Osteoarthritis (OA) is a degenerative disease that lacks regenerative treatment options. Current research focuses on mesenchymal stem cells (MSCs) and Platelet-Rich Plasma (PRP) as regenerative therapies, but extracellular vesicles (EVs) have shown to be more advantageous. This study compares the regenerative potential of human umbilical cord MSC-derived EVs (cEVs) and platelet-derived EVs (pEVs) in ex vivo and in vivo OA models.

In the ex vivo study, OA conditions were induced in human cartilage explants, which were then treated either with pEVs or cEVs. Results showed a higher content of DNA and collagen in the pEVs group compared to control and cEVs groups, suggesting that pEVs could be a potential alternative to cEVs.

In the in vivo study, an OA model was established in the knee joints of rats through MIA (monoiodoacetate) injection and then treated either with pEVs or cEVs. Results showed that pEVs-treated knee joints had better subchondral bone integrity and greater OA reversion, particularly in female rats, indicating that pEVs are a viable regeneration treatment for OA and outperform cEVs in terms of efficacy.

Overall, the study demonstrates the potential of EVs as a regenerative treatment for OA, with pEVs showing promising results in both ex vivo and in vivo models. The use of pEVs in clinical practice could provide a faster path to translation due to the established use of platelet concentrates in therapeutics. However, further studies are needed to fully evaluate the potential of pEVs for OA treatment and to elucidate the mechanisms behind their regenerative effects.

Acknowledgments: The authors thank Dr Fernando Hierro (UIB) for their technical contribution with TEM, Mª Trinidad García (UIB) for the access to radioactivity facilities, Aina Arbós (IUNICS) for her contribution in the histology staining, María Tortosa (IdISBa) for her assistance with the animal care and ADEMA School of Dentistry for the access to the cone beam computed tomography (CBCT).

Funding: This research was funded by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, co-funded by the ESF European Social Fund and the ERDF European Regional Development Fund (MS16/00124; CP16/00124), PROGRAMA JUNIOR del proyecto TALENT PLUS, construyendo SALUD, generando VALOR (JUNIOR01/18), financed by the sustainable tourism tax of the Balearic Islands; the Direcció General d'Investigació and Conselleria d'Investigació, Govern Balear (FPI/2046/2017); the Mecanisme de Recuperació i Resiliència, intended to execute research projects of «Noves polítiques públiques per a un mercat de treball dinàmic, resilient i inclusiu», collected in Pla de Recuperació, Transformació i Resiliència, financed by European Union-Next Generation EU and driven by SOIB and Conselleria de Fons Europeus, Universitat i Cultura i la Conselleria de Model Econòmic, Turisme i Treball (NG0421) and the grant SYN20/03 from IdISBa.

Introduction: In this work a bioactive glass-ceramic (GC) in the system SiO2-CaO-P2O5 was evaluated as bone substitute biomaterial. In this sense, the capacity of mesenchymal stem cells (MSCs) to adhere, proliferate and differentiate into osteoblast (OBs) with or without GC was investigated. Two types of culture medium, i.e. growth medium (GM) and osteogenic medium (OM), were evaluated.

Materials and Methods: The GC was obtained by heat treatment of a bioactive glass obtained by the sol-gel method. Isolation and culture of MSCs: The adult MSCs were isolated from bone marrow of adult rabbits obtained by direct aspirations of ileac crest. Isolation and culture of OBs: The OBs used as control were obtained by enzymatic digestion. Behavior of MSCs on GC: For the study of the behavior of isolated MSCs on the GC, two series of 96-well plates were seeded, one plate with GM and the other one with OM. The number of cells was evaluated through the XTT assay. OC production and CD90 expression of cells cultured in both media were measured to evaluate the differentiation of MSCs into OBs. Statistical analysis: A variance analysis (ANOVA) was carried out.

Results: The number of cells growing in OM and GM, there were no significant differences between them. The MSCs under the conditions of this study expressed an osteoblastic phenotype (OC production, decrease CD90 expression, mineralized extracell matrix). These two effects took place by either the action of exposing the MSCs to a MO and by the effect of the GC.