Shape-Persistent Conductive Nerve Guidance Conduits for Peripheral Nerve Regeneration.

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.

Outcome comparison of meniscal allograft transplantation (MAT) and meniscal scaffold implantation (MSI): a systematic review.

BACKGROUND: Although numerous studies have reported successful clinical outcomes of meniscal allograft transplantation (MAT) or meniscal scaffold implantation (MSI), the difference between the outcome of MAT and MSI remains unclear. PURPOSE: To compare the overall outcomes and survival rates of MAT and MSI, aiming to provide comprehensive evidence for determining the optimal treatment strategy for meniscal defects. METHODS: A systematic review was performed via a comprehensive search of PubMed, Embase, and the Cochrane Library. Studies of MAT or MSI were included according to the inclusion and exclusion criteria. The Lysholm score was chosen as the primary outcome measure, while secondary outcomes encompassed patient-reported outcome measures (PROMs), return to sports (RTS) rates, survival rates, and complication rates. The outcomes were stratified into two groups: MAT group and MSI group, followed by statistical comparison ( P <0.05). The quality of the included studies was assessed by the Cochrane Risk of Bias 2 (RoB2) assessment tool for randomized controlled trials (RCTs) and the Coleman Methodology Score (CMS) for non-randomized controlled trials. RESULTS: A total of 3932 patients (2859 MAT, 1073 MSI) in 83 studies (51 MAT, 32 MSI) had the overall significant improvement in all clinical scores. The group MSI had a higher Lysholm score of both preoperative ( P =0.002) and postoperative ( P <0.001) than group MAT; however, the mean improvements were similar between the two groups ( P =0.105). Additionally, MSI had higher improvements of IKDC ( P <0.001), KOOS symptom ( P =0.010), KOOS pain ( P =0.036), and KOOS ADL ( P =0.004) than MAT. Interestingly, MAT had higher preoperative ( P =0.018) and less postoperative VAS pain ( P =0.006), which was more improved in MAT ( P <0.001). Compared with MAT, MSI had a higher 10-year survival rate ( P =0.034), a similar mid-term survival rate MAT ( P =0.964), and a lower complication rate ( P <0.001). CONCLUSION: Both MAT and MSI could have good clinical outcomes after surgery with a similar improvement in Lysholm score. MSI had a higher 10-year survival rate and fewer complications than MAT. LEVEL OF EVIDENCE: Level IV, systematic review.

Ambient air pollution exposure and the risk of probable sarcopenia: A prospective cohort study.

BACKGROUND: Sarcopenia is characterized by decreased muscle mass and strength, posing threat to quality of life. Air pollutants are increasingly recognized as risk factors for diseases, while the relationship between the two remains to be elucidated. This study investigated whether exposure to ambient air pollution contributes to the development of sarcopenia. METHODS: We employed the data from the UK Biobank with 303,031 eligible participants. Concentrations of PM2·5, NO2, and NOx were estimated. Cox proportional hazard regression models were applied to investigate the associations between pollutants and sarcopenia. RESULTS: 30,766 probable sarcopenia cases was identified during the follow-up. We observed that exposure to PM2.5 (HR, 1.232; 95% CI, 1.053-1.440), NO2 (HR, 1.055; 95% CI, 1.032-1.078) and NOx (HR, 1.016; 95% CI, 1.007-1.026) were all significantly associated with increased risk for probable sarcopenia for each 10 µg/m3 increase in pollutant concentration. In comparison with individuals in the lowest quartiles of exposure, those in the upper quartiles had significantly increased risk of probable sarcopenia. Sarcopenia-related factors, e.g., reduced lean muscle mass, diminished walking pace, and elevated muscle fat infiltration ratio, also exhibited positive associations with exposure to ambient air pollution. On the contrary, high level physical activity significantly mitigated the influence of air pollutants on the development of probable sarcopenia. CONCLUSIONS: Air pollution exposure elevated the risk of developing sarcopenia and related manifestations in a dose-dependent manner, while physical activity maintained protective under this circumstance. Efforts should be made to control air pollution and emphasize the importance of physical activity for skeletal muscle health under this circumstance.

Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting.

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% of the general population and more than 20% of patients with diabetes mellitus. Pathologically, joint capsule fibrosis resulting from fibroblast activation is the key event. The activated fibroblasts are proliferative and contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, are still lacking. In this study, microRNA-122 was first identified from sequencing data as a potential therapeutic agent to antagonize fibroblast activation. Then, Agomir-122, an analog of microRNA-122, was loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), a carrier with excellent biocompatibility for the agent delivery. Moreover, relying on the homologous targeting effect, we coated Agomir-122@NP with the cell membrane derived from activated fibroblasts (Agomir-122@MNP), with an attempt to inhibit the proliferation, contraction, and collagen production of abnormally activated fibroblasts. After confirming the targeting effect of Agomir-122@MNP on activated fibroblasts in vitro, we proved that Agomir-122@MNP effectively curtailed fibroblasts activation, ameliorated joint capsule fibrosis, and restored range of motion in mouse models both prophylactically and therapeutically. Overall, an effective targeted delivery method was developed with promising translational value against frozen shoulder.

Early Weight-bearing Rehabilitation Protocol After Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament (ACL) injury is one of the common sports injuries. Anterior cruciate ligament reconstruction (ACLR) is the mainstream treatment for ACL injury, aiming to regain normal anatomical structure and stability of the knee joint and promote the patient's return to sports. Under the guidance of the concept of enhanced recovery after surgery, early weight-bearing rehabilitation (EWB) is an important factor affecting patient function and quality of life. However, there is no consensus on whether EWB rehabilitation can be performed after ACL surgery. This study aims to explore the safety and feasibility of EWB after ACL surgery. The study implemented a gradual EWB rehabilitation program in the experimental group, including weight-shifting training, balance training, and gait training on the affected lower limb, and assessed wound healing and stability of the knee joint. The study found that EWB after ACLR is safe and feasible. EWB rehabilitation not only does not pose a negative effect on the patient's knee pain, swelling, wound healing, and stability, but also helps to improve knee active flexion and quality of life faster and better. The EWB program in this study is simple, safe, and effective, and it provides strong theoretical guidance and practical demonstration for accelerated rehabilitation after ACLR.

Macrophage-Myofibroblast Transition as a Potential Origin for Skeletal Muscle Fibrosis After Injury via Complement System Activation.

Background: Acute skeletal muscle injury is common in sports. The injured muscle cannot fully recover due to fibrosis resulting from myofibroblasts. Understanding the origin of fibroblasts is, therefore, important for the development of anti-fibrotic therapies. Accumulating evidence shows that a mechanism called macrophage-myofibroblast transition (MMT) can lead to tissue or organ fibrosis, yet it is still unclear whether MMT exists in skeletal muscle and the exact mechanisms. Methods: Single-cell transcriptome of mice skeletal muscle after acute injury was analyzed with a specific attention on the process of MMT. Cell-cell interaction network, pseudotime trajectory analysis, Gene Ontology (GO), and Kyoto Genome Encyclopedia (KEGG) were conducted. A series of experiments in vivo and in vitro were launched for verification. Results: Single cell transcriptomic analysis indicated that, following acute injury, there were much interactions between macrophages and myofibroblasts. A detailed analysis on macrophages indicated that, CD68+α-SMA+ cells, which represented the status of MMT, mainly appeared at five days post-injury. KEGG/GO analysis underlined the involvement of complement system, within which C3ar1, C1qa, C1qb, and C1qc were up-regulated. Trajectory analysis also confirmed a potential shift from macrophages to myofibroblasts. These findings were verified by histological study in mice skeletal muscle, that there were much MMT cells at five days, declined gradually, and vanished 14 days after trauma, when there was remarkable fibrosis formation within the injured muscle. Moreover, C3a stimulation could directly induce MMT in BMDMs. Conclusion: Fibrosis following acute injury is disastrous to skeletal muscle, but the origin of myofibroblasts remains unclear. We proved that, following acute injury, macrophage-myofibroblast transition happened in skeletal muscle, which may contribute to fibrosis formation. This phenomenon mainly occurred at five days post-injury. The complement system can activate MMT. More evidence is needed to directly support the pro-fibrotic role of MMT in skeletal muscle fibrosis after acute injury.