purpose of this study was to develop a method to prospectively quantify passive knee stability in an animal model of joint injury over time. Knee stability is defined here as the amount of translation or rotation of the tibia relative to the femur for a given application of force or moment, respectively. Five animals that had undergone transection of the anterior cruciate ligament and three control animals that had undergone a sham operation were anaesthetized and positioned in a stereotaxic frame. Motion of the tibia relative to the femur was quantified with use of reflective markers secured to modified bone pins and a three-dimensional motion analysis system. External forces and moments in the transverse plane of the tibia were measured with use of force transducers based on a strain-gauge design. Longitudinal measurements of knee stability were made before either sham surgery (control animals) or transection of the ligament (experimental animals), immediately after surgery, and at 2 and 4 months after transection. The results showed that the animals tolerated the procedures well and that systematic measurements could be obtained. The method described here has the practical advantage over cross-sectional experimental designs in that the number of subjects can be decreased while maintaining statistical power and has the further conceptual advantage that individual changes can be accounted for over time.

A defect in proprioception has been found in selected patient groups that have an anterior cruciate ligament deficient knee at different times after the original injury. The time of development and the extent of such defects were studied longitudinally on 16 consecutive patients. During the first year after a primary knee injury, which included a complete rupture of the anterior cruciate ligament, we repeatedly performed three tests of proprioception: (a) one to determine the threshold for detecting a passive motion from starting positions of 20 and 40 degrees, (b) an active reproduction of a passive angular change, and (c) a visual estimation of a passive angular change. The injured limb was compared with the uninjured limb and with the limbs of an age-matched reference group of healthy subjects. The population did not have a normal distribution, and some patients had consistently extreme recordings in the threshold tests at the various times of testing. Significant differences were found between the groups at the starting position of 20 degrees, when the injured knee was compared with the uninjured knee, after 1 month (p = 0.05), and after 2 months (p = 0.03). There was a trend toward a higher threshold for detecting a passive motion when the injured side was compared with the knees of the reference group at 1 month (p = 0.06) but not later on. A similar pattern was found for the injured knee at the starting position of 40 degrees, but it was not significant. An impaired ability to detect a passive motion was registered for the nearly extended knee 1 and 2 months after a primary injury. In the active reproduction and visual estimation tests, no significant defects were found at any time during the first year in these consecutively studied patients.

It is well documented that the adult human medial collateral ligament has a functional healing response, whereas the anterior cruciate ligament does not. The differential healing responses of the medial collateral and anterior cruciate ligaments could be due to factors caused by different biological conditions and locations in vivo. In addition, different intrinsic properties of the constituent cells of these ligaments may contribute to their different healing abilities. Ligament healing follows an orderly process of hemorrhage, inflammation, proliferation, and remodeling. At the cellular level, healing involves a cell's detachment from and attachment to the matrix adjacent to the wound area, migration, and proliferation. This study sought to investigate whether, during migration, the responses of the medial collateral and anterior cruciate ligament fibroblasts are intrinsically different under the same inflammatory conditions. Human medial collateral and anterior cruciate ligament fibroblast cells were cultured, and in vitro wounds were simulated by streaking the cells with an inoculating loop, creating a cell-free area. The migration of the cells into this gap, thus filling the cell-free area, was observed. Two sets of experiments were conducted; one varied the wound width and the other added the inflammatory factors tumor necrosis factor-alpha, complement C5a, and lipopolysaccharide. As the width of the wound increased, the rate of recovery decreased for both types of ligament cells (slope: anterior cruciate ligament, 0.13 hour/micron and medial collateral ligament, 0.10 hour/micron). Also, the three inflammatory factors used all inhibited the recovery rates of both ligaments to ones that were 1.4-2.3 times slower than controls. However, in both sets of experiments, the anterior cruciate ligament fibroblasts were more sensitive to inflammatory factors, and the medial collateral ligament fibroblasts had faster recovery rates (anterior cruciate ligament, 1.2-3.4 times slower than rates for medial collateral ligament fibroblasts, excluding those under lipopolysaccharide treatment). The results showed that medial collateral and anterior cruciate ligament fibroblasts responded differently under the same inflammatory conditions. This may suggest that these differences in intrinsic properties contribute to their different healing responses and abilities.

This study examined the change in type-III collagen concentration and hydroxypyridinium crosslink density of anterior cruciate ligament-patellar tendon autografts and their correlations with Young's modulus of the anterior cruciate autografts and anterior cruciate controls for as long as 3 years after surgery. Fifteen adult female goats (two control and 13 experimental) were tested. Each experimental animal received an anterior cruciate ligament-patellar tendon autograft to the right knee. These animals were tested at 0 (n = 2), 6 (n = 2), 12 (n = 2), and 24 (n = 1) weeks and 1 (n = 3) and 3 (n = 3) years after surgery. After mechanical testing, the anterior cruciate autograft and control tissues were analysed for type-III collagen concentration and hydroxypyridinium crosslink density. The results of sodium dodecyl sulfate gel electrophoresis showed a trend of initial increase in the percentage of type-III collagen in the anterior cruciate ligament autografts and a subsequent decrease after 24 weeks following surgery. There was a nonsignificant (p > 0.05) negative correlation between type-III collagen concentration and Young's modulus. The hydroxypyridinium crosslink density was highest at 1 year after surgery. There was a significant (p < 0.05) positive correlation between hydroxypyridinium crosslink density and Young's modulus in the anterior cruciate autografts and controls. This suggests that hydroxypyridinium crosslink density has a good linear relationship with the material strength of the anterior cruciate ligament autograft and hence could be used as an objective guide for rehabilitation with anterior cruciate autografts.

Ligamentous injuries range in severity from a simple sprain to a complete rupture. Although sprains occur more frequently than complete failures, only a few studies have investigated the phenomena of these subfailure injuries. The purpose of our study was to document the changes in the load-deformation curve until the failure point, after the ligament has been subjected to an 80% subfailure stretch. Thirteen paired fresh rabbit bone-anterior cruciate ligament-bone preparations were used. One of the pairs (control) was stretched until failure; the other (experimental) was first stretched to 80% of the failure deformation of the control and then stretched to failure. Comparisons were made between the load-deformation curves of the experimental and control specimens. The nonlinear load-deformation curves were characterized by eight parameters: failure load (Ffail), failure deformation (Dfail), energy until failure (Efail), deformations measured at 5, 10, 25, and 50% of the failure load (D5, D10, D25, and D50, respectively), and stiffness measured at 50% of the failure force (K50). There were no significant differences in the values for Ffail, Dfail, and Efail between the experimental and control ligaments (p > 0.33). In contrast, the deformation values were all larger for the experimental than the control ligaments (p > 0.01). The deformations D5, D10, D25, and D50 (mean +/- SD) for the control were 0.36 +/- 0.13, 0.49 +/- 0.23, 0.81 +/- 0.35, and 1.23 +/- 0.41 mm. The corresponding deformations for the experimental ligaments were, respectively, 209, 186, 153, and 130% of the control values. K50 was also greater for the experimental ligament (125.0 +/- 41.7 N/mm compared with 108.7 +/- 31.4 N/mm, p < 0.03). These findings indicate that even though the strength of the ligament did not change due to a subfailure injury, the shape of the load-displacement curve, especially at low loads, was significantly altered. Under the dynamic in vivo loading conditions of daily living, this may result in increased joint laxity, additional loads being applied to other joint structures, and, with time, to joint problems.

Neuromuscular electrical stimulation and voluntary muscle contraction are two exercise modes widely used in rehabilitation to strengthen skeletal muscle. Since there is no debate as to which mode is most effective, we compared electrical stimulation with voluntary contraction performed at matched intensities following reconstructive surgery of the anterior cruciate ligament. Forty men and women, aged 15-44, were randomly assigned to either an electrical stimulation or a voluntary contraction group. None of the subjects had a previous history of neuromuscular injury. The subjects received treatment for 30 minutes a day, 5 days a week, for 4 weeks. Knee extension torque was monitored during treatment to try to match the absolute muscular tensions (quantified as "activity") achieved during therapy. To match the activity of the subjects in the electrical stimulation group, who were treated at the highest stimulation intensity they could tolerate, the subjects in the voluntary contraction group were paced at progressively increasing intensities corresponding to 15, 25, 35, and 45% of the injured limb's maximum voluntary torque during weeks 1, 2, 3, and 4, respectively. We found no significant difference between the groups in terms of maximum voluntary knee extension torque throughout the study period. In addition, 1 year after surgery, there was still no significant difference between groups with regard to knee extension torque (p > 0.4). These data suggest that neuromuscular electrical stimulation and voluntary muscle contraction treatments, when performed at the same intensity, are equally effective in strengthening skeletal muscle that has been weakened by surgical repair of the anterior cruciate ligament.

The flow-independent viscoelastic and equilibrium behaviors of canine articular cartilage were examined with time after transection of the anterior cruciate ligament. The equilibrium, transient, and dynamic shear behaviors of cartilage were studied in biaxial compression-torsion testing at two time periods after transection of the anterior cruciate ligament and at two sites on the femoral condyle, in order to test for differences between sites of frequent and less frequent contact. Water content also was measured in cartilage at sites corresponding to the areas of mechanical testing. Transection of the anterior cruciate ligament produced significant decreases in all measured moduli of articular cartilage tested in equilibrium and dynamic shear and in equilibrium compression; the values for these moduli were 61, 56, and 77% of the control values, respectively, beginning at 6 weeks following transection of the anterior cruciate ligament. There was evidence of increased energy dissipation of cartilage in shear, with a 13 and 35% increase in tan delta at 6 and 12 weeks after transection of the anterior cruciate ligament, respectively. Changes in the viscoelastic relaxation function of cartilage in shear also were evident at 12 weeks after surgery. In all tissue, there was a significant increase in hydration of approximately 4% at 6 or 12 weeks after surgery. There was little difference between the material parameters for areas considered to be in frequent and less frequent contact, with the exception of hydration, which was greater for areas of less frequent contact.(ABSTRACT TRUNCATED AT 250 WORDS)

The optimal treatment for a combined injury of the medial collateral and anterior cruciate ligaments is controversial, and the question remains as to whether repair of the medial collateral ligament and reconstruction of the anterior cruciate ligament improves healing of the medial collateral ligament. We compared reconstruction of the anterior cruciate ligament with and without repair of the medial collateral ligament in a rabbit model of a combined injury of these two ligaments. The anterior-posterior translation and varus-valgus rotation of the knee, the structural properties of the femur-medial collateral ligament-tibia complex, and the mechanical properties of the midsubstance of the medial collateral ligament were evaluated immediately after surgery and at 6 and 12 weeks postoperatively. Repair of the medial collateral ligament led to significantly less varus-valgus rotation of the knee than did no repair, but the anterior-posterior translation of the knees in the repair and nonrepair groups were not significantly different at any study time. At 12 weeks, the cross-sectional area and ultimate load in the repair group were 60 and 53% greater, respectively, than in the nonrepair group. Among 12 specimens that were repaired (six specimens at 6 weeks and six specimens at 12 weeks), failure occurred within the midsubstance in four (two at each time period); in all of the specimens that were not repaired, failure occurred at the tibial insertion site. There was no significant difference between the modulus of the modulus of the midsubstance in the repaired and the nonrepaired medial collateral ligaments.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of immobilization of the knee joint on the mechanical and ultrastructural properties of the anterior cruciate ligament have not been well documented. Our goal was to determine these effects in a rabbit model and to assess the effect of knee flexion angle during immobilization. The knee joint was immobilized in either 170 degrees or 105 degrees of flexion, and new methodologies were utilized to determine the mechanical properties of the anterior cruciate ligament. In specimens from knees that had been immobilized, the cross-sectional area of the ligament was 74% of the control value. The stress-strain curve was altered slightly, and the strain at failure increased 32-40%. The modulus and stress at failure did not decrease significantly. There was no significant difference between the mechanical properties of the knees immobilized at 170 degrees and 105 degrees of flexion. Histological and ultrastructural evaluation demonstrated changes in the shape and intracellular make-up of the fibroblasts from the ligament after immobilization. This cellular response may account for the alterations in the mechanical properties of the anterior cruciate ligament.

In order to determine the appropriate load history for optimal remodeling of an anterior cruciate ligament graft, methods for establishing and measuring the graft force due to an external load could be set to a preselected value in in vivo are required. Our objectives with this study were to (a) develop a method in which the graft force due to an external load could be set to a preselected value in a living animal, (b) show that this force could be maintained after fixation, and (c) determine what happens to the forces after the animal has functioned for as long as 2 weeks postoperatively, when differing levels of load sharing between the segments had been set at surgery. The anterior cruciate ligament was reconstructed in 12 goats with use of a bone-patellar tendon-bone graft and a synthetic augmentation device. The forces in the graft segments were established, at the time of surgical fixation, with use of a force-setting technique. In five animals, the tendon segment was set to carry 90% of the total graft force; in the remaining seven animals, the augmentation segment was set to share 90% of the total graft force. Graft forces were measured, with the use of buckle transducers mounted extra-articularly over the anterior tibia, under a 67 N anterior tibial load at 60 degrees of knee flexion before and after fixation and at 2 weeks postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Total anterior-posterior translation is commonly used to assess the integrity of the cruciate ligaments and the success of reconstructive surgery. The purpose of this study was to determine, after surgical reconstruction of the anterior cruciate ligament with a biological graft, if total anterior-posterior translation correlated with graft length, cross-sectional area, or mechanical properties. These factors were investigated by analyzing data from three previous studies. These studies involved replacement of the anterior cruciate ligament in cynomolgus monkeys and goats, with free and vascularized patellar tendon autografts and both patellar tendon and anterior cruciate ligament allografts. Data were available at time periods of 6 and 12 months after surgery. We found statistically significant inverse correlations between the amount of anterior-posterior translation and cross-sectional area of a graft at the time of sacrifice. The Pearson correlation coefficients ranged from -0.966 (p < 0.002) to -0.830 (p < 0.05). We hypothesize that these correlations result from the following mechanism: the increased anterior translation reflects a slack graft; a slack graft is stress shielded by other structures about the knee; the reduced in vivo stresses on the graft modulate cellular metabolism in a way that over time produces a small cross-sectional area.

The objective of this study was to analyze the biomechanical effect of varying the level of prescribed load sharing between two segments of an anterior cruciate ligament (ACL) graft, and of separating the femoral attachments of these segments. Total anterior-posterior (AP) laxity was measured using an instrumented spatial linkage. Forces in graft segments were measured using buckle transducers. The two-segment graft was formed using the middle third of the patellar tendon with bone blocks and a synthetic augmentation device. Proximal fixation was obtained using a fixture which allowed changing the individual locations of the femoral attachments of the tendon and augmentation segments. Distal fixation was achieved using a force-setting device which allowed the loads in each segment to be set to prescribed levels. Total graft force, load sharing, and total AP laxity were recorded during the application of 100-N AP tibial loads at 0 degrees, 30 degrees, 60 degrees, 90 degrees, and 110 degrees flexion, for various combinations of load sharing set at extension and locations of femoral attachment sites. The load sharing, total graft force, and AP laxity during AP loading at the five test flexion angles were not significantly affected by changing the prescribed level of load sharing set at extension for a given femoral attachment configuration. However, varying the separate hole locations of the graft segments for a given level of load sharing significantly affected load sharing, total graft force, and AP laxity. If the tendon graft was located posteriorly (on the medial surface of the lateral femoral condyle) and the augmentation segment proximally, the augmentation carried a greater portion of the total force in flexion. If the augmentation segment was changed to a more posterosuperior location and the tendon posteroinferior, the tendon carried a higher percentage of the total force in flexion. AP laxity in most reconstruction states was significantly greater than in the normal joint with an intact ACL. The nature of the load sharing between the graft segments under AP tibial load over the flexion range can be controlled by the appropriate choice of the segments' femoral attachment locations.

We wished to determine the optimal tension required to restore normal joint laxity to anterior cruciate ligament (ACL)-deficient knees using a braided polyethylene ACL prosthesis (PACL). In 10 cadaveric specimens, we measured the anteroposterior (AP) laxity of the intact knee at 10 degrees, 30 degrees, 60 degrees, and 90 degrees of flexion. The ACL was then removed and replaced with the PACL using tunnel-tunnel (T-T) and "over-the-top" (OTT) placement techniques. In both positions, the PACL was initially tensioned to 0, 9, 18, and 27 N with the knee flexed to 30 degrees. AP joint laxity was then measured at each flexion angle. With an increase in initial tension, there was a corresponding decrease in AP laxity. At 30 degrees and 90 degrees of flexion, AP laxity was not significantly different from normal using T-T placement and an initial tension of 0 N. At 90 degrees of flexion, AP laxity was not significantly different from normal using OTT placement at 0 or 9 N of initial tension. For both positions, all other tension levels and flexion angles constrained AP laxity. No laxity differences were detected between the OTT and T-T positions at any flexion angle. The variability in AP laxity of the T-T position was significantly greater than OTT. With a 150-N anterior shear force applied to the proximal tibia, the maximum tensions developed in the PACL were not significantly different between the two positions except at 90 degrees. The results suggest that implantation of the PACL is best performed using OTT positioning with an initial tension of 0 N applied at 30 degrees of knee flexion.

In this study, the short-term effects of immobilization on joint damage and medial collateral ligament (MCL) healing were investigated in unstable, anterior cruciate ligament (ACL)-deficient knees in rabbits. Forty-six 12-month-old female New Zealand white rabbits were separated into three groups. Animals from each group had surgery on their right knees: group I, sham controls (n = 9); group II, complete transection of the ACL and removal of a 4 mm segment (gap injury) of MCL midsubstance with no immobilization of the limb (n = 19); and group III, same injuries to the ACL and MCL (as group II) but with immobilization of the limb (n = 18). No surgical repair of disrupted ligaments was performed. Left knees served as unoperated contralateral controls. All animals were allowed unrestricted cage activity until sacrifice in subgroups at 3, 6, and 14 weeks of healing when biomechanical properties of all MCLs were measured. All knee joints were systematically examined for gross evidence of damage to articular cartilage, menisci, and periarticular soft tissues. To monitor relative in vivo loads on injured limbs during healing, hindlimb weight bearing was assessed at biweekly intervals. Results indicated that animals in both groups II and III bore relatively lower loads (compared to preinjury values) on their injured hindlimbs. Mechanical testing of MCLs showed only minor changes in sham controls, while group II and III healing MCLs demonstrated significantly lower force and stress at MCL complex failure compared to contralateral controls. In specific comparisons of group III to group II animals, we noted that immobilization prevented joint damage over the early intervals studied. In addition, immobilization resulted in MCL laxity similar to contralateral control values but inhibited development of structural strength and stiffness in healing MCLs. These results suggest that in the rabbit, short-term immobilization of an ACL-deficient knee offers some advantages to the joint and to certain low load behaviors of the healing MCL, but it also results in a smaller quantity of scar tissue that is less able to resist higher loads. Longer-term studies involving remobilization are necessary before the effects of brief immobilization on joint damage and MCL healing in this ACL-deficient model can be fully defined.

We wished to determine whether anterior cruciate ligament (ACL) injury caused changes in patterns of activity of individual or groups of muscles that control the knee joint. The electromyographic (EMG) patterns of six muscles in 26 individuals with uninjured knees and 20 individuals with ruptured ACL were studied during free and fast speed walking. A previously developed clustering technique was used for analysis. This technique involves making the Fourier transform of the average linear envelope (LE) of each muscle for each subject and using the amplitude and phase angles of the lower frequency harmonics as features to describe a pattern. These features are then grouped to subdivide the population of EMG patterns into different types. The results of analyses on single muscles showed that there exists a typical or "normal" pattern for each muscle which most uninjured and some injured subjects exhibit as well as several atypical patterns which mostly injured subjects exhibit, and that the atypical patterns are much more evident at fast walking speed. The characteristics of atypical patterns with respect to normal include time shifts in the peak of major phases of activity, the absence of a second phase of activity, and the existence of additional phases of activity. Synergy analysis showed that if one muscle has an atypical pattern, then several do; i.e., ACL injury induces major changes in the control strategy of the knee. The implications are that for rehabilitation programs one must focus on the training and strengthening of more than one muscle, and that for reconstructive procedures the changes in mechanics of the joint can possibly induce a significant change in its control strategy.