The Effects of Delays in Diagnosis and Surgical Reconstruction of ACL Tears in Skeletally Immature Individuals on Subsequent Meniscal and Chondral Injury.

BACKGROUND: Although studies have shown increased rates of chondral injury with delayed surgical treatment of pediatric anterior cruciate ligament (ACL) injuries, it is unknown if this is related to a delay in diagnosis and appropriate activity restrictions. The purpose of this study was to determine if the time from injury to diagnosis, time from diagnosis to reconstruction, and preoperative activity level correlate with the degree of cartilage injury seen intraoperatively. METHODS: A retrospective review of skeletally immature patients who underwent ACL reconstruction was performed. Patients were stratified based on the time from injury to diagnosis (≤6 vs. >6 wk), diagnosis to surgery (≤6 vs. >6 wk), and injury to surgery (≤12 vs. >12 wk). Weight-bearing status, brace usage, athletic participation, and meniscus tears were characterized as binary variables. Articular cartilage injury was graded on a scale of 0 to 3. Differences between groups were analyzed using the χ test. RESULTS: In total, 91 subjects with mean age of 13 years (range, 9 to 16 y) were included. In total, 71% were diagnosed within 6 weeks of injury and 40% underwent surgery within 6 weeks of diagnosis. No differences were found in the presence of medial or lateral meniscus tears or the grade of articular cartilage damage when groups were analyzed by time from injury to diagnosis, diagnosis to surgery, and injury to surgery (P>0.05 in all cases). When stratified by weight-bearing status, brace status, and athletic activity, there were no significant differences between groups for meniscal tears or cartilage injury in any compartment (P>0.05). CONCLUSIONS: Diagnosis of ACL rupture within 6 weeks of injury and surgical reconstruction within 6 weeks of diagnosis or 12 weeks of injury do not appear to affect the rate of cartilage injury in skeletally immature patients. Weight-bearing status, brace use, and participation in athletic activities between the time of injury and diagnosis also did not impact the rate of intra-articular injury following ACL tear. LEVEL OF EVIDENCE: Level IV.

Restricted Hip Rotation Is Correlated With an Increased Risk for Anterior Cruciate Ligament Injury.

PURPOSE: The primary purpose was to compare ipsilateral hip internal rotation (IR) in male and female athletes with or without an anterior cruciate ligament (ACL) tear. A secondary purpose was to compare radiographic markers of femoroacetabular impingement (FAI) in patients with or without an ACL tear. METHODS: In this prospective case-control study, based on a power analysis, a convenience sample of 25 ACL-injured and 25 control patients matched by age and gender were examined over 14 months. The ACL injury group included preoperative patients 12-40 years old with an ACL rupture within the previous 3 months with no prior lower extremity injuries, ligamentous laxity, or arthralgias. Controls included patients presenting with an upper extremity complaint with no history of knee injury. In the outpatient clinic, hip axial rotation range of motion was measured with a goniometer on physical examination and hip radiographs were evaluated for morphologic variations consistent with FAI. Univariate analysis of variance was used to examine differences between groups. RESULTS: Each group had 13 males and 12 females, average ages of 22.8 ± 7.2 years (ACL group) versus 24.5 ± 7.9 years (controls; P = .439). The average sum of hip rotation (internal plus external) in patients with an ACL tear was 60.3 ± 12.4° compared with 72.6 ± 17.2° in controls (P = .006). ACL-injured patients had decreased hip IR compared with controls, with respective mean measurements of 23.4 ± 7.6° versus 30.4 ± 10.4° (P = .009). For every 10° increase in hip IR, the odds of having an ACL tear decreased by a factor of 0.419 (P = .015). CONCLUSIONS: Risk of ACL injury is associated with restricted hip IR, and as hip IR increases, the odds of having an ACL tear decreases. In addition, ACL injury is associated with FAI in a generalized population of male and female athletes, although causality cannot be determined and most ACL-injured patients do not exhibit hip complaints. LEVEL OF EVIDENCE: Level II, prognostic, prospective cohort study.

In vivo structural and cellular remodeling of engineered bone-ligament-bone constructs used for anterior cruciate ligament reconstruction in sheep.

Anterior cruciate ligament (ACL) ruptures rank among the most prevalent and costly sports-related injuries. Current tendon grafts used for ACL reconstruction are limited by suboptimal biomechanical properties. We have addressed these issues by engineering multiphasic bone-ligament-bone (BLB) constructs that develop structural and mechanical properties similar to native ACL. The purpose of this study was to examine the acute remodeling process that occurs as the BLB grafts advance toward the adult ligament phenotype in vivo. Thus, we implanted BLB constructs fabricated from male cells into female host sheep and allowed 3, 7, 14, or 28 days (n = 4 at each time point) for recovery. To address whether or not graft-derived cells were even necessary, a subset of BLB constructs (n = 3) were acellularized, implanted, and allowed 28 days for recovery. At each recovery time point, the following histological analyses were performed: picrosirius red staining to assess collagen alignment and immunohistochemistry to assess both graft development and host immune response. Polymerase chain reaction (PCR) analysis, performed on every explanted BLB, was used to detect the presence of graft-derived male cells remaining in the constructs and/or migration into surrounding host tissue. The analysis of the PCR and histology samples revealed a rapid migration of host-derived macrophages and neutrophils into the graft at 3 days, followed by increased collagen density and alignment, vascularization, innervation, and near complete repopulation of the graft with host cells within 28 days. This study provides a greater understanding of the processes of ligament regeneration in our BLB constructs as they remodel toward the adult ligament phenotype.

Early Cartilage Changes After Anterior Cruciate Ligament Injury: Evaluation With Imaging and Serum Biomarkers-A Pilot Study.

PURPOSE: To determine if magnetic resonance imaging markers of cartilage matrix and morphology and circulating serum biomarkers of inflammation and matrix degradation differ over time in patients with anterior cruciate ligament (ACL) injury and bone marrow edema lesions (BMELs) when compared with matched control subjects. METHODS: We performed a case-control study, in which 11 ACL-injured subjects scheduled to undergo reconstruction and 11 matched control subjects were scheduled for testing. Participants were selected for the ACL reconstruction (ACLR) group if they injured their ACL while participating in sports, were aged 14 to 30 years, had 1 or more BMELs, and were scheduled to undergo bone-patellar tendon-bone ACLR. Testing required patients to undergo magnetic resonance imaging for measurement of T2 relaxation times in standardized regions of interest over the medial and lateral tibial plateaus and femoral condyles and have blood drawn for measurement of cartilage oligomeric matrix protein (COMP) and C-reactive protein levels before ligament reconstruction and 1 year after surgery. RESULTS: ACL patients had prolonged T2 relaxation times, indicative of cartilage matrix degradation, in the superficial central lateral tibial plateau (P = .02) and deep medial tibial plateau when compared with control subjects (P = .0001). Prolonged T2 relaxation times were also noted over the lateral femoral condyle at baseline for ACL patients compared with control subjects (P = .001), but the differences resolved by 1 year (P = .98). Circulating serum COMP levels were greater in ACL patients (233.23 ± 88.26 ng/mL) compared with control subjects (169.05 ± 64.53 ng/mL, P = .05). CONCLUSIONS: T2 mapping showed prolonged relaxation times in the lateral compartment of the knee in ACLR patients with lateral BMELs. Furthermore, prolonged T2 relaxation times were apparent in the medial compartment of the knee in ACL-injured patients where bone marrow lesions were not present. Higher serum COMP levels were present in ACL-injured subjects when compared with control subjects. LEVEL OF EVIDENCE: Level II, prospective case-control study.

Restriction in hip internal rotation is associated with an increased risk of ACL injury.

PURPOSE: Evidence suggests that femoroacetabular impingement (FAI) in athletes may increase the risk of anterior cruciate ligament (ACL) injury. This study correlates ACL injury with hip range of motion in a consecutive series of elite, contact athletes and tests the hypothesis that a restriction in the available hip axial rotation in a dynamic in silico model of a simulated pivot landing would increase ACL strain and the risk of ACL rupture. METHODS: Three hundred and twenty-four football athletes attending the 2012 NFL National Invitational Camp were examined. Hip range of internal rotation was measured and correlated with a history of ACL injury and surgical repair. An in silico biomechanical model was used to study the effect of FAI on the peak relative ACL strain developed during a simulated pivot landing. RESULTS: The in vivo results demonstrated that a reduction in internal rotation of the left hip was associated with a statistically significant increased odds of ACL injury in the ipsilateral or contralateral knee (OR 0.95, p = 0.0001 and p < 0.0001, respectively). A post-estimation calculation of odds ratio for ACL injury based on deficiency in hip internal rotation demonstrated that a 30-degree reduction in left hip internal rotation was associated with 4.06 and 5.29 times greater odds of ACL injury in the ipsilateral and contralateral limbs, respectively. The in silico model demonstrated that FAI systematically increased the peak ACL strain predicted during the pivot landing. CONCLUSION: FAI may be associated with ACL injury because of the increased resistance to femoral internal axial rotation during a dynamic maneuver such as a pivot landing. This insight may lead to better interventions to prevent ACL injury and improved understanding of ACL reconstruction failure. LEVEL OF EVIDENCE: Cohort study, Level IV.

Does concomitant meniscectomy or meniscal repair affect the recovery of quadriceps function post-ACL reconstruction?

PURPOSE: The purpose of this study was to determine the effect of concomitant meniscal surgery on the recovery of quadriceps activation and strength at a time when individuals return to sport following anterior cruciate ligament (ACL) reconstruction. METHODS: Forty-six individuals that were cleared for participation following ACL reconstruction were invited to participate in this study. Participants were placed into groups according to surgical reports (ACL-only, n = 24; meniscal repair, n = 12; meniscectomy, n = 10). Quadriceps strength was quantified using isokinetic and isometric measures. Isokinetic strength was collected at 60°/s in concentric mode. Isometric strength was collected at 90° of knee flexion. Quadriceps activation was assessed using the burst superimposition technique and quantified via the central activation ratio. One-way ANOVAs were utilized to detect whether differences existed in quadriceps activation and strength between groups. Where appropriate, post hoc Bonferroni multiple comparison procedures were used. RESULTS: Quadriceps activation (P = n.s.) and strength (isokinetic: P = n.s.; isometric: P = n.s.) were not different between groups. CONCLUSION: Concomitant meniscectomy or meniscal repair did not affect the recovery of quadriceps activation and strength at a time when individuals return to sport following ACL reconstruction. Though group differences in quadriceps function were not detected, all participants demonstrated levels of quadriceps activation failure that are below healthy individuals at a time when they were returned to sport. Given that persistent quadriceps activation failure is detrimental to knee function, rehabilitation protocols that target quadriceps activation failure should be developed and employed post-reconstruction.

Is the all-arthroscopic tibial inlay double-bundle PCL reconstruction a viable option in multiligament knee injuries?

BACKGROUND: All-arthroscopic tibial inlay double-bundle (DB) posterior cruciate ligament (PCL) reconstruction avoids an open dissection and the "killer turn" while maintaining the advantage of an anatomic graft. However, clinical data on the viability of this surgical technique in multiligamentous knee injuries are lacking. QUESTIONS/PURPOSES: At greater than 2 years of followup, we evaluated (1) validated outcomes scores; (2) range of motion; and (3) side-to-side stability on PCL stress radiographs of a small group of patients who underwent all-arthroscopic tibial inlay DB PCL reconstruction in multiligamentous knee injuries, either shortly after injury or late. METHODS: All patients sustaining an operative multiligamentous knee injury between August 2007 and March 2009 underwent PCL reconstruction with the all-arthroscopic tibial inlay DB PCL reconstruction. Twelve patients sustained such injuries and were reconstructed during the study period and all 12 returned for followup with a minimum of 2 years (mean 3 ± 0.8 years). There were nine males and three females, with a mean age of 30 years; four patients had a subacute reconstruction (≥ 3 weeks, but < 3 months), and eight patients had chronic reconstructions (> 3 months). Mean time from injury to PCL reconstruction was 7 ± 12 months. Demographics, ROM, outcome scores (Lysholm and International Knee Documentation Committee [IKDC] scores), and PCL stress views were obtained. RESULTS: At final followup, mean Lysholm and IKDC subjective scores were 79 ± 16 and 72 ± 19, respectively. IKDC objective scores included eight nearly normal knees, three abnormal knees, and one severely abnormal knee. Mean flexion and extension losses compared with the contralateral were 10 ± 9 and 1 ± 2, respectively. Mean ± SD final side-to-side difference on PCL stress radiographs was 5 ± 3 mm. CONCLUSIONS: The clinical and radiographic results of the all-arthroscopic tibial inlay DB PCL reconstruction appear comparable to the same technique in isolated PCL injuries and, based on similar published case series, comparable to results of multiligamentous knee reconstructions using other PCL reconstruction techniques. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Structural and functional analysis of the semitendinosus tendon after harvest for soft tissue reconstructive procedures: a dynamic ultrasonographic study.

PURPOSE: To assess the potential for regeneration of the hamstring tendons after harvesting for various soft tissue reconstructive procedures, this study uses dynamic, high-resolution ultrasound to evaluate the presence of any tissue in the harvest gap and to characterize tissue functionality. METHODS: Patients who underwent ACL reconstruction using ipsilateral hamstring autograft were identified in the database of a single surgeon. Dynamic 12-MHz sonographic imaging was used to evaluate the ipsilateral and contralateral (control) semitendinosus tendons from their insertion sites to proximal muscle bellies. The presence or absence and echogenicity of tissue in the harvest defect, tissue appearance, degree of retraction of the proximal tendon stump, thickness of gap tissue, and motion of the proximal tendon stump were recorded. Data were analysed with Wilcoxon-Mann-Whitney, sign or binomial tests, with significance of P < 0.05. RESULTS: Eighteen knees in 15 patients (aged 17-51 years) were studied. The proximal amputated stump was retracted an average of 9.0 ± 7.6 cm (range, 0-18 cm; P = 0.0063). With dynamic testing, 9 of 15 knees demonstrated decreased excursion of the proximal tendon stump when compared to the native, contralateral muscle-tendon unit (P = 0.0039). Tissue was detected in the harvest gap in nine knees, five of which had harvest gap tissue with a disorganized appearance compared to the native tendon (P < 0.0001). Six of these nine knees had tissue in the gap demonstrating either less or no excursion with active knee flexion when compared to the native, contralateral side (P = 0.0313). CONCLUSIONS: The presence of tissue in the harvest gap after ACL reconstruction is variable. When tissue is present, there is proximal retraction of the musculotendinous junction and disorganized appearance of the tissue that does not demonstrate normal excursion or physiological function similar to the native muscle-tendon unit. LEVEL OF EVIDENCE: Case series, Level IV.

Loading mechanisms of the anterior cruciate ligament.

This review identifies the three-dimensional knee loads that have the highest risk of injuring the anterior cruciate ligament (ACL) in the athlete. It is the combination of the muscular resistance to a large knee flexion moment, an external reaction force generating knee compression, an internal tibial torque, and a knee abduction moment during a single-leg athletic manoeuvre such as landing from a jump, abruptly changing direction, or rapidly decelerating that results in the greatest ACL loads. While there is consensus that an anterior tibial shear force is the primary ACL loading mechanism, controversy exists regarding the secondary order of importance of transverse-plane and frontal-plane loading in ACL injury scenarios. Large knee compression forces combined with a posteriorly and inferiorly sloped tibial plateau, especially the lateral plateau-an important ACL injury risk factor-causes anterior tibial translation and internal tibial rotation, which increases ACL loading. Furthermore, while the ACL can fail under a single supramaximal loading cycle, recent evidence shows that it can also fail following repeated submaximal loading cycles due to microdamage accumulating in the ligament with each cycle. This challenges the existing dogma that non-contact ACL injuries are predominantly due to a single manoeuvre that catastrophically overloads the ACL.

Relationship Between Lateral Tibial Posterior Slope and Tibiofemoral Kinematics During Simulated Jump Landings in Male Cadaveric Knees.

Background: It is not known mechanistically whether a steeper lateral posterior tibial slope (LTS) leads to an increase in anterior tibial translation (ATT) as well as internal tibial rotation (ITR) during a given jump landing. Hypothesis: A steeper LTS will result in increased ATT and ITR during simulated jump landings when applying knee compression, flexion, and internal tibial torque of increasing severity. Study Design: Descriptive laboratory study. Methods: Seven pairs of cadaveric knees were harvested from young male adult donors (mean ± SD; age, 25.71 ± 5.53 years; weight, 71.51 ± 4.81 kg). The LTS of each knee was measured by a blinded observer from 3-T magnetic resonance images. Two sets of 25 impact trials of ∼700 N (1× body weight [BW] ±10%) followed by 2 sets of 25 trials of 1400 N (2× BW ±10%) were applied to a randomly selected knee of each pair. Similarly, on the contralateral knee, 2 sets of 25 impact trials of ∼1800 N (2.5× BW ±10%) followed by 2 sets of 25 trials of ∼2100 N (3× BW ±10%) were applied. Three-dimensional knee kinematics, including ATT and ITR, were measured at 400 Hz using optoelectronic motion capture. Two-factor linear mixed effect models were used to determine the relationship of LTS to ATT and ITR as impact loading increased. Results: As LTS increased, so did ATT and ITR during increasingly severe landings. LTS had an increasing effect on ATT (coefficient, 0.50; 95% CI, 0.29-0.71) relative to impact force (coefficient, 0.52; 95% CI, 0.50-0.53). ITR was proportional to LTS (coefficient, 1.36; 95% CI, 0.80-1.93) under increasing impact force (coefficient, 0.49; 95% CI, 0.47-0.52). For steeper LTS, the increase in ITR was proportionally greater than the increase in ATT. Conclusion: In male knee specimens, a steeper LTS significantly increased ATT and ITR during jump landings. Clinical Relevance: Increases in ITR and ATT during jump landings lead to increased strain on the anterior cruciate ligament and are therefore associated with greater risk of ligament failure.

Levels of ACL-straining activities increased in the six months prior to non-contact ACL injury in a retrospective survey: evidence consistent with ACL fatigue failure.

Introduction: Recent evidence has emerged suggesting that a non-contact anterior cruciate ligament (ACL) tear can result from repetitive submaximal loading of the ligament. In other words, when the intensity of ACL-straining athletic activities is increased too rapidly, microdamage can accumulate in the ligament beyond the rate at which it can be repaired, thereby leading to material fatigue in the ligament and its eventual failure. The objective of this survey-based exploratory study was to retrospectively determine whether the levels of various athletic activities performed by ACL-injured patients significantly changed during the 6 months before injury. Methods: Forty-eight ACL-injured patients completed a survey to characterize their participation in various activities (weightlifting, sport-specific drills, running, jumping, cutting, pivoting/twisting, and decelerating) at three timepoints (1 week, 3 months, 6 months) prior to ACL injury. Activity scores, which summarized the frequency and intensity of each activity, were calculated for each patient at each time interval. A series of linear mixed-effects regression models was used to test whether there was a significant change in levels of the various activities in the 6-month period leading up to ACL injury. Results: Patients who sustained a non-contact ACL injury markedly increased their sport-specific drills activity levels in the time leading up to injury (p = 0.098), while those patients who sustained a contact ACL injury exhibited no change in this activity during the same time period (p = 0.829). Levels of running, jumping, cutting, pivoting/twisting, and decelerating increased for non-contact ACL-injured patients but decreased for contact ACL-injured patients, though not significantly (p values > 0.10). Weightlifting activity significantly decreased leading up to injury among contact ACL-injured patients (p = 0.002). Discussion: We conclude that levels of ACL-straining athletic activities or maneuvers in non-contact ACL-injured patients markedly increased in the 6 months leading up to their injury, providing evidence that changing levels of certain activities or maneuvers may play a role in ACL injury risk. This warrants further investigation of the hypothesis that too rapid an increase in activities or maneuvers known to place large loads on the ACL can cause microdamage to accumulate in the ligament, thereby leading to failure.

An Adolescent Murine In Vivo Anterior Cruciate Ligament Overuse Injury Model.

BACKGROUND: Overuse ligament and tendon injuries are prevalent among recreational and competitive adolescent athletes. In vitro studies of the ligament and tendon suggest that mechanical overuse musculoskeletal injuries begin with collagen triple-helix unraveling, leading to collagen laxity and matrix damage. However, there are little in vivo data concerning this mechanism or the physiomechanical response to collagen disruption, particularly regarding the anterior cruciate ligament (ACL). PURPOSE: To develop and validate a novel in vivo animal model for investigating the physiomechanical response to ACL collagen matrix damage accumulation and propagation in the ACL midsubstance, fibrocartilaginous entheses, and subchondral bone. STUDY DESIGN: Controlled laboratory study. METHODS: C57BL/6J adolescent inbred mice underwent 3 moderate to strenuous ACL fatigue loading sessions with a 72-hour recovery between sessions. Before each session, randomly selected subsets of mice (n = 12) were euthanized for quantifying collagen matrix damage (percent collagen unraveling) and ACL mechanics (strength and stiffness). This enabled the quasi-longitudinal assessment of collagen matrix damage accrual and whole tissue mechanical property changes across fatigue sessions. Additionally, all cyclic loading data were quantified to evaluate changes in knee mechanics (stiffness and hysteresis) across fatigue sessions. RESULTS: Moderate to strenuous fatigue loading across 3 sessions led to a 24% weaker (P = .07) and 35% less stiff (P < .01) ACL compared with nonloaded controls. The unraveled collagen densities within the fatigued ACL and entheseal matrices after the second and third sessions were 38% (P < .01) and 15% (P = .02) higher compared with the nonloaded controls. CONCLUSION: This study confirmed the hypothesis that in vivo ACL collagen matrix damage increases with tissue fatigue sessions, adversely impacting ACL mechanical properties. Moreover, the in vivo ACL findings were consistent with in vitro overloading research in humans. CLINICAL RELEVANCE: The outcomes from this study support the use of this model for investigating ACL overuse injuries.

MRI Findings Associated With Anterior Cruciate Ligament Tears in National Football League Athletes.

Background: Anterior cruciate ligament (ACL) tears are a high-frequency injury requiring a lengthy recovery in professional American football players. Concomitant pathology associated with ACL tears as identified on magnetic resonance imaging (MRI) is not well understood in these athletes. Purpose: To describe the MRI findings of concomitant injuries associated with ACL tears among athletes in the National Football League (NFL). Study Design: Cross-sectional study; Level of evidence, 3. Methods: Of 314 ACL injuries in NFL athletes from 2015 through 2019, 191 complete MRI scans from the time of primary ACL injury were identified and reviewed by 2 fellowship-trained musculoskeletal radiologists. Data were collected on ACL tear type and location, as well as presence and location of bone bruises, meniscal tears, articular cartilage pathology, and concomitant ligament pathology. Mechanism data from video review were linked with imaging data to assess association between injury mechanism (contact vs noncontact) and presence of concomitant pathology. Results: Bone bruises were evident in 94.8% of ACL tears in this cohort, most often in the lateral tibial plateau (81%). Meniscal, additional ligamentous, and/or cartilage injury was present in 89% of these knees. Meniscal tears were present in 70% of knees, lateral (59%) more than medial (41%). Additional ligamentous injury was present in 71% of all MRI scans, more often a grade 1/2 sprain (67%) rather than a grade 3 tear (33%), and most often involving the medial collateral ligament (MCL) (57%) and least often the posterior cruciate ligament (10%). Chondral damage was evident in 49% of all MRI scans, with ≥1 full-thickness defect in 25% of all MRI scans, most often lateral. Most (79%) ACL tears did not involve direct contact to the injured lower extremity. Direct contact injuries (21%) were more likely to have a concomitant MCL tear and/or medial patellofemoral ligament injury and less likely to have a medial meniscal tear. Conclusion: ACL tears were rarely isolated injuries in this cohort of professional American football athletes. Bone bruises were almost always present, and additional meniscal, ligamentous, and chondral injuries were also common. MRI findings varied by injury mechanism.

Acute Bone Loss and Infrapatellar Fat Pad Fibrosis in the Knee After an In Vivo ACL Injury in Adolescent Mice.

BACKGROUND: Young patients are 6 times more likely than adults to have a primary anterior cruciate ligament (ACL) graft failure. Biological factors (ie, tunnel osteolysis) may account for up to a third of these failures. Previous evaluations of patient ACL explants indicated significant bone loss within the entheseal regions. However, it remains unknown if the degree of bone loss within the ACL insertion regions, wherein ACL grafts are fixated, exceeds that of the femoral and tibial condylar bone. HYPOTHESIS: Bone loss in the mineralized matrices of the femoral and tibial ACL entheses is distinct from that clinically reported across the whole knee after injury. STUDY DESIGN: Controlled laboratory study. METHODS: We developed a clinically relevant in vivo mouse ACL injury model to cross-sectionally track the morphological and physiological postinjury changes within the ACL, femoral and tibial entheses, synovial joint space, and load-bearing epiphyseal cortical and trabecular bone components of the knee joint. Right ACLs of 10-week-old C57BL/6J female mice (N = 75) were injured in vivo with the contralateral ACLs serving as controls. Mice were euthanized at 1, 3, 7, 14, or 28 days after injury (n = 12/cohort). Downstream analyses included volumetric cortical and trabecular bone analyses and histopathologic assessments of the knee joint after injury. Gait analyses across all time points were also performed (n = 15 mice). RESULTS: The majority of the ACL injuries in mice were partial tears. The femoral and tibial cortical bone volumes were 39% and 32% lower, respectively, at 28 days after injury than those of the uninjured contralateral knees (P < .01). Trabecular bone measures demonstrated little difference between injured and control knees after injury. Across all bone measures, bone loss was similar between the injured knee condyles and ACL entheses. There was also significant inflammatory activity within the knee after injury. By 7 days after injury, synovitis and fibrosis were sigificantly elevated in the injured knee compared with the controls (P < .01), which corresponded with significantly higher osteoclast activity in bone at this time point compared with the controls. This inflammatory response signficantly persisted throughout the duration of the study (P < .01). The hindlimb gait after injury deviated from normal, but mice habitually loaded their injured knee throughout the study. CONCLUSION: Bone loss was acute and persisted for 4 weeks after injury in mice. However, the authors' hypothesis was not confirmed, as bone quality was not significantly lower in the entheses compared with the condylar bone regions after injury. With relatively normal hindlimb loading but a significant physiological response after injury, bone loss in this model may be driven by inflammation. CLINICAL RELEVANCE: There is persistent bone resorption and fibrotic tissue development after injury that is not resolved. Inflammatory and catabolic activity may have a significant role in the postinjury decline of bone quality in the knee.

Fatigue-driven compliance increase and collagen unravelling in mechanically tested anterior cruciate ligament.

Approximately 300,000 anterior cruciate ligament (ACL) tears occur annually in the United States, half of which lead to the onset of knee osteoarthritis within 10 years of injury. Repetitive loading is known to result in fatigue damage of both ligament and tendon in the form of collagen unravelling, which can lead to structural failure. However, the relationship between tissue's structural, compositional, and mechanical changes are poorly understood. Herein we show that repetitive submaximal loading of cadaver knees causes an increase in co-localised induction of collagen unravelling and tissue compliance, especially in regions of greater mineralisation at the ACL femoral enthesis. Upon 100 cycles of 4× bodyweight knee loading, the ACL exhibited greater unravelled collagen in highly mineralized regions across varying levels of stiffness domains as compared to unloaded controls. A decrease in the total area of the most rigid domain, and an increase in the total area of the most compliant domain was also found. The results highlight fatigue-driven changes in both protein structure and mechanics in the more mineralized regions of the ACL enthesis, a known site of clinical ACL failure. The results provide a starting point for designing studies to limit ligament overuse injury.

Functional Resistance Training Improves Thigh Muscle Strength after ACL Reconstruction: A Randomized Clinical Trial.

PURPOSE: Quadriceps weakness is common after anterior cruciate ligament (ACL) reconstruction, resulting in prolonged disability and increased risk for reinjury and osteoarthritis. Functional resistance training (FRT) combines resistance training with task-specific training and may prove beneficial in restoring quadriceps strength. The primary purpose of this study was to determine if a walking-specific FRT program (e.g., resisted walking) improves knee strength in individuals after ACL reconstruction. METHODS: Thirty participants were randomized into one of three groups: 1) FRT with a customized knee BRACE applied to the ACL leg, 2) FRT with elastic BAND tethered to the ankle of the ACL leg, or 3) a TARGET MATCH condition where no resistance was externally applied. Participants in all groups received training while walking on a treadmill 2-3 times per week for 8 wk. Isometric knee extension and flexion strength were measured before the start of the intervention, after the intervention (POST), and 8 wk after intervention completion (POST-2). RESULTS: The BRACE group had greater knee extensor strength compared with the TARGET MATCH group at POST and POST-2 ( P < 0.05). The BRACE group had greater knee flexor strength than the TARGET MATCH group at POST and POST-2 ( P < 0.05) and the BAND group at POST ( P < 0.05). CONCLUSIONS: FRT applied via a customized knee brace results in improvements in knee extensor and flexor strength after ACL reconstruction. FRT is a beneficial adjuvant to ACL rehabilitation and leads to better strength compared with standard of care.

The Lateral Femoral Condyle Index Is Not a Risk Factor for Primary Noncontact Anterior Cruciate Ligament Injury.

BACKGROUND: The lateral femoral condyle index (LFCI)-a recently developed measure of the sphericity of the lateral femoral condyle-was reported to be a risk factor for anterior cruciate ligament (ACL) injury. However, issues have been raised regarding how the index was measured and regarding the patient group and the knee in which it was measured. PURPOSE: To investigate the association between the LFCI and the risk of sustaining a primary, noncontact ACL injury, and to examine whether this association was moderated by the posterior-inferior-directed slope of the lateral tibial plateau. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A secondary analysis was conducted of deidentified magnetic resonance images of the uninjured knees of 86 athletes with ACL injury and the corresponding knees of 86 control athletes, matched for sports team, sex, and age. From those images, we measured the LFCI and the posterior-inferior-directed slope of the middle region articular cartilage surface of the tibial plateau's lateral compartment. Conditional logistic regressions were performed to determine whether the LFCI was significantly associated with ACL injury risk and whether the lateral tibial compartment middle cartilage slope moderated this association. Data were analyzed for female and male participants separately as well as for both groups combined. RESULTS: The LFCI was not found to be significantly associated with experiencing a primary, noncontact ACL injury for all analyses. The lateral tibial slope measure was not found to moderate the association between the LFCI and ACL injury. A conditional logistic regression analysis using the LFCI data of the injured knees, instead of the uninjured knees, of the participants with ACL injury revealed that the LFCI was significantly associated with ACL injury. CONCLUSION: In this population of athletically active female and male participants, the LFCI was not found to be a risk factor for noncontact ACL injury, regardless of the geometric features of the lateral tibial slope.

Endurance running during late murine adolescence results in a stronger anterior cruciate ligament and flatter posterior tibial slopes compared to controls.

BACKGROUND: Anterior cruciate ligament (ACL) injury rates continue to rise among youth involved in recreational and competitive athletics, requiring a better understanding of how the knee structurally and mechanically responds to activity during musculoskeletal growth. Little is understood about how anatomical risk factors for ACL injury (e.g., small ACL size, narrow intercondylar notch, and steep posterior tibial slope) develop and respond to increased physical activity throughout growth. We hypothesized that the ACL-complex of mice engaged in moderate to strenuous physical activity (i.e., endurance running) throughout late adolescence and young adulthood would positively functionally adapt to repetitive load perturbations. METHODS: Female C57BL6/J mice (8 weeks of age) were either provided free access to a standard cage wheel with added resistance (n = 18) or normal cage activity (n = 18), for a duration of 4 weeks. Daily distance ran, weekly body and food weights, and pre- and post-study body composition measures were recorded. At study completion, muscle weights, three-dimensional knee morphology, ACL cross-sectional area, and ACL mechanical properties of runners and nonrunners were quantified. Statistical comparisons between runners and nonrunners were assessed using a two-way analysis of variance and a Tukey multiple comparisons test, with body weight included as a covariate. RESULTS: Runners had larger quadriceps (p = 0.02) and gastrocnemius (p = 0.05) muscles, but smaller hamstring (p = 0.05) muscles, compared to nonrunners. Though there was no significant difference in ACL size (p = 0.24), it was 13% stronger in runners (p = 0.03). Additionally, both the posterior medial and lateral tibial slopes were 1.2 to 2.2 degrees flatter than those of nonrunners (p < 0.01). CONCLUSIONS: Positive functional adaptations of the knee joint to moderate to strenuous exercise in inbred mice offers hope that that some anatomical risk factors for ACL injury may be reduced through habitual physical activity. However, confirmation that a similar response to loading occurs in humans is needed.

State of the mineralized tissue comprising the femoral ACL enthesis in young women with an ACL failure.

Despite poor graft integration among some patients that undergo an anterior cruciate ligament (ACL) reconstruction, there has been little consideration of the bone quality into which the ACL femoral tunnel is drilled and the graft is placed. Bone mineral density of the knee decreases following ACL injury. However, trabecular and cortical architecture differences between injured and non-injured femoral ACL entheses have not been reported. We hypothesize that injured femoral ACL entheses will show significantly less cortical and trabecular mass compared with non-injured controls. Femoral ACL enthesis explants from 54 female patients (13-25 years) were collected during ACL reconstructive surgery. Control explants (n = 12) were collected from seven donors (18-36 years). Injured (I) femoral explants differed from those of non-injured (NI) controls with significantly less (p ≤ 0.001) cortical volumetric bone mineral density (vBMD) (NI: 736.1-867.6 mg/cm3 ; I: 451.2-891.9 mg/cm3 ), relative bone volume (BV/TV) (NI: 0.674-0.867; I: 0.401-0.792) and porosity (Ct.Po) (NI: 0.133-0.326; I: 0.209-0.600). Injured explants showed significantly less trabecular vBMD (p = 0.013) but not trabecular BV/TV (p = 0.314), thickness (p = 0.412), or separation (p = 0.828). We found significantly less cortical bone within injured femoral entheses compared to NI controls. Lower cortical and trabecular bone mass within patient femoral ACL entheses may help explain poor ACL graft osseointegration outcomes in the young and may be a contributor to the osteolytic phenomenon that often occurs within the graft tunnel following ACL reconstruction.

Anterior cruciate ligament microfatigue damage detected by collagen autofluorescence in situ.

PURPOSE: Certain types of repetitive sub-maximal knee loading cause microfatigue damage in the human anterior cruciate ligament (ACL) that can accumulate to produce macroscopic tissue failure. However, monitoring the progression of that ACL microfatigue damage as a function of loading cycles has not been reported. To explore the fatigue process, a confocal laser endomicroscope (CLEM) was employed to capture sub-micron resolution fluorescence images of the tissue in situ. The goal of this study was to quantify the in situ changes in ACL autofluorescence (AF) signal intensity and collagen microstructure as a function of the number of loading cycles. METHODS: Three paired and four single cadaveric knees were subjected to a repeated 4 times bodyweight landing maneuver known to strain the ACL. The paired knees were used to compare the development of ACL microfatigue damage on the loaded knee after 100 consecutive loading cycles, relative to the contralateral unloaded control knee, through second harmonic generation (SHG) and AF imaging using confocal microscopy (CM). The four single knees were used for monitoring progressive ACL microfatigue damage development by AF imaging using CLEM. RESULTS: The loaded knees from each pair exhibited a statistically significant increase in AF signal intensity and decrease in SHG signal intensity as compared to the contralateral control knees. Additionally, the anisotropy of the collagen fibers in the loaded knees increased as indicated by the reduced coherency coefficient. Two out of the four single knee ACLs failed during fatigue loading, and they exhibited an order of magnitude higher increase in autofluorescence intensity per loading cycle as compared to the intact knees. Of the three regions of the ACL - proximal, midsubstance and distal - the proximal region of ACL fibers exhibited the highest AF intensity change and anisotropy of fibers. CONCLUSIONS: CLEM can capture changes in ACL AF and collagen microstructures in situ during and after microfatigue damage development. Results suggest a large increase in AF may occur in the final few cycles immediately prior to or at failure, representing a greater plastic deformation of the tissue. This reinforces the argument that existing microfatigue damage can accumulate to induce bulk mechanical failure in ACL injuries. The variation in fiber organization changes in the ACL regions with application of load is consistent with the known differences in loading distribution at the ACL femoral enthesis.