Effects of different surgical procedures for meniscus injury on two-year clinical and radiological outcomes after anterior cruciate ligament reconstructions. -TMDU MAKS study.

BACKGROUND: The treatment of meniscus injuries combined with anterior cruciate ligament (ACL) reconstruction would be important to improve outcomes after ACL reconstruction. However, the effects of treatment methods for meniscus after ACL reconstruction have not been thoroughly investigated. The objective of this study was to investigate the effects of treatment methods for meniscus on clinical and radiological outcomes at 2 years after ACL reconstruction. METHODS: Three-hundred and eighteen patients with primary ACL reconstruction using autologous hamstring tendon registered in our multicenter study database and who were followed up for 2 years were included. They were then divided into 3 groups, the no meniscal lesion/untreated group (n = 149), the meniscal repair group (n = 139), and the meniscal resection group (n = 30). Patient-based subjective evaluations (Lysholm score, Knee injury and Osteoarthritis Outcome score and International Knee Documentation Committee subjective score), objective evaluations (Lachman test, pivot shift test and KT measurement), and radiological measurements (medial and lateral joint space width) were compared among the 3 groups preoperatively and at 2 years follow-up. RESULTS: All subjective scores and objective evaluations significantly improved in all groups without significant differences among the groups postoperatively. Regarding radiological findings, the medial joint space width significantly decreased only in the resection group during the 2-year period, and the medial joint space width in the resection group was significantly smaller than that of the other groups at the 2-year follow-up. Moreover, the medial joint space width significantly decreased during the 2-year period when MM was resected. CONCLUSIONS: In radiological findings, medial meniscus resection decreased medial joint space width two years after ACL reconstruction. On the other hand, treatment methods for meniscus neither significantly affected subjective nor objective findings until the 2-year follow-up. LEVEL OF EVIDENCE: Ⅱ, Cohort study.

Second-look arthroscopy after meniscus repair and synovial mesenchymal stem cell transplantation to treat degenerative flaps and radial tears of the medial meniscus: A case report.

BACKGROUND: The purpose of this study was to compare arthroscopic findings of a degenerative flap and radial tear of the medial meniscus (MM) before and one year after treatment by meniscus repair and synovial mesenchymal stem cell (MSC) transplantation. METHODS: Patients with a degenerative flap and radial MM tear that would generally be treated by meniscectomy were included. The patients ranged in age from 45 to 62 years and all underwent meniscus repair and synovium harvest at time 0. The digested synovium was cultured with autologous serum for 12 days, and an average of 4 × 107 MSCs were transplanted at two weeks. A second-look arthroscopy was performed at 52 weeks (n = 6). The average duration of symptoms was 24 months. For flap tears, arthroscopic findings were quantified in terms of the presence, stability, and smoothness of the meniscus at each zone and area. The Lysholm score was evaluated throughout the 52 week follow-up. RESULTS: Four patients with MM flap tears showed deficiencies in the central area at the posterior junctional zone before treatment, but this zone was completely restored to a stable and smooth condition in two patients and partially restored in the other two patients. The arthroscopy score for a flap tear at the central area of the posterior junctional zone was 0.3 ± 0.5 before treatment and 4.3 ± 2.1 after treatment. The score was significantly higher after treatment (p < 0.05, n = 4). The original radial MM tears in two patients were healed one year after treatment. Lysholm scores were significantly higher at 4 and 52 weeks after treatment than before treatment (n = 6). CONCLUSIONS: Arthroscopic findings for a degenerative flap and radial tear of the MM were improved at the central area of the posterior junctional zone one year after meniscus repair and MSC transplantation.

Consideration for the validation of clinical laboratory methods in nonclinical fields.

In new drug development, cells or animals are treated with the selected candidate compound to confirm its efficacy and safety in nonclinical studies. Clinical laboratory tests are carried out using samples from experimental animals in these studies. The clinical laboratory test method validation in nonclinical fields should be conducted keeping in mind that the circumstances differ from those in clinical settings. However, the validation procedures have not been systematically integrated into any standard. The considerations in this paper set out systematically practical guidance for the validation of quantitative analytical methods for fluid samples collected from animal studies, for the purpose of ensuring that laboratory test method validation is conducted in nonclinical fields at an enough level.

Knee laxity, lateral meniscus tear and distal femur morphology influence pivot shift test grade in ACL injury patients.

PURPOSE: Although several factors have been considered to be associated with pivot shift test grade in ACL injured patients, a conclusion regarding which factors contribute to the pivot shift test grade has not been reached. The purpose of this study was to identify factors associated with preoperative pivot shift test grade. METHODS: Three hundred and sixty-six consecutive patients who underwent ACL reconstruction in our hospital were enrolled in the study. Patients were divided into two groups on the basis of preoperative pivot shift test grade (Mild: grade 0-3, Severe: grade 4-6). First, 13 independent variables (age, gender, period from injury to surgery, hyperextension, KT measurement, contralateral side pivot shift test grade, medial and lateral tibial slope, lateral condyle length, lateral condyle height, distal femoral condyle offset, medial and lateral meniscus tear) were analyzed by one-way ANOVA and Chi-squared test. Binary Logistic regression was then performed based on the results of univariate analyses (independent variables of p < 0.2 were included). RESULTS: Hyperextension, lateral meniscus tear, contralateral side pivot shift test grade, distal femoral condyle offset and KT measurement were identified as risk factors for preoperative pivot shift grade via logistic regression analysis. CONCLUSION: The current study revealed that hyperextension, lateral meniscus tear, contralateral side pivot shift test grade, distal femoral condyle offset and anterior instability were associated with preoperative pivot shift grade. Patients with above factors that cannot be modified during surgery may need special consideration when ACL reconstruction is performed, as greater preoperative pivot shift has been proven to be a risk factor for residual pivot shift after ACL reconstruction. LEVEL OF EVIDENCE: III.

Two- and three-dimensional optical coherence tomography to differentiate degenerative changes in a rat meniscectomy model.

Optical coherence tomography (OCT) is an attractive tool for evaluating cartilage. We developed an OCT system that reconstructs and analyzes a three-dimensional (3D) OCT image by determining the cartilage surface and cartilage-bone boundary from the image taken with currently available OCT devices. We examined the usefulness of 3D renderings of OCT images. In a rat meniscectomized model, the tibia was harvested after 0, 2, 4, or 8 weeks (n = 6). We scanned 300 slices in the y-plane to cover a 4 × 3 × 6-mm section (x-plane; 10 µm × 400 pixels, y-plane; 10 µm × 300 pixels, z-plane; 12.66 µm × 500 pixels) of the medial tibial cartilage. The cartilage surface line and the cartilage-bone boundary were plotted semi-automatically. Slices from 300 two-dimensional (2D) sequential images were systematically and visually checked and corrected, as necessary. We set a region of interest in the cartilage and quantified the cartilage volume in the 3D image. The Osteoarthritis Research Society International (OARSI) histological score was also obtained. The cartilage volume determined using 3D OCT images was 0.291 ± 0.022 mm3 in the normal, 0.264 ± 0.009 mm3 at 2 weeks, 0.210 ± 0.012 mm3 at 4 weeks, and 0.205 ± 0.011 mm3 at 8 weeks. The cartilage volume significantly decreased at 4 and 8 weeks and was significantly correlated with the OARSI histological score (r = -0.674; P = .002). Although the 3D image information could be obtained from the 2D images, the 3D OCT images provided easier-to-understand information because the 3D reconstructed cartilage provided information about the smoothness of the surface, the area, and depth of the defect at a glance.

Morphological changes in synovial mesenchymal stem cells during their adhesion to the meniscus.

Synovial mesenchymal stem cells (MSCs) are an attractive cell source for transplantation because of their high chondrogenic potential, especially in areas like the meniscus of the knee. A synovial MSC suspension placed onto the meniscus for 10 min promoted healing of repaired meniscal tears that generally do not heal. Here, we quantified the proportion of human synovial MSCs that adhered to a porcine abraded meniscus, clarified their morphological changes, and revealed the mechanism by which the synovial MSCs adhered to the meniscus. The numbers of adhering cells at immediately after 10, 60 min and 6, 24 h after suspension placement were calculated. The meniscus surface was examined by scanning electron microscopy, and 50 cells were randomly selected at each time period, classified, and quantified for each of the six donors. Approximately 28% of the synovial MSCs immediately adhered to the meniscus after placement and the proportion of adhered cells increased further with time. All cells maintained a round shape for 60 min, and then transformed to a mixture of round and semi-flattened cells. By 24 h, flattened cells covered the meniscus. Microspikes were observed in 36% of the floating synovial MSCs and in 76% of the cells on the meniscus shortly after placement on the meniscus, then the proportion of cells with pseudopodia increased. The bleb-dominant cell proportion significantly decreased, and the smooth-dominant cell proportion increased within 60 min. Microspikes or the bodies of synovial MSCs were trapped by meniscal fibers immediately after placement. The proportion of adhered cells increased with time, and the cell morphology changed dynamically for 24 h as the synovial MSCs adhered to the meniscus. The MSCs in the round morphological state had a heterogeneous morphology. The microspikes, and the subsequent development of pseudopodia, may play an important role in adhesion onto the meniscus.

Investigation of association between the preoperative intra-articular anesthetic test and persistent pain after total knee arthroplasty.

BACKGROUND: A better understanding of the etiology of persistent pain after total knee arthroplasty (TKA) is required to prevent unfavorable outcomes. The purpose of this study was to investigate the association of persistent pain after TKA, patient characteristics, and the remaining pain ratio per the preoperative intra-articular anesthetic test. METHODS: This study included 89 patients who underwent TKA and underwent an intra-articular anesthetic test preoperatively. The remaining pain ratio out of 100 percent 30 min after intra-articular anesthetic injection and demographic data were also evaluated preoperatively. Numerical rating scale (NRS) scores for pain during movement (Q1), at rest (Q2), at first movement in the morning (Q3), and during climbing up and down stairs (Q4) were evaluated 1 year after TKA. Multiple linear regression analysis was performed to assess the impact of independent variables on the NRS score for questionnaire No.4. and the remaining pain ratio per the intra-articular anesthetic. RESULTS: The mean remaining pain ratio per the preoperative intra-articular anesthetic test was 29.3%. The NRS score for Q4 was significantly higher than those for any of the other NRS questionnaires administered 1 year after TKA (Q1-Q4, Q2-Q4, P < 0.001; Q3-Q4, P < 0.05). The analysis found the weak correlation between the pain ratio of anesthetic test and the NRS score for Q4 after TKA (R = 0.28, P = 0.018). BMI and preoperative FTA were the major predictors of remaining pain ratio per the intra-articular anesthetic test (R = 0.40, P = 0.002). CONCLUSION: This study revealed that the remaining pain ratio per the preoperative intra-articular anesthetic test was weakly correlated with persistent pain during climbing up and down stairs 1 year after TKA. In addition, BMI and preoperative FTA were associated with the remaining pain ratio per the preoperative intra-articular anesthetic test.

Correction to: Coronal and sagittal laxity affects clinical outcomes in posterior-stabilized total knee arthroplasty: assessment of well-functioning knees.

Unfortunately, the co-author "Hiroki Katagiri' was omitted in the original publication from the author group. The author name is added here. The original article has been corrected.

Coronal and sagittal laxity affects clinical outcomes in posterior-stabilized total knee arthroplasty: assessment of well-functioning knees.

PURPOSE: Both coronal and sagittal laxity of well-functioning knees after total knee arthroplasty (TKA) was examined, and the correlations between the joint laxity and the clinical outcomes were analyzed to clarify the adequate joint laxity for the prosthesis, and the relationship between the laxity and the outcomes. METHODS: Forty well-functioning TKA knees with a high-flexion posterior-stabilized (PS) prosthesis were studied. All patients were diagnosed as having osteoarthritis with varus deformity and were followed up for 2 years or more. The coronal and sagittal laxity was assessed at extension and flexion, and the correlations between the joint laxity and the clinical outcomes were evaluated. RESULTS: The varus and valgus laxity averaged 5.6 ± 1.8° and 3.6 ± 1.2° at 10° knee flexion, and 7.4 ± 5.1° and 3.6 ± 2.7° at 80° knee flexion, respectively, and the AP laxity at 30° and 75° knee flexion averaged 8.7 ± 3.6 mm and 6.6 ± 2.3 mm, respectively. Knee flexion angle correlated with the joint laxity, while the other outcomes including patient-reported pain and instability were adversely affected by the greater laxity. CONCLUSIONS: This study exhibited the importance of consistent medial laxity both at extension and flexion, which averaged 3.6°. Care should be taken to maintain the medial stability and to obtain adequate laxity both at extension and flexion during surgery. A few degrees of medial tightness can be allowed to achieve excellent clinical results after TKA for preoperative varus knees. LEVEL OF EVIDENCE: Therapeutic study, Level III.

Anatomic femoral tunnel placement is difficult by the transtibial technique: comparison of three different femoral tunnel drilling techniques in double-bundle anterior cruciate ligament reconstructions.

PURPOSE: To compare the position and direction of femoral and tibial tunnels for both the anteromedial bundle (AMB) and posterolateral bundle (PLB) among three different femoral tunnel drilling techniques, transtibial (TT), transportal (TP), and outside-in (OI) techniques, in anatomic double-bundle ACL reconstruction to clarify advantages and disadvantages of each technique. METHODS: One-hundred and thirty-nine patients underwent primary ACL reconstruction with an autologous semitendinosus tendon in our institution between 2014 and 2016. Thirteen patients were excluded according to the exclusion criteria. Of the 126 patients, 98 patients agreed to be included in this study. Patients were then randomized into three groups according to the femoral tunnel drilling technique; the TT, TP, and OI groups. Femoral and tibial tunnel angles and positions were measured using three-dimensional computed tomography. RESULTS: Of patients who agreed to be included in this study, eight patients (seven in TT and one in OI) were excluded since the femoral tunnel could not be created at the intended position. Eighty-six patients (29 in TT, 29 in TP, and 28 in OI) were included for the analyses. Tunnel angles, as well as tunnel lengths, had significant differences among different techniques depending on each technique's characteristics. In terms of tunnel position, femoral tunnel positions of both the AMB and PLB in the TT group were significantly higher than those in the TP group (AMB: p = 0.003, PLB: p = 0.001), and the PLB tunnel position in the TP group had significantly smaller vaciance than that in the TT group (p = 0.004) and OI group (0.002). CONCLUSIONS: The femoral tunnel positions created by the TT technique were significantly higher, with larger variance, than the TP technique in double-bundle ACL reconstruction, although the positions seemed to be within anatomical footprint. In addition, there were several cases in which femoral tunnels could not be created at the intended position by the TT technique. LEVEL OF EVIDENCE: I.

Risk factors for residual anterolateral rotational instability after double bundle anterior cruciate ligament reconstruction: Evaluation by quantitative assessment of the pivot shift phenomenon using triaxial accelerometer.

BACKGROUND: Exact knowledge of risk factors for residual anterolateral rotatinoal instability (ALRI) after anterior cruciate ligament (ACL) reconstruction is limited. The purpose of this study was to analyse possible risk factors for ALRI after ACL reconstruction. METHODS: Quantitative assessment of the pivot shift phenomenon by measuring tibial acceleration was performed in 46 patients during primary double-bundle ACL reconstructions. The absolute value of the acceleration of the injured knee after provisional fixation of the ACL grafts ('absolute residual acceleration') and the subtraction of the acceleration of the uninjured knee from absolute residual acceleration ('relative residual acceleration') were defined as indicators for residual ALRI. The associations between these indicators and nine candidate risk factors were analysed using univariate and multiple regression analyses. RESULTS: Multiple regression analysis revealed that absolute residual acceleration was positively associated with both preoperative acceleration difference between injured and uninjured knees (ß = 0.469, P < 0.001) and tibial acceleration of the uninjured knee (ß = 0.597, P < 0.001). Relative residual acceleration was also positively associated with preoperative acceleration difference between injured and uninjured knees (ß = 0.446, P< 0.001), but was negatively associated with tibial acceleration of the uninjured knee (ß = -0.763, P < 0.001). CONCLUSIONS: Patients with larger preoperative side-to-side difference of the pivot shift phenomenon have higher risk for both absolute and relative residual ALRIs after ACL reconstruction, whereas patients with larger pivot shift phenomenon in their uninjured knees are at higher risk for absolute residual ALRI but not for relative residual ALRI.

Benefit of subcutaneous patient controlled analgesia after total knee arthroplasty.

PURPOSE: Subcutaneous patient-controlled analgesia (PCA) has been widely used for orthopedic surgeries including total knee arthroplasty (TKA). This study aims to clarify the usefulness of subcutaneous PCA in the early phase after TKA. METHODS: Our subjects consisted of 88 osteoarthritis knee patients who underwent primary TKA, and were classified into two groups: 42 patients received a subcutaneous PCA (containing fentanyl and droleptan) after operation (PCA group), and 46 patients were managed without a subcutaneous PCA (control group). We compared the incidence of side effects for 3 days postoperatively, measuring the number of times patients used adjuvant analgesia and range of motion on day 7 between the two groups. 34 of 42 patients in the PCA group tolerated PCA use until POD 3 (continuation sub-group), while 8 patients could not continue PCA (interruption sub-group). Demographic data of the two sub-groups were compared. RESULTS: The mean number of times adjunctive analgesics were used by the PCA group (3.7 ±â€¯2.2) was significantly less than in the control group (5.4 ±â€¯2.8) (p = 0.0049). There were no significant differences in the frequency of side effects between the two groups. There was no significant difference in range of motion between the two groups. Comparing the continuation and interruption sub-groups, patients over 80 years old were at risk to discontinue a subcutaneous PCA (p = 0.0319, odds ratio 5.4). CONCLUSION: These findings demonstrate that subcutaneous PCA would be a safe postoperative pain regimen for TKA patients, but the effect was not enough to promote early functional recovery. LEVELS OF EVIDENCE: Therapeutic, Level Ⅱ.

The effect of a longitudinal tear of the medial meniscus on medial meniscal extrusion in anterior cruciate ligament injury patients.

PURPOSE: The purpose of this study was to investigate the effect of a longitudinal tear of the medial meniscus (MM) and its meniscal repair on MM extrusion in anterior cruciate ligament (ACL)-injured patients. The hypothesis underlying this study was that a longitudinal tear of the MM is correlated with MM extrusion, and that the extrusion would persist after ACL reconstruction with concomitant MM repair. METHODS: Forty-three ACL-injured patients with a concomitant MM longitudinal tear were included in the MM tear group. Thirty-four solely ACL-injured patients without any meniscal injuries were included in the Control group. Medial meniscus extrusion width (MEW) was measured pre-operatively and three months after surgery on magnetic resonance imaging. RESULTS: Pre-operative MEW in the MM tear group was significantly larger than that in the Control group (MM tear group: 1.5 mm, Control: 0.3 mm, P < 0.001). The MEW change in the MM tear group was significantly greater than that in the Control group three months after operation (MM tear group: 0.8 mm, Control: -0.2 mm, P < 0.001). The number of sutures required for repair was correlated with MEW both pre-operatively and postoperatively in the MM tear group (pre-operative: P = 0.005, R = 0.42, postoperative: P < 0.001, R = 0.54). CONCLUSION: Longitudinal tear of the MM was correlated with MM extrusion and the MM extrusion persisted after ACL reconstruction with concomitant MM repair in the MM tear group. The initial meniscal tear size was directly correlated with the pre-operative MEW. Therefore, meniscal extrusion after longitudinal tears of the medial meniscus should be taken into careful consideration.

Additional Use of Synovial Mesenchymal Stem Cell Transplantation Following Surgical Repair of a Complex Degenerative Tear of the Medial Meniscus of the Knee: A Case Report.

Complex degenerative tears of the medial meniscus in the knee are usually treated using meniscectomy. However, this procedure increases the risk of osteoarthritis, while other treatments aimed at meniscal repair remain challenging due to the high possibility of failure. The use of synovial mesenchymal stem cells (MSCs) is an attractive additional approach for meniscal repair, as these cells have high proliferative and chondrogenic potential. In this case report, we surgically repaired a complex degenerative tear of the medial meniscus and then transplanted autologous synovial MSCs. We evaluated clinical outcomes at 2 years and assessed adverse events. We enrolled patients with clinical symptoms that included a feeling of instability in addition to pain caused by their complex degenerative tears of the medial meniscus. Two weeks after surgical repair of the torn meniscus, autologous synovial MSCs were transplanted onto the menisci of five patients. The total Lysholm knee score, the Knee Injury and Osteoarthritis Outcome Scale scores for "pain," "daily living," "sports activities," and the Numerical Rating Scale were significantly increased after 2 years. Three adverse events, an increase in c-reactive protein, joint effusion, and localized warmth of the knee were recorded, although these could have been due to the meniscal repair surgery. This first-in-human study confirmed that the combination of surgical repair and synovial MSC transplantation improved the clinical symptoms in patients with a complex degenerative tear of the medial meniscus. No adverse events occurred that necessitated treatment discontinuation. These findings will serve as pilot data for a future prospective study.

Cryopreservation in 95% serum with 5% DMSO maintains colony formation and chondrogenic abilities in human synovial mesenchymal stem cells.

BACKGROUND: Synovial mesenchymal stem cells (MSCs) are an attractive cell source for cartilage and meniscus regeneration. The optimum cryopreservation medium has not been determined, but dimethylsulfoxide (DMSO) should be excluded, if possible, because of its toxicity. The purposes of our study were to examine the possible benefits of higher concentrations of serum and the effectiveness of 100% serum (without DMSO) for the cryopreservation of synovial MSCs. METHODS: Human synovium was harvested from the knees of four donors with osteoarthritis during total knee arthroplasty. Synovial MSCs (8 × 105 cells) were suspended in 400 µL medium and used as a Time 0 control. The same number of synovial MSCs was also suspended in 400 µL α-MEM medium containing 10% fetal bovine serum (FBS) (5% DMSO, and 1% antibiotic), 95% FBS (and 5% DMSO), or 100% FBS (no DMSO) and cryopreserved at - 80 °C for 7 days. After thawing, the cell suspensions (1.5 µL; 3 × 103 cells) were cultured in 60 cm2 dishes for 14 days for colony formation assays. Additional 62.5 µL samples of cell suspensions (1.25 × 105 cells) were added to tubes and cultured for 21 days for chondrogenesis assays. RESULTS: Colony numbers were significantly higher in the Time 0 and 95% FBS groups than in the 10% FBS group (n = 24). Colony numbers were much lower in the 100% FBS group than in the other three groups. The cell numbers per dish reflected the colony numbers. Cartilage pellet weights were significantly heavier in the 95% FBS group than in the 10% FBS group, whereas no difference was observed between the Time 0 and the 95% FBS groups (n = 24). No cartilage pellets formed at all in the 100% FBS group. CONCLUSION: Synovial MSCs cryopreserved in 95% FBS with 5% DMSO maintained their colony formation and chondrogenic abilities to the same levels as observed in the cells before cryopreservation. Synovial MSCs cryopreserved in 100% FBS lost their colony formation and chondrogenic abilities.

Contribution of Additional Anterolateral Structure Augmentation to Controlling Pivot Shift in Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Several types of anterolateral structure (ALS) augmentation procedures in anterior cruciate ligament (ACL) reconstruction have been reported. However, information is limited regarding the effect of additional ALS augmentation on rotatory stability in a clinical setting. PURPOSE/HYPOTHESIS: This study aimed to investigate the contribution of additional ALS augmentation in ACL reconstruction in cases with a high risk of residual pivot shift. The 2 hypotheses were as follows. First, additional ALS augmentation would improve rotatory stability as compared with solely reconstructing the ACL. Second, graft tension changes would be different between the ACL and ALS during knee range of motion and against anterior or rotatory loads. STUDY DESIGN: Controlled laboratory study. METHODS: Fifteen patients who met at least 1 of the following criteria were included: (1) revision ACL reconstruction, (2) preoperative high-grade pivot shift, or (3) hyperextended knee. The pivot-shift test was performed preoperatively and during surgery after ACL reconstruction and after additional ALS augmentation with acceleration measurements from a triaxial accelerometer. The tension changes of the ACL and ALS grafts were also measured during knee range of motion and against manual maximum anterior tibial translation, internal rotation, and external rotation. RESULTS: After ACL reconstruction, the pivot-shift acceleration was still greater than that of the uninjured knee. However, additional ALS augmentation further reduced acceleration when compared with ACL reconstruction alone in both primary and revision cases (P < .05 vs preoperative, P < .05 vs ACL). During knee flexion-extension, the tension of the ACL increased as the knee was extended, whereas that of the ALS did not change. Graft tension of the ACL and ALS became higher with internal rotation and lower with external rotation as compared with the neutral position. Tension of the ACL was significantly increased against anterior tibial translational loads, whereas that of the ALS was not. CONCLUSION: Additional ALS augmentation further improved the rotatory stability during ACL reconstruction in patients with a high risk of residual pivot shift at the time of surgery. Significant differences in graft tension changes were also observed between the ACL and ALS against different loads. Additional ALS augmentation may be considered to eliminate the pivot shift in patients with a high risk of residual pivot shift.

Comparison of High-Hydrostatic-Pressure Decellularized Versus Freeze-Thawed Porcine Menisci.

The meniscus functions as a load distributor and secondary stabilizer in the knee, and the loss of the meniscus increases the risk of osteoarthritis. Freeze-thawed menisci are used in clinical practice to replace defective menisci; however, the disadvantages of freeze-thawed tissues include disease transmission and immune rejection. In this study, we decellularized menisci using high hydrostatic pressure (HHP) and compared the decellularized menisci with freeze-thawed menisci. Porcine menisci were either pressurized at 1,000 MPa for 10 min and then washed with DNase solution or frozen at -80°C for 2 days and thawed. These menisci then underwent in vitro histological, biochemical, and biomechanical comparisons with native menisci. The HHP-treated and freeze-thawed menisci were also subcutaneously implanted in a pig, and later harvested for histological analysis. The numbers of histologically detected cells were significantly lower and the amount of biochemically detected DNA was approximately 100-fold lower in HHP-treated than in native and freeze-thawed menisci. The compression strength of the HHP-decellularized menisci was decreased after 1 and 50 cycles at 20% strain but was unchanged in the freeze-thawed menisci. After implantation, the numbers of multinucleated giant cells were significantly lower around the HHP-treated menisci than around the freeze-thawed menisci. Recellularization of the HHP-decellularized menisci was confirmed. Thus, although the HHP-decellularized menisci were mechanically inferior to the freeze-thawed meniscus in vitro, they were immunologically superior. Our study is the first to demonstrate the use of HHP for decellularization of the meniscus. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2466-2475, 2019.

Petaloid recombinant peptide enhances in vitro cartilage formation by synovial mesenchymal stem cells.

In vitro chondrogenesis of mesenchymal stem cells (MSCs) mimics in vivo chondrogenesis of MSCs. However, the size of the cartilage pellets that can be attained in vitro is limited by current methods; therefore, some modifications are required to obtain larger pellets. Petaloid pieces of recombinant peptide (petaloid RCP) have the advantage of creating spaces between cells in culture. The RCP used here is based on the alpha-1 sequence of human collagen type I and contains 12 Arg-Gly-Asp motifs. We examined the effect and mechanisms of adding petaloid RCP on the in vitro chondrogenesis of human synovial MSCs by culturing 125k cells with or without 0.125 mg petaloid RCP in chondrogenic medium for 21 days. The cartilage pellets were sequentially analyzed by weight, sulfated glycosaminoglycan content, DNA retention, and histology. Petaloid RCP significantly increased the weight of the cartilage pellets: The petaloid RCP group weighed 7.7 ± 1.2 mg (n = 108), whereas the control group weighed 5.3 ± 1.6 mg. Sulfated glycosaminoglycan and DNA contents were significantly higher in the petaloid RCP group than in the control group. Light and transmission electron microscopy images showed that the petaloid RCP formed the framework of the pellet at day 1, the framework was broken by production of cartilage matrix by the synovial MSCs at day 7, and the cartilage pellet grew larger, with diffuse petaloid RCP remaining, at day 21. Therefore, petaloid RCP formed a framework for the pellet, maintained a higher cell number, and promoted in vitro cartilage formation of synovial MSCs. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res 37:1350-1357, 2019.

Projected Cartilage Area Ratio Determined by 3-Dimensional MRI Analysis: Validation of a Novel Technique to Evaluate Articular Cartilage.

We have developed 3-dimensional (3D) magnetic resonance imaging (MRI) analysis software that allows measurement of the projected cartilage area ratio with a particular thickness intended to allow quantitation of the cartilage in the knee. Our aims in this study were to validate the projected cartilage area ratio in both pig and human knees and to examine the ratio in patients reporting knee pain. METHODS: After 3D MRI reconstruction, the femoral cartilage was projected onto a flat surface. The projected cartilage area was determined in pig knees using our 3D MRI analysis software, and was compared with the area obtained with other software. The projected cartilage area ratio (for cartilage thickness ≥1.5 mm) at 4 segments was also validated in human knees. Finally, changes in the projected cartilage area ratio were examined in 8 patients with knee pain who had undergone 2 MR images at 3 to 21-month intervals. RESULTS: The projected cartilage areas determined with our 3D MRI analysis software were validated in pig knees. The projected cartilage area ratio at each segment in human knees had an intraclass correlation coefficient (ICC) of 0.87 to 0.99 (n = 16) between readers and 0.76 to 0.99 (n = 20) between measurements on repeat MR images. The projected cartilage area ratio (for cartilage thickness ≥1.5 mm) at the most affected segment in 8 human patients significantly decreased between the pairs of MR images obtained at intervals of 3 to 21 months. CONCLUSIONS: We proposed a novel evaluation method using 3D MRI to quantify the amount of cartilage in the knee. This method had a low measurement error in both pig and human knees. CLINICAL RELEVANCE: The projected cartilage area ratio based on a particular thickness may serve as a sensitive method for assessing changes in cartilage over time.