An efficient R1ρ dispersion imaging method for human knee cartilage using constant magnetization prepared turbo-FLASH.

This work aimed to develop an efficient R1ρ dispersion imaging method for clinical studies of human knee cartilage at 3 T. Eight constant magnetizations (Mprep ) were prepared by tailoring both the duration and amplitude (ω1 ) of a fully refocused spin-lock preparation pulse. The limited Mprep dynamic range was expanded by the measure, equivalent to that with ω1 = ∞, from the magic angle location in the deep femoral cartilage. The developed protocol with Mprep = 60% was demonstrated on one subject's bilateral and two subjects' unilateral asymptomatic knees. The repeatability of the proposed protocol was estimated by two repeated scans with a three-month gap for the last two subjects. The synthetic R1ρ and R2 derived from R1ρ dispersions were compared with the published references using state-of-the-art R1ρ and R2 mapping (MAPSS). The proposed protocol demonstrated good (<5%) repeatability quantified by the intra- and intersubject coefficients of variation in the femoral and tibial cartilage. The synthetic R1ρ (1/s) and the references were comparable in the femoral (23.0 ± 5.3 versus 24.1 ± 3.8, P = 0.67) and the tibial (29.1 ± 8.8 versus 27.1 ± 5.1, P = 0.62), but not the patellar (16.5 ± 4.9 versus 22.7 ± 1.6, P < 0.01) cartilage. The same trends were also observed for the current and the previous R2 . In conclusion, the developed R1ρ dispersion imaging scheme has been revealed to be not only efficient but also robust for clinical studies of human knee cartilage at 3 T.

Impact of different physical activity types on knee joint structural degeneration assessed with 3-T MRI in overweight and obese subjects: data from the osteoarthritis initiative.

OBJECTIVE: To assess the impact of different types of physical activity types on longitudinal knee joint structural changes over 48 months in overweight and obese subjects. MATERIALS AND METHODS: We included 415 subjects with a BMI ≥ 25 kg/m2, Kellgren-Lawrence scores ≤ 3 at baseline and Whole-Organ Magnetic Resonance Imaging Score (WORMS) scores available from the Osteoarthritis Initiative cohort. Regular self-reported participation in six physical activity types was assessed: ball sports, bicycling, jogging/running, elliptical-trainer, racquet sports, and swimming. Moreover, they were classified into high- and low-impact physical activity groups. Evaluation of structural knee abnormalities was performed using WORMS obtained by two independent observers blinded to the subjects' physical activity and time point. Linear regression models were used to assess the associations between participation in different physical activity types and changes in WORMS. RESULTS: No significant differences in epidemiological data were found between the groups except for gender composition, and there were no significant differences in baseline WORMS. In the cohort as a whole and most exercise groups overall WORMS significantly increased during the observational period. Highest increases compared to the remainder of the group were found in the high impact group (increase in WORMS 4.65; [95% CI] [3.94,5.35]; p = 0.040) and the racquet sports group (6.39; [95% CI] [5.13,7.60]; p ≤ 0.001). Subjects using an elliptical-trainer showed the lowest increase in WORMS (- 1.50 [- 0.21, 3.22]; p = 0.002). CONCLUSION: Progression of knee joint degeneration was consistently higher in subjects engaging in high-impact and racquet sports while subjects using an elliptical-trainer showed the smallest changes in structural degeneration. This work was presented during the 2020 Radiological Society of North America Annual meeting.

Detrimental effects of long sedentary bouts on the biomechanical response of cartilage to sliding.

Purpose/Aim: Epidemiological evidence suggests, contrary to popular mythos, that increased exercise/joint activity does not place articular cartilage at increased risk of disease, but instead promotes joint health. One explanation for this might be activity-induced cartilage rehydration; where joint articulation drives restoration of tissue hydration, thickness, and dependent tribomechanical outcomes (e.g., load support, stiffness, and lubricity) lost to joint loading. However, there have been no studies investigating how patterning of intermittent articulation influences the hydration and biomechanical functions of cartilage.Materials and Methods: Here we leveraged the convergent stationary contact area (cSCA) testing configuration and its unique ability to drive tribological rehydration, to elucidate how intermittency of activity affects the biomechanical functions of bovine stifle cartilage under well-controlled sliding conditions that have been designed to model a typical "day" of human joint activity.Results: For a fixed volume of "daily" activity (30 min) and sedentary time (60 min), breaking up intermittent activity into longer and less-frequent bouts (corresponding to longer continuous sedentary periods) resulted in the exposure of articular cartilage to markedly greater strains, losses of interstitial pressure, and friction coefficients.Conclusions: These results demonstrated that the regularity of ex vivo activity regimens, specifically the duration of sedentary bouts, had a dominant effect on the biomechanical functions of articular cartilage. In more practical terms, the results suggest that brief but regular movement patterns (e.g., every hour) may be biomechanically preferred to long and infrequent movement patterns (e.g., a long walk after a sedentary day) when controlling for daily activity volume (e.g., 30 min).

Management of knee articular cartilage injuries in athletes: chondroprotection, chondrofacilitation, and resurfacing.

UNLABELLED: Articular cartilage defects of the knee are common among athletes where the physical demands of sport result in significant stresses on joints. Chondral defects are associated with pain and functional impairment that limit sporting participation and may progress to joint degeneration and frank arthritis. Management of established chondral lesions aims to allow athletes to return to high-impact sports and can be considered in terms of protection of existing cartilage, chondrofacilitation, and resurfacing. Repaired and regenerated cartilage must closely resemble and function like normal hyaline cartilage, and this ability may be the most significant factor for the return to sport. Based on our experiences and the available literature, we outline how athletes can best protect their cartilage, how physicians can facilitate intrinsic repair of established lesions, and which methods of cartilage restoration or resurfacing should be used in different situations. LEVEL OF EVIDENCE: IV.

Prognostic Factors on Preoperative MRI for Patient-Reported Outcomes After Posterior Medial Meniscus Root Repair.

Background: Repair of posterior medial meniscus root (PMMR) tears has demonstrated favorable outcomes and may prevent rapid progression of knee osteoarthritis; however, there is a paucity of data regarding prognostic factors affecting postoperative outcomes. Purpose/Hypothesis: The purpose of this study was to identify factors on preoperative magnetic resonance imaging (MRI) that predict postoperative outcomes after PMMR repair. It was hypothesized that patients with increasing levels of degenerative changes as evaluated through semiquantitative preoperative MRI scans would have worse postoperative patient-reported outcome (PRO) scores. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent PMMR repair between 2012 and 2020 and had minimum 2-year follow-up data were enrolled. Pre- and postoperative visual analog scale pain scores and postoperative PRO surveys including the Patient-Reported Outcomes Measurement Information System-Physical Function, Lysholm knee score, and Knee injury and Osteoarthritis Outcome Score (KOOS) were collected. Patients who achieved the Patient Acceptable Symptom State (PASS) on the KOOS subscales were reported. Two fellowship-trained musculoskeletal radiologists reviewed preoperative MRIs and calculated the Whole-Organ Magnetic Resonance Imaging Score for meniscus, cartilage, bone marrow edema-like lesions (BMELL), and meniscal extrusion. Statistical analysis was performed using the 2-sample t test, Mann-Whitney test, and Fisher exact test for categorical variables. Results: A total of 29 knees in 29 patients were evaluated (22 female, 7 male; mean age at surgery, 52.3 ± 9.9 years; body mass index, 27.6 ± 5.6 kg/m2; mean follow-up, 59.6 ± 26.5 months). Visual analog scale for pain scores decreased significantly from preoperatively (4.9 ± 2.0) to final follow-up (1.6 ± 1.9) (P < .001), and the percentage of patients meeting the PASS ranged from 44.8% for KOOS Sport and Recreation to 72.4% for KOOS Pain and KOOS Quality of Life. Patients with medial tibial BMELL (MT-BMELL) had significantly lower KOOS Symptoms scores (76.1 ± 17.3 vs 88.4 ± 9.7 without MT-BMELL; P = .032). Cartilage quality and presence of meniscal extrusion were not associated with outcomes. Conclusion: Patients with MT-BMELL on their preoperative MRI in the setting of PMMR tear were found to have worse KOOS Symptoms scores after PMMR repair.

Markers of Pain in 3 Different Murine Models of Posttraumatic Osteoarthritis: A Comparison Using Gait Analysis, Imaging, Histology, and Gene Expression.

BACKGROUND: Animal models play an important role in studying posttraumatic osteoarthritis (PTOA) disease progression. Different models exist, such as destabilization of the medial meniscus (DMM), anterior cruciate ligament (ACL) surgical transection (ACLs), and noninvasive ACL rupture. PURPOSE: To study the effects of PTOA on nociception in 3 different murine models and to relate these findings to macroscopic and microscopic changes in joint tissues. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 42 male C57BL/6 mice, 12 weeks old, were randomly assigned to 4 groups: intact control (n = 10), DMM (n = 10), ACLs (n = 11), and closed ACL rupture (ACLc; n = 11) groups. Gait analysis was performed on 5 mice from the DMM group and 6 mice from ACLs and ACLc groups at 0, 1, 2, 4, 8, and 12 weeks after injury. At the 12-week time point, all mice underwent radiographs and then either micro-computed tomography imaging followed by histology and immunohistochemistry or gene expression analysis of the dorsal root ganglion and tibialis anterior muscle. RESULTS: The peripheral and central pain markers were expressed at significantly higher levels in the synovium of both ACL injury groups when compared with the DMM group. Muscle atrophy genes were significantly upregulated in the ACL injury groups. Pain-related gait behavior started at 4 weeks for the ACL rupture groups and at 12 weeks for the DMM group. High-resolution radiographic imaging and histology demonstrated divergent changes in bone microstructure between the ACLs and DMM groups, suggesting different mechanical loading environments in these models. CONCLUSION: The principal finding of this study is the presence of markers of nociception at both the gene and the protein levels, with earlier expression in the ACL injury groups when compared with the DMM group. The second finding of this study is that the noninvasive ACL rupture model demonstrated changes comparable with those of the commonly used surgical ACL transection model, supporting use of this clinically realistic model in future studies of PTOA. CLINICAL RELEVANCE: Quantitative clinical outcomes (imaging, pain scale, gait changes) related to osteoarthritis severity in an animal study, allowing for better understanding of clinical outcomes of osteoarthritis progression after ACL injuries in humans.

Preoperative diagnosis of knee cartilage, meniscal, and ligament injuries by magnetic resonance imaging.

PURPOSE: The purpose of the study was to report on the current accuracy measures specific to 1.5-Tesla MRI of the knee in the patient population prone to injuries of the anterior cruciate ligament (ACL), the menisci, and the articular cartilage. METHODS: We accrued patients between January 2018 through August 2021 who underwent a preoperative MRI and were diagnosed with an articular cartilage injury either due to unevenness of articular cartilage in T2-weighted sequences or due to the irregularity of subchondral bone in T1-weighted sequences. All patients were treated arthroscopically. Sensitivity, specificity, and accuracy were calculated for the detection of ACL, meniscus, and cartilage injuries. A P-value of < 0.05 represented statistical significance. RESULTS: One-hundred and forty-seven cases which included 150 knee joints were enrolled in this study. The mean age at the time of surgery was 42.9 years-old. The sensitivity in the diagnosis of ACL injuries was significantly greater than that in the diagnosis of cartilage injuries (P = 0.0083). The ratios of the equality of operative indication in 6 recipient sites were found to be between 90.0% and 96.0%. The diagnostic critical point was within a 1 cm in diameter. CONCLUSION: The diagnostic sensitivity in cartilage injuries was significantly lower than ones of ACL and meniscal injuries. The ratios of the equality of operative indication was determined to be between 90.0% and 96.0%, if we consider the unevenness of articular cartilage or the irregularity of subchondral bone. LEVEL OF EVIDENCE: Level III, Prospective diagnostic cohort study.

Meniscal and Articular Cartilage Predictors of Outcome After Revision ACL Reconstruction: A 6-Year Follow-up Cohort Study.

BACKGROUND: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction. PURPOSE: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patient's outcome at 6-year follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Marx Activity Rating Scale. Patients were followed up at 6 years and asked to complete the identical set of outcome instruments. Regression analysis assessed the meniscal and articular cartilage pathology risk factors for clinical outcomes 6 years after revision ACL reconstruction. RESULTS: An overall 1234 patients were enrolled (716 males, 58%; median age, 26 years). Surgeons reported the pathology at the time of revision surgery in the medial meniscus (45%), lateral meniscus (36%), medial femoral condyle (43%), lateral femoral condyle (29%), medial tibial plateau (11%), lateral tibial plateau (17%), patella (30%), and trochlea (21%). Six-year follow-up was obtained on 79% of the sample (980/1234). Meniscal pathology and articular cartilage pathology (medial femoral condyle, lateral femoral condyle, lateral tibial plateau, trochlea, and patella) were significant drivers of poorer patient-reported outcomes at 6 years (IKDC, KOOS, WOMAC, and Marx). The most consistent factors driving outcomes were having a medial meniscal excision (either before or at the time of revision surgery) and patellofemoral articular cartilage pathology. Six-year Marx activity levels were negatively affected by having either a repair/excision of the medial meniscus (odds ratio range, 1.45-1.72; P≤ .04) or grade 3-4 patellar chondrosis (odds ratio, 1.72; P = .04). Meniscal pathology occurring before the index revision surgery negatively affected scores on all KOOS subscales except for sports/recreation (P < .05). Articular cartilage pathology significantly impaired all KOOS subscale scores (P < .05). Lower baseline outcome scores, higher body mass index, being a smoker, and incurring subsequent surgery all significantly increased the odds of reporting poorer clinical outcomes at 6 years. CONCLUSION: Meniscal and chondral pathology at the time of revision ACL reconstruction has continued significant detrimental effects on patient-reported outcomes at 6 years after revision surgery.

Computational assessment on the impact of collagen fiber orientation in cartilages on healthy and arthritic knee kinetics/kinematics.

BACKGROUND: The inhomogeneous distribution of collagen fiber in cartilage can substantially influence the knee kinematics. This becomes vital for understanding the mechanical response of soft tissues, and cartilage deterioration including osteoarthritis (OA). Though the conventional computational models consider geometrical heterogeneity along with fiber reinforcements in the cartilage model as material heterogeneity, the influence of fiber orientation on knee kinetics and kinematics is not fully explored. This work examines how the collagen fiber orientation in the cartilage affects the healthy (intact knee) and arthritic knee response over multiple gait activities like running and walking. METHODS: A 3D finite element knee joint model is used to compute the articular cartilage response during the gait cycle. A fiber-reinforced porous hyper elastic (FRPHE) material is used to model the soft tissue. A split-line pattern is used to implement the fiber orientation in femoral and tibial cartilage. Four distinct intact cartilage models and three OA models are simulated to assess the impact of the orientation of collagen fibers in a depth wise direction. The cartilage models with fibers oriented in parallel, perpendicular, and inclined to the articular surface are investigated for multiple knee kinematics and kinetics. FINDINGS: The comparison of models with fiber orientation parallel to articulating surface for walking and running gait has the highest elastic stress and fluid pressure compared with inclined and perpendicular fiber-oriented models. Also, the maximum contact pressure is observed to be higher in the case of intact models during the walking cycle than for OA models. In contrast, the maximum contact pressure is higher during running in OA models than in intact models. Additionally, parallel-oriented models produce higher maximum stresses and fluid pressure for walking and running gait than proximal-distal-oriented models. Interestingly, during the walking cycle, the maximum contact pressure with intact models is approximately three times higher than on OA models. In contrast, the OA models exhibit higher contact pressure during the running cycle. INTERPRETATION: Overall, the study indicates that collagen orientation is crucial for tissue responsiveness. This investigation provides insights into the development of tailored implants.

Marrow Stimulation Has Relatively Inferior Patient-Reported Outcomes in Cartilage Restoration Surgery of the Knee: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Multiple cartilage repair techniques are available for chondral defects in the knee. Optimal treatment is controversial. PURPOSE: To evaluate change from baseline in the 5 Knee injury and Osteoarthritis Outcome Score (KOOS) subscales among different cartilage repair techniques of the knee. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 1A. METHODS: Medline and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for randomized controlled trials with minimum 1 year follow-up reporting change from baseline KOOS (delta KOOS) subscale values. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. A meta-analysis was performed on the following surgery types: microfracture (Mfx); augmented microfracture techniques (Mfx+Augment); and culture-based therapies, including autologous chondrocyte implantation (ACI) and matrix-assisted autologous chondrocyte implantation (MACI). A random-effects metaregression model was used. RESULTS: A total of 14 randomized trials with a total of 775 patients were included. The KOOS Sport and Recreation (Sport) and KOOS Quality of Life (QOL) were the 2 most responsive subscales after operative intervention. Outcomes from Mfx and Mfx+Augment were not different in any of the 5 KOOS subscales (minimum P > .3). The mean delta KOOS Sport after ACI/MACI was 9.9 points greater than after Mfx (P = .021) and 11.7 points greater than after Mfx+Augment (P = .027). Longer follow-up time correlated with greater delta KOOS Sport (P = .028). Larger body mass index led to greater delta KOOS QOL (P = .045). Larger cartilage defect size correlated with greater delta KOOS Pain and KOOS Activities of Daily Living scores (P = .023 and P = .002, respectively). CONCLUSION: The KOOS Sport and QOL were the most responsive subscales after cartilage restoration surgery of the knee. Culture-based therapies (ACI/MACI) led to clinically relevant improvements in the KOOS Sport score compared with marrow stimulation and may be a more appropriate treatment in younger and more active individuals. There were no benefits to Mfx+Augment over Mfx alone in any of the KOOS subscales.

A self-compensated spin-locking scheme for quantitative R1ρ dispersion MR imaging in ordered tissues.

PURPOSE: To propose a self-compensated spin-locking (SL) method for quantitative R1ρ dispersion imaging in ordered tissues. METHODS: Two pairs of antiphase rotary-echo SL pulses were proposed in a new scheme with each pairs sandwiching one refocusing RF pulse. This proposed SL method was evaluated by Bloch simulations and experimental studies relative to three prior schemes. Quantitative R1ρR dispersion imaging studies with constant SL duration (TSL = 40 ms) were carried out on an agarose (1-4% w/v) phantom and one in vivo human knee at 3 T, using six SL RF strengths ranging from 50 to 1000 Hz. The performances of these SL schemes were characterized with an average coefficient of variation (CV) of the signal intensities in agarose gels and the sum of squared errors (SSE) for quantifying in vivo R1ρ dispersion of the femoral and tibial cartilage. RESULTS: The simulations demonstrate that the proposed SL scheme was less prone to B0 and B1 field inhomogeneities. This theoretical prediction was supported by fewer image banding artifacts and less signal fluctuation signified by a reduced CV (%) on the phantom without R1ρ dispersion (i.e., 4.04 ± 1.36 vs. 18.87 ± 4.46 or 6.66 ± 2.92 or 5.71 ± 2.05 for others), and further by mostly decreased SSE (*10-3) for characterizing R1ρ dispersion of the femoral (i.e., 0.3 vs. 1.2 or 0.4 or 0.1) and tibial (i.e., 0.4 vs. 7.2 or 3.2 or 2.8) cartilage. CONCLUSION: The proposed SL scheme is less sensitive to B0 and B1 field artifacts for a wide range of SL RF strengths and thus more suitable for quantitative R1ρ dispersion imaging in ordered tissues.

Low Rates of Radiographic Knee Osteoarthritis 5 Years After ACL Reconstruction or Rehabilitation Alone: The Delaware-Oslo ACL Cohort Study.

BACKGROUND: Patients and clinicians often struggle to choose the optimal management strategy for posttraumatic knee osteoarthritis (OA) after an anterior cruciate ligament (ACL) injury. An evaluation of radiographic outcomes after a decision-making and treatment algorithm applicable in clinical practice can help to inform future recommendations and treatment choices. PURPOSE: To describe and compare 5-year radiographic outcomes and knee pain in individuals who had gone through our decision-making and treatment algorithm and chosen (1) early (<6 months) ACL reconstruction (ACLR) with pre- and postoperative rehabilitation, (2) delayed (>6 months) ACLR with pre- and postoperative rehabilitation, or (3) progressive rehabilitation alone. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: We included 276 patients with unilateral ACL injury from a prospective cohort study. Patients chose management using a shared decision-making process and treatment algorithm, and 5-year postoperative radiographs of the index and contralateral knees were assessed using the Kellgren and Lawrence (K&L) classification and minimum joint space width measurements. We defined radiographic tibiofemoral OA as K&L grade ≥2 and knee pain as a Knee injury and Osteoarthritis Outcome Score for Pain ≤72. To further explore early radiographic changes, we included alternative cutoffs for radiographic knee OA using K&L grade ≥2/osteophyte (definite osteophyte without joint space narrowing) and K&L grade ≥1. RESULTS: At 5 years, 64% had undergone early ACLR; 11%, delayed ACLR; and 25%, progressive rehabilitation alone. Radiographic examination was attended by 187 patients (68%). Six percent of the cohort had radiographic tibiofemoral OA (K&L grade ≥2) in the index knee; 4%, in the contralateral knee. Using the alternative cutoffs at K&L grade ≥2/osteophyte and K&L grade ≥1, the corresponding numbers were 20% and 33% in the index knee and 18% and 29% in the contralateral knee. Six percent had a painful index knee. There were no statistically significant differences in any radiographic outcomes or knee pain among the 3 management groups. CONCLUSION: There were no statistically significant differences in any 5-year radiographic outcomes or knee pain among the 3 management groups. Very few of the patients who participated in our decision-making and treatment algorithm had knee OA or knee pain at 5 years.

Multiparametric MRI characterization of knee articular cartilage and subchondral bone shape in collegiate basketball players.

Magnetic resonance imaging (MRI) is commonly used to evaluate the morphology of the knee in athletes with high-knee impact; however, complex repeated loading of the joint can lead to biochemical and structural degeneration that occurs before visible morphological changes. In this study, we utilized multiparametric quantitative MRI to compare morphology and composition of articular cartilage and subchondral bone shape between young athletes with high-knee impact (basketball players; n = 40) and non-knee impact (swimmers; n = 25). We implemented voxel-based relaxometry to register all cases to a single reference space and performed a localized compositional analysis of T 1ρ - and T 2 -relaxation times on a voxel-by-voxel basis. Additionally, statistical shape modeling was employed to extract differences in subchondral bone shape between the two groups. Evaluation of cartilage composition demonstrated a significant prolongation of relaxation times in the medial femoral and tibial compartments and in the posterolateral femur of basketball players in comparison to relaxation times in the same cartilage compartments of swimmers. The compositional analysis also showed depth-dependent differences with prolongation of the superficial layer in basketball players. For subchondral bone shape, three total modes were found to be significantly different between groups and related to the relative sizes of the tibial plateaus, intercondylar eminences, and the curvature and concavity of the patellar lateral facet. In summary, this study identified several characteristics associated with a high-knee impact which may expand our understanding of local degenerative patterns in this population.

Forces at the Anterior Meniscus Attachments Strongly Increase Under Dynamic Knee Joint Loading.

BACKGROUND: The anatomic appearance and biomechanical and clinical importance of the anterior meniscus roots are well described. However, little is known about the loads that act on these attachment structures under physiological joint loads and movements. HYPOTHESES: As compared with uniaxial loading conditions under static knee flexion angles or at very low flexion-extension speeds, more realistic continuous movement simulations in combination with physiological muscle force simulations lead to significantly higher anterior meniscus attachment forces. This increase is even more pronounced in combination with a longitudinal meniscal tear or after total medial meniscectomy. STUDY DESIGN: Controlled laboratory study. METHODS: A validated Oxford Rig-like knee simulator was used to perform a slow squat, a fast squat, and jump landing maneuvers on 9 cadaveric human knee joints, with and without muscle force simulation. The strains in the anterior medial and lateral meniscal periphery and the respective attachments were determined in 3 states: intact meniscus, medial longitudinal tear, and total medial meniscectomy. To determine the attachment forces, a subsequent in situ tensile test was performed. RESULTS: Muscle force simulation resulted in a significant strain increase at the anterior meniscus attachments of up to 308% (P < .038) and the anterior meniscal periphery of up to 276%. This corresponded to significantly increased forces (P < .038) acting in the anteromedial attachment with a maximum force of 140 N, as determined during the jump landing simulation. Meniscus attachment strains and forces were significantly influenced (P = .008) by the longitudinal tear and meniscectomy during the drop jump simulation. CONCLUSION: Medial and lateral anterior meniscus attachment strains and forces were significantly increased with physiological muscle force simulation, corroborating our hypothesis. Therefore, in vitro tests applying uniaxial loads combined with static knee flexion angles or very low flexion-extension speeds appear to underestimate meniscus attachment forces. CLINICAL RELEVANCE: The data of the present study might help to optimize the anchoring of meniscal allografts and artificial meniscal substitutes to the tibial plateau. Furthermore, this is the first in vitro study to indicate reasonable minimum stability requirements regarding the reattachment of torn anterior meniscus roots.

Contralateral Lateral Femoral Condyle Allografts Provide an Acceptable Surface Match for Simulated Classic Osteochondritis Dissecans Lesions of the Medial Femoral Condyle.

BACKGROUND: Osteochondral allograft transplantation is an effective technique for repairing large lesions of the medial femoral condyle (MFC), but its use is limited by graft availability. PURPOSE/HYPOTHESIS: The present study aimed to determine whether contralateral lateral femoral condyle (LFC) allografts can provide an acceptable surface match for posterolateral MFC lesions characteristic of classic osteochondritis dissecans (OCD). The hypothesis was that LFC and MFC allografts will provide similar surface contour matches in all 4 quadrants of the graft for posterolateral MFC lesions characteristic of OCD. STUDY DESIGN: Controlled laboratory study. METHODS: Ten fresh-frozen recipient human MFCs were each size-matched to 1 ipsilateral medial and 1 contralateral LFC donor (N = 30 condyles). After a nano-computed tomography (nano-CT) scan of the native recipient condyle, a 20-mm circular osteochondral "defect" was created 1 cm posterior and 1 cm medial to the roof of the intercondylar notch (n = 10). A size-matched, random-order donor MFC or LFC plug was then harvested, transplanted, and scanned with nano-CT. Nano-CT scans were then reconstructed, registered to the initial scan of the recipient MFC, and processed in MATLAB to determine the height deviation (d RMS) between the native and donor surfaces and percentage area unacceptably (>1 mm) proud (%A proud) and sunken (%A sunk). Circumferential step-off height (h RMS) and percentage circumference unacceptably (>1 mm) proud (%C proud) and sunken (%C sunk) were measured using DragonFly software. The process was then repeated for the other allograft plug. RESULTS: Both MFC and LFC plugs showed acceptable step-off heights in all 4 quadrants (range, 0.53-0.94 mm). Neither allograft type nor location within the defect had a significant effect on step-off height (h RMS), surface deviation (d RMS), %A proud, or %A sunk. In general, plugs were more unacceptably sunken than proud (MFC, 13.4% vs 2.4%; LFC, 13.2% vs 8.1%), although no significant differences in %C sunk were seen between allograft types or locations within the defect. In LFC plugs, %C proud in the lateral quadrant (28.0% ± 26.1%) was significantly greater compared with all other quadrants (P = .0002). CONCLUSION: The present study demonstrates that 20-mm contralateral LFC allografts provide an acceptable surface match for posterolateral MFC lesions characteristic of OCD. CLINICAL RELEVANCE: With comparable surface matching, MFC and LFC allografts can be expected to present similar stresses on the knee joint and achieve predictably positive clinical outcomes, thus improving donor availability and reducing surgical wait times for matches.

A Translational Porcine Model for Human Cell-Based Therapies in the Treatment of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Injury.

BACKGROUND: There is a high incidence of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) injury, and these injuries represent an enormous health care economic burden. In an effort to address this unmet clinical need, there has been increasing interest in cell-based therapies. PURPOSE: To establish a translational large animal model of PTOA and demonstrate the feasibility of intra-articular human cell-based interventions. STUDY DESIGN: Descriptive laboratory study. METHODS: Nine Yucatan mini-pigs underwent unilateral ACL transection and were monitored for up to 12 weeks after injury. Interleukin 1 beta (IL-1ß) levels and collagen breakdown were evaluated longitudinally using enzyme-linked immunosorbent assays of synovial fluid, serum, and urine. Animals were euthanized at 4 weeks (n = 3) or 12 weeks (n = 3) after injury, and injured and uninjured limbs underwent magnetic resonance imaging (MRI) and histologic analysis. At 2 days after ACL injury, an additional 3 animals received an intra-articular injection of 107 human bone marrow-derived mesenchymal stem cells (hBM-MSCs) combined with a fibrin carrier. These cells were labeled with the luciferase reporter gene (hBM-MSCs-Luc) as well as fluorescent markers and intracellular iron nanoparticles. These animals were euthanized on day 0 (n = 1) or day 14 (n = 2) after injection. hBM-MSC-Luc viability and localization were assessed using ex vivo bioluminescence imaging, fluorescence imaging, and MRI. RESULTS: PTOA was detected as early as 4 weeks after injury. At 12 weeks after injury, osteoarthritis could be detected grossly as well as on histologic analysis. Synovial fluid analysis showed elevation of IL-1ß shortly after ACL injury, with subsequent resolution by 2 weeks after injury. Collagen type II protein fragments were elevated in the synovial fluid and serum after injury. hBM-MSCs-Luc were detected immediately after injection and at 2 weeks after injection using fluorescence imaging, MRI, and bioluminescence imaging. CONCLUSION: This study demonstrates the feasibility of reproducing the chondral changes, intra-articular cytokine alterations, and body fluid biomarker findings consistent with PTOA after ACL injury in a large animal model. Furthermore, we have demonstrated the ability of hBM-MSCs to survive and express transgene within the knee joint of porcine hosts without immunosuppression for at least 2 weeks. CLINICAL RELEVANCE: This model holds great potential to significantly contribute to investigations focused on the development of cell-based therapies for human ACL injury-associated PTOA in the future (see Appendix Figure A1, available online).

Outcomes After Fresh Osteochondral Allograft Transplantation for Medium to Large Chondral Defects of the Knee.

BACKGROUND: Articular cartilage defects of the knee can significantly impair function among young, high-demand patients. There are several techniques for chondral restoration, including osteochondral allograft transplantation (OCA), that may alleviate pain and re-create the native anatomy. However, clinical outcomes among athletic cohorts are limited. PURPOSE: To evaluate the efficacy and functional outcomes of OCA for medium to large osteochondral defects of the knee in physically active United States military servicemembers. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A military health care database was queried to identify all OCA procedures performed between January 2009 and March 2013. Inclusion criteria were army personnel with a minimum of 2 years' follow-up. Exclusion criteria included incomplete follow-up, inaccurate coding, and nonmilitary status. Variables of interest included sex, age, lesion location, grade and size of the lesion, body mass index, tobacco use, preoperative and postoperative visual analog scale (VAS) scores for pain, and presence of perioperative complications. Overall failure was defined as the inability to return to preoperative functional activities because of persistent knee complaints (clinical failure) or a revision cartilage procedure or arthroplasty (surgical failure). RESULTS: A total of 61 patients (52 male; mean age, 31.7 years) were identified, with a mean 46.2-month follow-up. The mean VAS pain score improved from 4.10 ± 2.17 preoperatively to 2.68 ± 2.73 postoperatively (P < .0009), and only 6 (9.8%) required a subsequent revision chondral procedure. Overall, 39 patients (63.9%) were able to return to a level of activity that allowed for the completion of military duties. Risk factors for clinical failure were preoperative body mass index, preoperative pain as measured on the VAS, and moderate to severe postoperative pain on the VAS. The risk factor for surgical failure was the presence of a complication. Risk factors for overall failure were the presence of a complication and moderate to severe postoperative pain on the VAS. CONCLUSION: OCA provided moderate success in retaining active-duty army servicemembers. Approximately two-thirds of patients undergoing OCA were able to return to their preinjury occupational activity, while approximately 57% of patients returned to prior levels without a subsequent revision chondral procedure or arthroplasty.

Prevalence of Asymptomatic Intra-articular Changes of the Knee in Adult Professional Soccer Players.

BACKGROUND: Currently, there are few data on the association between participation in soccer and the condition of the knee joints in adult professional players. HYPOTHESIS: A high percentage of professional soccer players will have asymptomatic intra-articular changes of the knee. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: The condition of the intra-articular structures (osteophytes, cartilage, and menisci) in 94 knee joints of 47 adult professional soccer players (mean ± SD age, 25.7 ± 4.6 years; body mass index, 22.8 ± 1.4 kg/m2) was analyzed. A 1.5-T magnetic resonance imaging scanner was used to perform the imaging, and the anonymized data were analyzed by 2 experienced radiologists. RESULTS: Cartilage of both knee joints was affected in 97.9% of soccer players. Meniscal lesions were detected in 97.8% of joints, affecting both joints in 93.6% of athletes. Grade 2 cartilage lesions were the most prevalent (36%-60% depending on the lesion site), and grade 4 lesions were detected in 12.7% of joints. The medial femoral condyle and medial tibial plateau were most frequently affected by cartilage lesions (85.1%). Among meniscal lesions, grade 2 lesions were the most prevalent, being detected in 71% of the cases. Grade 3 lesions were detected in 13.8% of the joints. The posterior horn of the lateral meniscus was the most common site of meniscal lesions (affected in 95.7% of the joints). Osteophytes were detected in 4.2% of joints. CONCLUSION: The prevalence of asymptomatic cartilage and meniscal lesions in the knees of adult professional soccer players is extremely high and is not associated with the reduction of sports involvement. This research should promote the correct interpretation of magnetic resonance imaging data obtained from soccer players with acute trauma and the reduction of the number of unwarranted surgical procedures.

Chondrocytes From Device-Minced Articular Cartilage Show Potent Outgrowth Into Fibrin and Collagen Hydrogels.

BACKGROUND: Transplantation of autologous minced cartilage is an established procedure to repair chondral lesions. It relies on the migration of chondrocytes out of cartilage particles into a biomaterial. So far, there is no efficient way to finely mince cartilage. No consensus exists on the nature of the biomaterial to be used to promote chondrocyte migration. PURPOSE/HYPOTHESIS: This study aimed to investigate the potential clinical use of a custom-made mincing device as well as a possible alternative biomaterial to fibrin glue. The device was tested for its effect on chondrocyte viability and on subsequent chondrocyte migration into either a fibrin or a collagen gel. We hypothesized that device mincing would allow finer cutting and consequently more cell migration and that the gelation mechanism of the collagen biomaterial, which uses the clotting of platelet-rich plasma, would enhance matrix production by outgrown chondrocytes. STUDY DESIGN: Controlled laboratory study. METHODS: Cartilage from 12 patients undergoing knee arthroplasty was taken from the femoral condyles and subsequently either hand minced or device minced. The viability and the degree of outgrowth were quantified with live/dead assay on the generated cartilage particles and on the gels in which these particles were embedded, respectively. Matrix deposition in the biomaterials by the outgrown cells was investigated with histology. RESULTS: The device allowed rapid mincing of the cartilage and produced significantly smaller pieces than hand mincing. The initial chondrocyte viability in cartilage particles dropped by 25% with device mincing as compared with no mincing. However, the viability in hand-minced, device-minced, and unminced samples was no longer different after 7 and 28 days in culture. Outgrowth scores were similar among the 3 groups. Fibrin and collagen biomaterials equally supported chondrocyte outgrowth and survival, but neither promoted matrix deposition after in vitro culture. CONCLUSION: The outgrowth potential, the viability after 28 days in culture, and the matrix deposition were not different between the mincing techniques and the tested biomaterials, yet device mincing is faster and results in significantly smaller cartilage particles. CLINICAL RELEVANCE: Device mincing could become the standard method to mince cartilage for second-generation cartilage repair techniques.

Equivalent 10-Year Outcomes After Implantation of Autologous Bone Marrow-Derived Mesenchymal Stem Cells Versus Autologous Chondrocyte Implantation for Chondral Defects of the Knee.

BACKGROUND: The use of bone marrow-derived mesenchymal stem cells (BMSCs) in cartilage repair procedures circumvents some of the limitations of autologous chondrocyte implantation (ACI), but long-term outcomes for this newer procedure are lacking. The authors previously reported comparable outcomes for the 2 procedures at 2-year follow-up. PURPOSE/HYPOTHESIS: The purpose was to compare the long-term clinical outcomes of ACI versus BMSCs. It was hypothesized that there would be no significant difference between the groups in terms of patient-reported outcome scores and safety outcomes at 10-year follow-up. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Seventy-two patients who underwent either ACI or BMSC implantation-matched in terms of age and lesion site- were followed up to a median of at least 10 years. Patients were assessed with the 36-item Short Form Health Survey (SF-36), the International Knee Documentation Committee knee evaluation form, the Lysholm Knee Score, and the Tegner Activity Scale. In addition, information was obtained regarding any additional surgical procedures as well as safety data, with particular attention to infection and tumor formation. RESULTS: There was an improvement in all patient-reported outcomes scores apart from the Mental Component Summary of the SF-36 after cartilage repair surgery. There was no significant difference in any of the patient-reported outcomes between cohorts at any time point. Six and 5 patients in the ACI and BMSC groups, respectively, underwent subsequent surgical procedures, including 1 total knee replacement in the BMSC group. None of the patients in either group developed any deep infection or tumor within the follow-up period. CONCLUSION: BMSC implantation used for the treatment of chondral defects of the knee appears to result in equivalent clinical outcomes to first-generation ACI at up to 10 years, with no apparent increased tumor formation risk.