Background Osteoarthritis (OA) is the most prevalent joint disease, and to date, no options for effective tissue repair and restoration are available. With the aim of developing new therapies, the impact of mesenchymal stem cells (MSCs) has been explored, and the efficacy of MSCs started to be deciphered. A strong paracrine capacity relying on both secreted and vesicle-embedded (EVs) protein or nucleic acid-based factors has been proposed as the principal mechanism that contributes to tissue repair. This work investigated the mechanism of internalization of extracellular vesicles (EVs) released by adipose-derived MSCs (ASCs) and the role of shuttled miRNAs in the restoration of homeostasis in an in vitro model of human fibroblast-like synoviocytes (FLSs) from OA patients. Methods ASC-EVs were isolated by differential centrifugation and validated by flow cytometry and nanoparticle tracking analysis. ASC-EVs with increased hyaluronan (HA) receptor CD44 levels were obtained culturing ASCs on HA-coated plastic surfaces. OA FLSs with intact or digested HA matrix were co-cultured with fluorescent ASC-EVs, and incorporation scored by flow cytometry and ELISA. ASC-EV complete miRNome was deciphered by high-throughput screening. In inflamed OA FLSs, genes and pathways potentially regulated by ASC-EV miRNA were predicted by bioinformatics. OA FLSs stimulated with IL-1β at physiological levels (25 pg/mL) were treated with ASC-EVs, and expression of inflammation and OA-related genes was measured by qRT-PCR over a 10-day time frame with modulated candidates verified by ELISA. Results The data showed that HA is involved in ASC-EV internalization in FLSs. Indeed, both removal of HA matrix presence on FLSs and modulation of CD44 levels on EVs affected their recruitment. Bioinformatics analysis of EV-embedded miRNAs showed their ability to potentially regulate the main pathways strictly associated with synovial inflammation in OA. In this frame, ASC-EVs reduced the expression of pro-inflammatory cytokines and chemokines in a chronic model of FLS inflammation. Conclusions Given their ability to affect FLS behavior in a model of chronic inflammation through direct interaction with HA matrix and miRNA release, ASC-EVs confirm their role as a novel therapeutic option for osteoarthritic joints. Electronic supplementary material The online version of this article (10.1186/s13287-019-1215-z) contains supplementary material, which is available to authorized users.

The Delta III prosthesis restores shoulder function but has biomechanical limits. Its use should be limited to elderly patients with severe impairment of the glenohumeral joint. Scapular notching is a main concern for the long-term survival of the implant.

Background: This study aims to investigate the clinical and radiological efficacy of three-dimensional acellular scaffolds (MaioRegen) in restoring osteochondral knee defects. Methods: MEDLINE, Scopus, CINAHL, Embase, and Cochrane Databases were searched for articles in which patients were treated with MaioRegen for osteochondral knee defects. Results: A total of 471 patients were included in the study (mean age 34.07 ± 5.28 years). The treatment involved 500 lesions divided as follows: 202 (40.4%) medial femoral condyles, 107 (21.4%) lateral femoral condyles, 28 (5.6%) tibial plateaus, 46 (9.2%) trochleas, 74 (14.8%) patellas, and 43 (8.6%) unspecified femoral condyles. Mean lesion size was 3.6 ± 0.85 cm2. Only four studies reported a follow-up longer than 24 months. Significant clinical improvement has been reported in almost all studies with further improvement up to 5 years after surgery. A total of 59 complications were reported of which 52 (11.1%) experienced minor complications and 7 (1.48%) major complications. A total of 16 (3.39%) failures were reported. Conclusion: This systematic review describes the current available evidence for the treatment of osteochondral knee defects with MaioRegen Osteochondral substitute reporting promising satisfactory and reliable results at mid-term follow-up. A low rate of complications and failure was reported, confirming the safety of this scaffold. Considering the low level of evidence of the study included in the review, this data does not support the superiority of the Maioregen in terms of clinical improvement at follow-up compared to conservative treatment or other cartilage techniques.

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