Osteoarthritis (OA) is characterized by progressive cartilage degeneration with increasing prevalence and unsatisfactory treatment efficacy. Exosomes derived from mesenchymal stem cells play an important role in alleviating OA by promoting cartilage regeneration, inhibiting synovial inflammation and mediating subchondral bone remodeling without the risk of immune rejection and tumorigenesis. However, low yield, weak activity, inefficient targeting ability and unpredictable side effects of natural exosomes have limited their clinical application. At present, various approaches have been applied in exosome engineering to regulate their production and function, such as pretreatment of parental cells, drug loading, genetic engineering and surface modification. Biomaterials have also been proved to facilitate efficient delivery of exosomes and enhance treatment effectiveness. Here, we summarize the current understanding of the biogenesis, isolation and characterization of natural exosomes, and focus on the large-scale production and preparation of engineered exosomes, as well as their therapeutic potential in OA, thus providing novel insights into exploring advanced MSC-derived exosome-based cell-free therapy for the treatment of OA.

Background: Medial meniscal posterior root tear (MMPRTs) is a common lesion of the knee joint, and repair surgery is a well-established treatment option. However, patients with obvious varus alignment are at an increased risk for MMPRT and can suffer from a greater degree of medial meniscus extrusion, which leads to the development of osteoarthritis following repair. The efficacy of high tibial osteotomy (HTO) as a means of correcting this malformation, and its potential benefits for MMPRT repair, remains unclear. Purpose: To explore whether HTO influenced the outcome of MMPRT repair in clinical scores and radiological findings. Study design: Systematic review. Methods: According to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines, we searched PubMed, Embase, Web of Science, and the Cochrane Library databases for studies reporting the outcomes of MMPRT repair and extracted data about characteristics of patients, clinical functional scores and radiologic outcomes. One reviewer extracted the data and 2 reviewers assessed the risk of bias and performed a synthesis of the evidence. Articles were eligible if they reported the results of MMPRT repair with exact mechanical axis (registered in the International Prospective Register of Systematic Reviews, CRD42021292057). Results: Fifteen studies with 625 cases of high methodological quality were identified. Eleven studies were assigned to the MMPRT repair group (M) with 478 cases performing MMPRT repair only, and others belonged to the MMPRT repair and HTO group (M and T) performing HTO and MMPRT repair. Most of the studies had significantly improved clinical outcome scores, especially in M groups. And the radiologic outcomes showed that the osteoarthritis deteriorated in both groups with similar degree in about 2-year follow-up. Conclusion: HTO is a useful supplement in treating MMPRT patients with severe osteoarthritis and the clinical and radiological outcomes were similar with MMPRT repair alone. Which would be better for patients’ prognosis generally, performing MMPRT repair alone or a combination of HTO and MMPRT repair, was still controversial. We suggested taking K-L grade into account. Large-scale randomized control studies were called for in the future to help make better clinical decisions. Level of evidence: III

Background: Anterior cruciate ligament (ACL) reconstruction has been the gold standard for primary ACL rupture since the 1990s. In the past decade, ACL repair has received renewed attention and increased research. Purpose: To compare the clinical outcomes of modern augmented ACL repair versus autograft reconstruction for ACL ruptures. Study Design: Systematic review; Level of evidence, 3. Methods: A search of the PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases was conducted for prospective or retrospective comparative studies published between January 1, 2010, and January 3, 2023, with a minimum 2-year follow-up. Two independent reviewers performed data extraction and methodological quality assessment. Sensitivity analysis was performed to maintain the stability of results. Results: Nine studies were included (minimum follow-up period, 24-60 months). The total sample size was 833 patients (augmented repair group: 358 patients; autograft ACL reconstruction group: 475 patients). There were 4 randomized controlled trials (level 1), 1 prospective comparative study (level 2), 2 retrospective comparative studies (level 3), and 2 case-control studies (level 3). The augmented ACL repair group attained significantly higher Lysholm score (weighted mean difference [WMD] = 1.57; 95% confidence interval [CI], 0.14-3.01; P = .03) and hamstring strength (WMD = 36.69; 95% CI, 29.07-44.31; P < .01) but had higher rates of hardware removal (odds ratio [OR] = 6.30; 95% CI, 2.44-16.23; P = .0001), reoperation (OR = 1.87; 95% CI, 1.33-2.62; P = .0003), and failure (OR = 1.58; 95% CI, 1.03-2.43; P = .0003) compared with the autograft ACL reconstruction group. No significant differences were observed between the repair and reconstruction groups regarding postoperative International Knee Documentation Committee scores, Tegner scores, knee laxity, satisfaction, ACL revisions, complications, and reoperation rather than revision. Conclusion: Augmented ACL repair was associated with higher rates of reoperation, hardware removal, and failure compared with autograft ACL reconstruction in studies with minimum 2-year follow-up data. However, augmented ACL repair had higher Lysholm scores and hamstring strength versus autograft ACL reconstruction.