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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Levels of Evidence 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.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.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°.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.Level II. [ABSTRACT FROM AUTHOR]

Systematic characterization of biological effects to genetic perturbation is essential to the application of molecular biology and biomedicine. However, the experimental exhaustion of genetic perturbations on the genome-wide scale is challenging. Here, we show TranscriptionNet, a deep learning model that integrates multiple biological networks to systematically predict transcriptional profiles to three types of genetic perturbations based on transcriptional profiles induced by genetic perturbations in the L1000 project: RNA interference, clustered regularly interspaced short palindromic repeat, and overexpression. TranscriptionNet performs better than existing approaches in predicting inducible gene expression changes for all three types of genetic perturbations. TranscriptionNet can predict transcriptional profiles for all genes in existing biological networks and increases perturbational gene expression changes for each type of genetic perturbation from a few thousand to 26 945 genes. TranscriptionNet demonstrates strong generalization ability when comparing predicted and true gene expression changes on different external tasks. Overall, TranscriptionNet can systemically predict transcriptional consequences induced by perturbing genes on a genome-wide scale and thus holds promise to systemically detect gene function and enhance drug development and target discovery., (© The Author(s) 2024. Published by Oxford University Press.)

Exosomes, a specialised type of extracellular vesicle, have attracted significant attention in the realm of tendon/ligament repair as a potential biologic therapeutic tool. While the competence of key substances responsible for the delivery function was gradually elucidated, series of shortcomings exemplified by the limited stability still need to be improved. Therefore, how to take maximum advantage of the biological characteristics of exosomes is of great importance. Recently, the comprehensive exploration and application of biomedical engineering has improved the availability of exosomes and revealed the future direction of exosomes combined with biomaterials. This review delves into the present application of biomaterials such as nanomaterials, hydrogels, and electrospun scaffolds, serving as the carriers of exosomes in tendon/ligament repair. By pinpointing and exploring their strengths and limitations, it offers valuable insights, paving the way the future direction of biomaterials in the application of exosomes in tendon/ligament repair in this field., Competing Interests: Conflicts of interest statement: The authors declare no competing interests.