Janus Membranes Patch Achieves High-Quality Tendon Repair: Inhibiting Exogenous Healing and Promoting Endogenous Healing.

The imbalance between endogenous and exogenous healing is the fundamental reason for the poor tendon healing. In this study, a Janus patch was developed to promote endogenous healing and inhibit exogenous healing, leading to improved tendon repair. The upper layer of the patch is a poly(dl-lactide-co-glycolide)/polycaprolactone (PLGA/PCL) nanomembrane (PMCP-NM) modified with poly(2-methylacryloxyethyl phosphocholine) (PMPC), which created a lubricated and antifouling surface, preventing cell invasion and mechanical activation. The lower layer is a PLGA/PCL fiber membrane loaded with fibrin (Fb) (Fb-NM), serving as a temporary chemotactic scaffold to regulate the regenerative microenvironment. In vitro, the Janus patch effectively reduced 92.41% cell adhesion and 79.89% motion friction. In vivo, the patch inhibited tendon adhesion through the TGF-ß/Smad signaling pathway and promoted tendon maturation. This Janus patch is expected to provide a practical basis and theoretical guidance for high-quality soft tissue repair.

Healthy Tendon Stem Cell-Derived Exosomes Promote Tendon-To-Bone Healing of Aged Chronic Rotator Cuff Tears by Breaking the Positive-Feedback Cross-Talk between Senescent Tendon Stem Cells and Macrophages through the Modulation of Macrophage Polarization.

The re-tear rate of rotator cuff tears (RCT) after surgical repair is high, especially in aged patients with chronic tears. Senescent tendon stem cells (s-TSCs) generally exist in aged and chronically torn rotator cuff tendons and are closely associated with impaired tendon-to-bone healing results. The present study found a positive feedback cross-talk between s-TSCs and macrophages. The conditioned medium (CM) from s-STCs can promote macrophage polarization mainly toward the M1 phenotype, whose CM reciprocally accelerated further s-TSC senescence. Additional healthy tendon stem-cells derived exosomes (h-TSC-Exos) can break this positive feedback cross-talk by skewing macrophage polarization from the M1 phenotype to the M2 phenotype, attenuating s-TSCs senescence. S-TSC senescence acceleration or attenuation effects induced by M1 or M2 macrophages are associated with the inhibition or activation of the bone morphogenetic protein 4 signaling pathway following RNA sequencing analysis. Using an aged-chronic rotator cuff tear rat model, it is found that h-TSC-Exos can shift the microenvironment in the tendon-to-bone interface from a pro-inflammatory to an anti-inflammatory type at the acute postoperative stage and improve the tendon-to-bone healing results, which are associated with the rejuvenated s-TSCs. Therefore, this study proposed a potential strategy to improve the healing of aged chronic RCT.

Arthroscopic medial patellofemoral ligament reconstruction with polyethylene suture combined with medial retinaculum plication for the treatment of acute patellar dislocation in young and middle-aged patients with a follow-up of at least 2 years.

PURPOSE: The purpose of this study was to propose a surgical technique for arthroscopic medial patellofemoral ligament (MPFL) reconstruction with polyethylene suture combined with medial retinaculum plication and to evaluate the efficacy of this surgical technique in the treatment of acute patellar dislocation. METHODS: Clinical data of patients with acute patellar dislocations treated with arthroscopic MPFL reconstruction with polyethylene tape (FiberTape) combined with medial support band compression were analyzed retrospectively from January 2018 to January 2021. The mean age of the patients was 25.15 ± 4.66 years; the mean follow-up time was 27.5 (24-36) months. Clinical evaluation consisted of apprehension test results, patellar extrapolation test results, Lysholm score, Kujala score, and IKDC score, the Patellar lateral shift distance and patellar tilt angle (PTA) measured by CT scan. RESULTS: All patients had no recurrent patellar dislocation or subluxation after surgery, and the apprehension test was negative. In all patients, the Kujala score (36.0 ± 9.9 vs. 98.2 ± 3.1), the IKDC score (48.6 ± 7.0 vs. 90.6 ± 4.4) and the Lysholm score (32.8 ± 10.4 vs. 96.7 ± 3.1) had improved at the 24-month follow up (P < 0.05). In addition, PTA was significantly lower at the 12-month follow-up and 24-giving-month follow-up compared to the preoperative period (P < 0.05, Table 2). The patellar lateral shift distance decreased from 14.94 ± 6.11 mm preoperatively to 3.00 ± 1.40 mm (12-month follow up) and 3.26 ± 1.37 mm (24-month follow up), respectively. CONCLUSION: Arthroscopic MPFL reconstruction with polyethylene suture combined with medial retinaculum plication is a safe and reliable surgical technique for the treatment of acute patellar dislocation in young and middle-aged patients. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

Double-Level Knee Derotational Osteotomy Yields Better Postoperative Outcomes Than Tibial Tubercle Transfer Combined With Medial Patellofemoral Ligament Reconstruction in Patients With Recurrent Patellar Instability and Severe Malrotation.

PURPOSE: To assess the postoperative outcomes of double-level knee derotational osteotomy (KDRO) combined with medial patellofemoral ligament reconstruction (MPFLR) and to compare it with tibial tuber transfer (TTT) and MPFLR without derotational osteotomy in patients with recurrent patellar instability and a marked torsional deformity. METHODS: From March 2020 to December 2021, patients with torsion deformity (combined femoral torsion [FT] and tibial torsion [TTn] ≥30°) were retrospectively included. The minimum follow-up time was 18 months. Patients who received KDRO and MPFLR were categorized as the KDRO group and patients who received a combined TTT and MPFLR were categorized as the control group. Preoperative and postoperative clinical symptoms, patient-reported outcomes (Kujala, visual analog scale, Lysholm, International Knee Documentation Committee, Tegner, and Knee Injury and Osteoarthritis Outcome scores), and imaging parameters (FT, TTn, patellar height, femoral trochlear dysplasia, congruence angle, patellar tilt angle, lateral patellar angle, lateral patellar translation, and tibial tubercle-trochlear groove distance) were analyzed. RESULTS: In all, 36 patients were included with 18 in KDRO group and 18 in control group. The mean follow-up time was 30 (range 21-39) months. At the latest follow-up, no patient experienced redislocation in either group. Except for the FT and TTn in the control group, postoperative imaging parameters were significantly reduced to the normal range. KDRO group had a lower patellar tilt angle (P = .043, effect size 0.64). All clinical scores in both groups significantly improved postoperatively. The KDRO group had better functional scores than control group except the KOOS daily living activities subscore and the KOOS sports and recreation subscore. More patients in the KDRO group met the minimal clinically important difference for most patient-reported outcomes than the control group. Eight patients (44%) in the control group complained of postoperative anterior knee pain, compared with 1 patient (6%) in the KDRO group (P = .018). CONCLUSIONS: KDRO combined with MPFLR was associated with better postoperative outcomes than TTT combined with MPFLR in patients with recurrent patellar instability and a torsion deformity. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Biomechanical Analysis Reveals Shoulder Instability With Bipolar Bone Loss Is Best Treated With Dynamic Anterior Stabilization for On-Track Lesions and With Remplissage for Off-Track Lesions.

PURPOSE: To compare the biomechanical effects of augmenting Bankart repair (BR) with either remplissage or dynamic anterior stabilization (DAS) in the treatment of anterior shoulder instability with on-track or off-track bipolar bone loss. METHODS: Eight fresh-frozen cadaveric shoulders were tested at 60° of glenohumeral abduction in the intact, injury, and repair conditions. Injury conditions included 15% glenoid bone loss with an on-track or off-track Hill-Sachs lesion as previously recommended. Repair conditions included isolated BR, BR with remplissage, and BR with DAS (long head of biceps transfer). The glenohumeral stability was assessed by measuring the anterior translation under 0, 10, 20, 30, 40, 50 N load and maximum load without causing instability at mid-range (60°) and end-range (90°) external rotation (ER). Maximum range of motion (ROM) was measured by applying a 2.2-N·m torque in passive ER and internal rotation. RESULTS: Isolated BR failed to restore native glenohumeral stability in both on-track and off-track bipolar bone loss models. Both remplissage and DAS significantly decreased the anterior instability in the bipolar bone loss models, showing better restoration than the isolated BR. In the on-track lesions, DAS successfully restored native glenohumeral stability and mobility, whereas remplissage significantly decreased anterior translation without load (-2.12 ± 1.07 mm at 90° ER, P = .003; -1.98 ± 1.23 mm at 60° ER, P = .015). In the off-track lesions, remplissage restored native glenohumeral stability but led to significant ROM limitation (-8.6° ± 2.3° for internal rotation, P < .001; -13.9° ± 6.2° for ER, P = .003), whereas DAS failed to restore native stability at 90° ER regarding the increased anterior translation under 50 N (4.10 ± 1.53 mm, P < .001) and decreased maximum load (-13.8 ± 9.2 N, P = .021). CONCLUSIONS: At time-zero, both remplissage and DAS significantly reduced residual anterior instability compared with isolated BR in the bipolar bone loss models and restored the native glenohumeral stability under most translational loads. However, remplissage could decrease the anterior translation without load for on-track lesions and may restrict ROM for off-track lesions, whereas DAS failed to restore native stability under high translational loads for off-track lesions. CLINICAL RELEVANCE: DAS could be recommended to treat on-track bipolar bone loss with less biomechanical adverse effects, whereas remplissage might be the preferred procedure to address off-track bipolar bone loss for better stability.

Impact of sex and age on the lateralisation of the tibial tubercle in normal paediatric and adolescent populations.

PURPOSE: Numerous methods have been proposed to characterise tubercle lateralisation. However, their normal values and related changes remain unclear. Accordingly, it was aimed to determine the potential sex and age effects and determined the optimal individualised method of diagnosing lateralisation of the tibial tubercle in patients with recurrent patellar dislocation (RPD). METHODS: Measurements included the tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance and tibial tubercle lateralisation (TTL); and the proximal tibial width (PTW), trochlear width (TW) and trochlear dysplasia index (TDI), for adjustment. A two-way analysis of variance was used to determine the effect of age, sex and their interaction within the normal group. When the age effect was statistically significant, a nonlinear regression was created. Areas under the receiver-operating characteristic curve (AUCs) were calculated to assess diagnostic accuracy. RESULTS: A total of 277 normal participants (mean [SD] age, 13.5 [2.6] years; 125 [45.1%] female) and 227 patients with RPD (mean [SD] age, 13.5 [2.6] years; 161 [58.1%] female) were analysed. It was found that in the normal group, in patients aged 7-10, TT-PCL distance (p = 0.006), TTL (p = 0.007) and TT-PCL/PTW (p < 0.001) were significantly larger in females than in males. A significant sex effect was also detected on TT-TG/TW (p = 0.014). TT-TG distance, TT-PCL distance, TTL and TT-PCL/PTW (in male patients) approached an established normal adult value of 12.3 mm, 20.9 mm, 0.64 and 0.28, respectively, with increasing age (p < 0.001). The AUC was greater for TT-TG/TDI and TT-TG/TW (p ≤ 0.01) and TT-TG/TDI outperformed TT-TG/TW in patients aged 15-18 (p = 0.004). CONCLUSIONS: Tubercle lateralisation increased with age and was affected by sex, with the exception of TT-TG distance and TT-TG/TDI. TT-TG/TDI is the optimal method of diagnosing a lateralized tibial tubercle in patients with RPD. These findings assist with the evaluation of tubercle lateralisation in that they provide a proper protocol for paediatric and adolescent populations with RPD; and thus, will help determine whether medial tubercle transfer should be included among the tailored surgical procedures considered for the treatment of patients with RPD. LEVEL OF EVIDENCE: Level III.

Anatomic double-bundle transtibial anterior cruciate ligament reconstruction restores graft length changes but leads to larger graft bending angles.

PURPOSE: The purpose of this study was to evaluate the femoral tunnel position using a modified anatomic transtibial (TT) double-bundle anterior cruciate ligament reconstruction (DBACLR) and to investigate the knee kinematics, graft length and graft bending angle following DBACLR. METHODS: Ten patients who underwent DBACLR using the modified TT technique were included in the study. All patients performed a single-legged lunge under a dual fluoroscopic imaging system to assess the 6 degrees of freedom tibiofemoral kinematics. Femoral tunnel position was evaluated via postoperative three-dimensional (3D) computed tomography. The area centroids of anteromedial (AM) and posterolateral (PL) bundles were determined on 3D knee models. The lengths of AM and PL bundles, as well as graft bending angle at the femoral tunnel aperture, were measured by created virtual fibres. RESULTS: The reconstructed knee rotated more externally compared with the contralateral knee between 0° and 60° (p ≤ 0.049). There is no significant difference in the length change of AM bundle (n.s.) and PL bundle (n.s.) between the two sides from 0° to 120° during the lunge motion. The maximum graft bending angle at the femoral tunnel aperture occurred at 0° of knee flexion, with the AM graft bending angle was 72.6° ± 9.0° and the PL graft bending angle was 90.3° ± 9.7°. CONCLUSION: The modified TT technique used in this study could achieve anatomical ACL reconstruction, restoring graft length change patterns compared to contralateral knees. However, residual rotational instability of the reconstructed knee was observed after DBACLR, despite achieving anatomic tunnel placement. Therefore, double-bundle reconstruction may not sufficiently address the persistent rotational instability of the knee. Additionally, larger graft bending angles at the femoral tunnel aperture were found with the modified TT technique. Therefore, further improvement to the TT technique should focus on reducing the graft's curvature while maintaining the anatomical properties of the knee joint. The findings of this study highlight the need for improved surgical techniques to address residual rotational instability and optimise graft curvature. These improvements are crucial for enhancing patient outcomes and long-term joint function following ACL reconstruction. LEVELS OF EVIDENCE: Level II.

Immunomodulatory Activity and Its Mechanisms of Two Polysaccharides from Poria cocos.

Polyporaceae is an important fungal family that has been a source of natural products with a range of pharmaceutical activities in China. In our previous study, two polysaccharides, PCWPW and PCWPS, with significant antioxidant and antidepressant activity were obtained from Poria cocos. In this study, we evaluated their potential molecular mechanisms in the immunomodulation of macrophages. PCWPW and PCWPS were characterized by GC-MS analysis to contain 1,3-linked Glcp. ELISA assays results demonstrated that the secretion of TNF-α was significantly enhanced by PCWPW/PCWPS. RNA-seq data demonstrated that PCWPS treatment modulated the expression of immune-related genes in macrophages, which was further confirmed by RT-qPCR assays. The activation of TNF-α secretion was found to be mannose receptor (MR) dependent and suppressed by MR inhibitor pretreatment. Moreover, the amount of TNF-α cytokine secretion in PCWPW/PCWPS-induced RAW264.7 cells was decreased when pretreated with NF-κB or MAPK signaling pathway inhibitors. Collectively, our results suggested that PCWPW and PCWPS possessed immunomodulatory activity that regulates TNF-α expression through the NF-κB/MAPK signaling pathway by binding to mannose receptors. Therefore, PCWPW and PCWPS isolated from Poria cocos have potential as drug candidates for immune-related disease treatment.

Application study of surgical instruments information management system in sports medicine specialty.

The management of surgical instruments is related to the safety and efficiency of surgical operations, and a surgical instruments information management system (SIIMS) has been developed. The aim of the current study is to explore the application value of the SIIMS in sports medicine specialty. A set of self-developed SIIMS for sports medicine surgeries was applied to the study. The application value of the SIIMS was verified by comparing the safety and efficiency of instrument manipulation before and after its application, with instrument accidents, instrument repair rate, instrument scrap rate and instrument use efficiency as indicators. Through the application of the SIIMS, the incidence of surgical instrument accidents decreased from 3.7 times to 1.8 times (P = 0.02), the number of instrument repair decreased from 7.7 times to 2.9 times (P = 0.00), and the number of scrapped instruments decreased from 5.1 to 2.3 (P = 0.03), when referred to per thousand operations. Before and after the application of the SIIMS, the average instrument use efficiency was 74.0% ± 3.3% and 88.2% ± 4.4%, respectively, with statistically significant difference (P = 0.00). The application of the SIIMS in sports medicine specialty is helpful to the fine management of surgical instruments, improve surgical safety and instrument use efficiency.

Longitudinal Changes in Overall 3D Supraspinatus Muscle Volume and Intramuscular Fatty Infiltration After Arthroscopic Rotator Cuff Repair.

BACKGROUND: There is considerable debate regarding the longitudinal changes in overall rotator cuff (RC) muscle atrophy and intramuscular fatty infiltration (FI) following RC repair. We analyzed the longitudinal changes in overall 3D supraspinatus muscle volume and intramuscular FI (3D FI) to determine the effect of tear size and repair integrity on 3D muscle volume and intramuscular FI. METHODS: Forty-seven patients who underwent arthroscopic RC repair and had 6-point Dixon shoulder magnetic resonance imaging (MRI) preoperatively and 3 and 12 months postoperatively were enrolled. The 3D supraspinatus muscle volume and intramuscular FI were calculated at the 3 time points, and their changes over time were evaluated in the entire cohort as well as according to tear size and repair integrity. The agreement of the difference between time points among the patients was assessed by Bland-Altman analysis. RESULTS: In the cohort as a whole, there were no significant longitudinal changes in the 3D supraspinatus volume (19.65 ± 7.26 to 19.48 ± 7.46 cm 3 , p = 0.911) or 3D FI (17.18% ± 8.85% to 17.30% ± 9.18%, p = 0.977) from preoperatively to the final 12-month time point, overall and in the tear size and repair integrity subgroups. The 3D supraspinatus volume was significantly decreased at 3 months (17.39 ± 6.12 cm 3 , p < 0.001) but then increased again by 12 months (p < 0.001), reaching a value similar to the preoperative level. The 3D FI had a small increase at 3 months (18.18% ± 9.65%, p = 0.097) but subsequently decreased slightly again (p = 0.211), such that there were no significant longitudinal changes. The differences in the 3D supraspinatus volume and FI between these time points showed high agreement among patients. CONCLUSIONS: The overall 3D supraspinatus volume and 3D FI showed no longitudinal change between the preoperative baseline and the 12-month follow-up after arthroscopic RC repair. Tear size and repair integrity had no impact on the longitudinal patterns of muscle volume and intramuscular FI changes. The 3D supraspinatus volume decreased during the first 3 months but recovered to baseline at 12 months postoperatively; 3D FI was relatively stable throughout the 12 months of follow-up after repair. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Robotic-assisted anatomic anterior cruciate ligament reconstruction: a comparative analysis of modified transtibial and anteromedial portal techniques in cadaveric knees.

Introduction: This study employed surgical robot to perform anatomic single-bundle reconstruction using the modified transtibial (TT) technique and anteromedial (AM) portal technique. The purpose was to directly compare tunnel and graft characteristics of the two techniques. Methods: Eight cadaveric knees without ligament injury were used in the study. The modified TT and AM portal technique were both conducted under surgical robotic system. Postoperative data acquisition of the tunnel and graft characteristics included tibial tunnel position, tunnel angle, tunnel length and femoral tunnel-graft angle. Results: The mean tibial tunnel length of the modified TT technique was significantly shorter than in the AM portal technique (p < 0.001). The mean length of the femoral tunnel was significantly longer for the modified TT technique than for the AM portal technique (p < 0.001). The mean coronal angle of the tibial tunnel was significantly lower for the modified TT technique than for the AM portal technique (p < 0.001). The mean coronal angle of the femoral tunnel was significantly lower for the AM portal technique than for the modified TT technique (p < 0.001). The AM portal technique resulted in a graft bending angle that was significantly more angulated in the coronal (p < 0.001) and the sagittal planes (p < 0.001) compared with the modified TT technique. Discussion: Comparison of the preoperative planning and postoperative femoral tunnel positions showed that the mean difference of the tunnel position was 1.8 ± 0.4 mm. It suggested that the surgical navigation robot could make predictable tunnel position with high accuracy. The findings may support that the modified TT technique has benefits on femoral tunnel length and obliquity compared with AM portal technique. The modified TT technique showed a larger femoral tunnel angle in the coronal plane than the AM portal technique. Compared with the modified TT technique, the more horizontal trajectory of the femoral tunnel in the AM portal technique creates a shorter femoral tunnel length and a more acute graft bending angle.

Optimal tibial tunnel angulation for anatomical anterior cruciate ligament reconstruction using transtibial technique.

Numerous studies have suggested that the primary cause of failure in transtibial anterior cruciate ligament reconstruction (ACLR) is often attributed to non-anatomical placement of the bone tunnels, typically resulting from improper tibial guidance. We aimed to establish the optimal tibial tunnel angle for anatomical ACLR by adapting the transtibial (TT) technique. Additionally, we aimed to assess graft bending angle (GBA) and length changes during in vivo dynamic flexion of the knee. Twenty knee joints underwent a CT scan and dual fluoroscopic imaging system (DFIS) to reproduce relative knee position during dynamic flexion. For the single-legged lunge, subjects began in a natural standing position and flexed the right knee beyond 90° When performing the lunge task, the subject supported the body weight on the right leg, while the left leg was used to keep the balance. The tibial and femoral tunnels were established on each knee using a modified TT technique for single-bundle ACLR. The tibial tunnel angulation to the tibial axis and the sagittal plane were measured. Considering that ACL injuries tend to occur at low knee flexion angles, GBA and graft length were measured between 0° and 90° of flexion in this study. The tibial tunnel angulated the sagittal plane at 42.8° ± 3.4°, and angulated the tibial axis at 45.3° ± 5.1° The GBA was 0° at 90° flexion of the knee and increased substantially to 76.4 ± 5.5° at 0° flexion. The GBA significantly increased with the knee extending from 90° to 0° (p < 0.001). The ACL length was 30.2mm±3.0 mm at 0° flexion and decreased to 27.5mm ± 2.8 mm at 90° flexion (p = 0.072). To achieve anatomic single-bundle ACLR, the optimal tibial tunnel should be angulated at approximately 43° to the sagittal plane and approximately 45° to the tibial axis using the modified TT technique. What's more, anatomical TT ACLR resulted in comparable GBA and a relatively constant ACL length from 0° to 90° of flexion. These findings provide theoretical support for the clinical application and the promotion of the current modified TT technique with the assistance of a robot to achieve anatomical ACLR.

Comparing Ultrasound and MRI Evaluations of the Hamstring Tendon for Predicting Autograft Size in Anterior Cruciate Ligament Reconstruction.

Background: Adequate graft size and length are crucial factors in anterior cruciate ligament (ACL) reconstruction. Accurate identification of patients who may be at risk for an insufficient length or size of the hamstring tendon (HT) can aid surgeons in preoperative planning. Purpose: To evaluate whether magnetic resonance imaging (MRI) or ultrasound could more accurately predict the size of the semitendinosus tendon (ST) and gracilis tendon (GT) and to investigate the correlation between anthropometry, graft size, and imaging measurements to find a predictive formula. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Included in the study were 36 patients who underwent ACL reconstruction with HT autograft at our institution between July 2021 and May 2022. Anthropometric data and MRI and ultrasound measurements were collected preoperatively. The length and diameter of the HT were recorded intraoperatively. Correlations between anthropometry, graft size, and imaging measurements were analyzed. Linear regression analysis was performed to construct a prediction formula. Results: The intraoperative graft diameters of the ST and GT were weakly to moderately associated with their cross-sectional areas as measured by MRI and ultrasound. MRI and ultrasound interpreted 11.9% to 15.7% and 18.4% to 41.7% of the variation in the graft diameter of the HT, with an accuracy of 50.0% to 55.6% and 69.4% to 86.1%, respectively. The intraoperative lengths of the ST and GT were both associated with patient height and tendon lengths as measured by ultrasound. Additionally, intraoperative GT length was associated with patient weight. Four formulas combining relevant anthropometric parameters and imaging measurements were calculated from multilinear regression analysis, explaining up to 46.3% of the variance in the size of HT. Conclusion: Ultrasound and MRI alone showed limited ability to predict the graft diameter of the ST and GT, while ultrasound could more accurately predict the graft size than MRI. Among the different anthropometric variables, height was the most influential in predicting tendon length.

Ensemble Algorithm for Risk Prediction of Clinical Failure After Anterior Cruciate Ligament Reconstruction.

Background: Patient-specific risk profiles of clinical failure after anterior cruciate ligament reconstruction (ACLR) are meaningful for preoperative surgical planning and postoperative rehabilitation guidance. Purpose: To create an ensemble algorithm machine learning (ML) model and ML-based web-based tool that can predict the patient-specific risk of clinical failure after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 432 patients (mean age, 26.8 ± 8.4 years; 74.1% male) who underwent anatomic double-bundle ACLR with hamstring tendon autograft between January 2010 and February 2019. The primary outcome was the probability of clinical failure at a minimum 2-year follow-up. The authors included 24 independent variables for feature selection and model development. The data set was split randomly into training sets (75%) and test sets (25%). Models were built using 4 ML algorithms: extreme gradient boosting, random forest, light gradient boosting machine, and adaptive boosting. In addition, a weighted-average voting (WAV) ensemble model was constructed using the ensemble-voting technique to predict clinical failure after ACLR. Concordance (area under the receiver operating characteristic curve [AUC]), calibration, and decision curve analysis were used to evaluate predictive performances of the 5 models. Results: Clinical failure occurred in 73 of the 432 patients (16.9%). The 8 most important predictors for clinical failure were follow-up period, high-grade preoperative knee laxity, time from injury to ACLR, participation in competitive sports, posterior tibial slope, graft diameter, age at surgery, and medial meniscus resection. The WAV ensemble algorithm achieved the best predictive performance based on concordance (AUC, 0.9139), calibration (calibration intercept, -0.1806; calibration slope, 1.2794; Brier score, 0.0888), and decision curve analysis (greatest net benefits) and was used to develop an web-based application to predict a patient's clinical failure risk of ACLR. Conclusion: The WAV ensemble algorithm was able to accurately predict patient-specific risk of clinical failure after ACLR. Clinicians and patients can use the web-based application during preoperative consultation to understand individual prediction outcomes.

3-Dimensional Bioprinting of a Tendon Stem Cell-Derived Exosomes Loaded Scaffold to Bridge the Unrepairable Massive Rotator Cuff Tear.

BACKGROUND: Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues. PURPOSE: To fabricate a tendon stem cell-derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)-based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively. RESULTS: TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL. CONCLUSION: TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation. CLINICAL RELEVANCE: The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects.

Clinical and Radiological Outcomes After Combined ACL and MPFL Reconstruction Versus Isolated ACL Reconstruction for ACL Injury With Patellar Instability.

BACKGROUND: An anterior cruciate ligament (ACL) injury accompanied by patellar instability (PI) is a topic that has gained orthopaedic surgeons' attention recently. Untreated PI is reportedly associated with worse clinical outcomes after isolated ACL reconstruction (ACLR) in patients after an ACL injury with PI. Nevertheless, the appropriate surgical approach and its long-term therapeutic effects in these patients remain unclear. PURPOSE: (1) To compare the clinical and radiological outcomes between isolated ACLR (iACLR) and combined ACLR and medial patellofemoral ligament reconstruction (cAMR) in patients after an ACL injury with PI and (2) to explore the correlations between these 2 procedures and clinical and radiological outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 106 patients diagnosed with an ACL injury accompanied by PI between January 2016 and April 2021 were analyzed in this study. There were 34 patients excluded because of missing postoperative radiological data. Among the remaining 72 patients, 34 patients underwent iACLR, while 38 patients underwent cAMR. Demographic characteristics, intraoperative findings, and patient-reported outcomes (Lysholm score, subjective International Knee Documentation Committee score, and Tegner activity score) were prospectively collected. Patellar alignment parameters and worsening patellofemoral osteoarthritis (PFOA) features (evaluated with the modified Whole-Organ Magnetic Resonance Imaging Score) were analyzed longitudinally on magnetic resonance imaging. The Kujala score was used to evaluate the functional recovery of the patellofemoral joint, and redislocations of the patella were prospectively recorded. Finally, multivariate logistic regression analysis was used to explore the correlations between these 2 procedures and clinical (not achieving the minimal detectable change [MDC] for the Lysholm score) and radiological (worsening PFOA features) outcomes. RESULTS: The mean follow-up duration was 28.9 ± 6.2 and 27.1 ± 6.8 months for the iACLR and cAMR groups, respectively (P = .231). Significantly higher Lysholm scores (88.3 ± 9.9 vs 82.1 ± 11.1, respectively; P = .016) and subjective International Knee Documentation Committee scores (83.6 ± 11.9 vs 78.3 ± 10.2, respectively; P = .046) were detected in the cAMR group compared with the iACLR group postoperatively. The rates of return to preinjury sports were 20.6% and 44.7% in the iACLR and cAMR groups, respectively (difference, 24.1% [95% CI, 3.3%-45.0%]; P = .030). Moreover, the rates of worsening PFOA features were 44.1% and 18.4% in the iACLR and cAMR groups, respectively (difference, 25.7% [95% CI, 4.9%-46.4%]; P = .018). In addition, significantly higher Kujala scores (87.9 ± 11.3 vs 80.1 ± 12.0, respectively; P = .006), lower redislocation rates (0.0% vs 11.8%, respectively; difference, 11.8% [95% CI, 0.9%-22.6%]; P = .045), and significantly better patellar alignment were detected in the cAMR group compared with the iACLR group postoperatively. Furthermore, multivariate logistic regression analysis determined that iACLR and partial lateral meniscectomy were significantly correlated with not achieving the MDC for the Lysholm score and worsening PFOA features in our study population. CONCLUSION: In patients after an ACL injury with PI, cAMR yielded better clinical and radiological outcomes compared with iACLR, with better patellar stability and a lower proportion of worsening PFOA features. Furthermore, not achieving the MDC for the Lysholm score and worsening PFOA features were significantly correlated with iACLR and partial lateral meniscectomy. Our study suggests that cAMR may be a more appropriate procedure for patients after an ACL injury with PI, which warrants further high-level clinical evidence.

Durable immunomodulatory hierarchical patch for rotator cuff repairing.

Degradable rotator cuff patches, followed over five years, have been observed to exhibit high re-tear rates exceeding 50%, which is attributed to the inability of degradable polymers alone to restore the post-rotator cuff tear (RCT) inflammatory niche. Herein, poly(ester-ferulic acid-urethane)urea (PEFUU) was developed, featuring prolonged anti-inflammatory functionality, achieved by the integration of ferulic acid (FA) into the polyurethane repeating units. PEFUU stably releases FA in vitro, reversing the inflammatory niche produced by M1 macrophages and restoring the directed differentiation of stem cells. Utilizing PEFUU, hierarchical composite nanofiber patch (HCNP) was fabricated, simulating the natural microstructure of the tendon-to-bone interface with an aligned-random alignment. The incorporation of enzymatic hydrolysate derived from decellularized Wharton jelly tissue into the random layer could further enhance cartilage regeneration at the tendon-to-bone interface. Via rat RCT repairing model, HCNP possessing prolonged anti-inflammatory properties uniquely facilitated physiological healing at the tendon-to-bone interface's microstructure. The alignment of fibers was restored, and histologically, the characteristic tripartite distribution of collagen I - collagen II - collagen I was achieved. This study offers a universal approach to the functionalization of degradable polymers and provides a foundational reference for their future applications in promoting the in vivo regeneration of musculoskeletal tissues.

A Colorimetric RT-LAMP Assay for Rapid Detection of Soybean mosaic Virus SC15.

Soybean mosaic virus (SMV) represents one of the most devastating viral diseases affecting soybeans worldwide. Among its strains, SMV-SC15 is notable for its virulence, predominance, and widespread occurrence. Rapid and on-site diagnosis is important for controlling the spread of SMV-SC15. In this study, we proposed a colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of SMV-SC15 using three color indicators for visual interpretation: Neutral Red (N-Red), Bromothymol Blue (BTB), and SYBR Green I. The SMV-SC15 in the soybean tissue was detected with remarkable sensitivity and specificity within 30 min, achieving a detection limit as low as 10-4 ng/µL. 200 soybean leaf samples from the field were analyzed by the colorimetric RT-LAMP assays, holding significant potential for rapid screening of SMV-SC15-resistant cultivars, thereby contributing to effective SMV control.

WGCNA Reveals Hub Genes and Key Gene Regulatory Pathways of the Response of Soybean to Infection by Soybean mosaic virus.

Soybean mosaic virus (SMV) is one of the main pathogens that can negatively affect soybean production and quality. To study the gene regulatory network of soybeans in response to SMV SC15, the resistant line X149 and susceptible line X97 were subjected to transcriptome analysis at 0, 2, 8, 12, 24, and 48 h post-inoculation (hpi). Differential expression analysis revealed that 10,190 differentially expressed genes (DEGs) responded to SC15 infection. Weighted gene co-expression network analysis (WGCNA) was performed to identify highly related resistance gene modules; in total, eight modules, including 2256 DEGs, were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of 2256 DEGs revealed that the genes significantly clustered into resistance-related pathways, such as the plant-pathogen interaction pathway, mitogen-activated protein kinases (MAPK) signaling pathway, and plant hormone signal transduction pathway. Among these pathways, we found that the flg22, Ca2+, hydrogen peroxide (H2O2), and abscisic acid (ABA) regulatory pathways were fully covered by 36 DEGs. Among the 36 DEGs, the gene Glyma.01G225100 (protein phosphatase 2C, PP2C) in the ABA regulatory pathway, the gene Glyma.16G031900 (WRKY transcription factor 22, WRKY22) in Ca2+ and H2O2 regulatory pathways, and the gene Glyma.04G175300 (calcium-dependent protein kinase, CDPK) in Ca2+ regulatory pathways were highly connected hub genes. These results indicate that the resistance of X149 to SC15 may depend on the positive regulation of flg22, Ca2+, H2O2, and ABA regulatory pathways. Our study further showed that superoxide dismutase (SOD) activity, H2O2 content, and catalase (CAT) and peroxidase (POD) activities were significantly up-regulated in the resistant line X149 compared with those in 0 hpi. This finding indicates that the H2O2 regulatory pathway might be dependent on flg22- and Ca2+-pathway-induced ROS generation. In addition, two hub genes, Glyma.07G190100 (encoding F-box protein) and Glyma.12G185400 (encoding calmodulin-like proteins, CMLs), were also identified and they could positively regulate X149 resistance. This study provides pathways for further investigation of SMV resistance mechanisms in soybean.

Bioactive Patch for Rotator Cuff Repairing via Enhancing Tendon-to-Bone Healing: A Large Animal Study and Short-Term Outcome of a Clinical Trial.

Tissue engineering has demonstrated its efficacy in promoting tissue regeneration, and extensive research has explored its application in rotator cuff (RC) tears. However, there remains a paucity of research translating from bench to clinic. A key challenge in RC repair is the healing of tendon-bone interface (TBI), for which bioactive materials suitable for interface repair are still lacking. The umbilical cord (UC), which serves as a vital repository of bioactive components in nature, is emerging as an important source of tissue engineering materials. A minimally manipulated approach is used to fabricate UC scaffolds that retain a wealth of bioactive components and cytokines. The scaffold demonstrates the ability to modulate the TBI healing microenvironment by facilitating cell proliferation, migration, suppressing inflammation, and inducing chondrogenic differentiation. This foundation sets the stage for in vivo validation and clinical translation. Following implantation of UC scaffolds in the canine model, comprehensive assessments, including MRI and histological analysis confirm their efficacy in inducing TBI reconstruction. Encouraging short-term clinical results further suggest the ability of UC scaffolds to effectively enhance RC repair. This investigation explores the mechanisms underlying the promotion of TBI repair by UC scaffolds, providing key insights for clinical application and translational research.