Background: Cartilage repair still presents a challenge to clinicians and researchers alike. A more effective, simpler procedure that can produce hyaline-like cartilage is needed for articular cartilage repair. Hypothesis: A technique combining microfracture with a biomaterial scaffold of perforated decalcified cortical-cancellous bone matrix (DCCBM; composed of cortical and cancellous parts) would create a 1-step procedure for hyaline-like cartilage repair. Study Design: Controlled laboratory study. Methods: For the in vitro portion of this study, mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of New Zealand White rabbits. Scanning electron microscopy (SEM), confocal microscopy, and 1,9-dimethylmethylene blue assay were used to assess the attachment, proliferation, and cartilage matrix production of MSCs grown on a DCCBM scaffold. For the in vivo experiment, full-thickness defects were produced in the articular cartilage of the trochlear groove of 45 New Zealand White rabbits, and the rabbits were then assigned to 1 of 3 treatment groups: perforated DCCBM combined with microfracture (DCCBM+M group), perforated DCCBM alone (DCCBM group), and microfracture alone (M group). Five rabbits in each group were sacrificed at 6, 12, or 24 weeks after the operation, and the repair tissues were analyzed by histological examination, assessment of matrix staining, SEM, and nanoindentation of biomechanical properties. Results: The DCCBM+M group showed hyaline-like articular cartilage repair, and the repair tissues appeared to have better matrix staining and revealed biomechanical properties close to those of the normal cartilage. Compared with the DCCBM+M group, there was unsatisfactory repair tissues with less matrix staining in the DCCBM group and no matrix staining in the M group, as well as poor integration with normal cartilage and poor biomechanical properties. Conclusion: The DCCBM scaffold is suitable for MSC growth and hyaline-like cartilage repair induction when combined with microfracture. Clinical Relevance: Microfracture combined with a DCCBM scaffold is a promising method that can be performed and adopted into clinical treatment for articular cartilage injuries.
Exosomes have been proven to play a positive role in tendon and tendon–bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon–bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a “snowball” search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon–bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon–bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon–bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials.
Osteoarthritis (OA) is a common degenerative disease. Although some biomarkers and drug targets of OA have been discovered and employed, limitations and challenges still exist in the targeted therapy of OA. Mendelian randomization (MR) analysis has been regarded as a reliable analytic method to identify effective therapeutic targets. Thus, we aimed to identify novel therapeutic targets for OA and investigate their potential side effects based on MR analysis. In this study, two-sample MR, colocalization analysis, summary-data-based Mendelian randomization (SMR) and Mendelian randomization phenome-wide association study (MR-PheWAS) were conducted. We firstly analyzed data from 4907 plasma proteins to identify potential therapeutic targets associated with OA. In addition, blood expression quantitative trait loci (eQTLs) data sources were used to perform additional validation. A protein–protein interaction (PPI) network was also constructed to delve into the interactions among identified proteins. Then, MR-PheWASs were utilized to assess the potential side effects of core therapeutic targets. After MR analysis and FDR correction, we identified twelve proteins as potential therapeutic targets for knee OA or hip OA. Colocalization analysis and additional validation supported our findings, and PPI networks revealed the interactions among identified proteins. Finally, we identified MAPK3 (OR = 0.855, 95% CI: 0.791–0.923, p = 6.88 × 10−5) and GZMK (OR = 1.278, 95% CI: 1.131–1.444, p = 8.58 × 10−5) as the core therapeutic targets for knee OA, and ITIH1 (OR = 0.847, 95% CI: 0.784–0.915, p = 2.44 × 10−5) for hip OA. A further MR phenome-wide association study revealed the potential side effects of treatments targeting MAPK3, GZMK, and ITIH1. This comprehensive study indicates twelve plasma proteins with potential roles in knee and hip OA as therapeutic targets. This advancement holds promise for the progression of OA drug development, and paves the way for more efficacious treatments of OA.
1 March 2022 in Orthopaedic Journal of Sports Medicine
Background: Some studies have advocated the use of suture button fixation during Bristow-Latarjet surgery to reduce complications associated with screw fixation. However, data comparing these fixation methods are relatively incomplete. Purpose: To investigate the efficacy of modified arthroscopic Bristow-Latarjet surgery and compare the clinical and radiographic outcomes using screw versus suture button fixation. Study Design: Cohort study; Level of evidence, 3. Methods: We evaluated 136 patients with traumatic anterior shoulder instability who underwent the modified arthroscopic Bristow-Latarjet surgery between June 2015 and February 2018. Of these patients, 117 who met the inclusion criteria were enrolled at a mean follow-up of 3.3 ± 0.7 years. Shoulders were separated into 2 groups based on fixation technique: screw fixation (group A; n = 63) or suture button fixation (group B; n = 54). Computed tomography imaging findings and clinical results were assessed preoperatively; immediately after operation; and postoperatively at 3 months, 6 months, 1 year, and final follow-up. Results: There were no significant differences between the groups in terms of postoperative clinical scores, the level of return to sports, range of motion, graft position, or reoperation rates. Bone healing was observed in 97.4% of the cases overall (114/117), with 98.4% bone union in group A and 96.3% in group B at final follow-up. Bone absorption was more common in group A (n = 30; 47.6%) compared with group B (n = 10; 18.5%) ( P = .003). There were no hardware-related complications in group B, compared with 7.9% of patients in group A ( P = .034). One patient in group B had a recurrent dislocation due to an unexpected event, and there were no recurrent dislocations in group A. Conclusion: After the modified arthroscopic Bristow-Latarjet procedure, both suture button and screw fixation methods demonstrated high bony healing rates and low risk of recurrence. Less coracoid graft resorption and no hardware-related complications were seen with suture button fixation.