Hydrogels Loaded with Mesenchymal Stem Cells Extracellular Vesicles for Treating Knee Joint Disorders: A Systematic Review

• Published in: Regenerative engineering and translational medicine Vol. 10; no. 2; pp. 189 - 204
• Main Authors: Garcia-Motta, Homero, Bonifacio, Mirian, Martignago, Cintia Cristina Santi, Souza-Silva, Lais Caroline, Soares-Silva, Beatriz, Parisi, Julia Risso, Assis, Lívia, Ribeiro, Daniel Araki, Ribeiro, Alessandra Mussi, Rennó, Ana Cláudia
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2024
• Subjects: Biomaterials; Biomedical Engineering and Bioengineering; Chemistry and Materials Science; Materials Science; Regenerative Medicine/Tissue Engineering; Review; Osteochondral Defect; Exosomes; Osteoarthritis; Nanovesicles
• ISSN: 2364-4133; 2364-4141
• DOI: 10.1007/s40883-023-00326-w

Purpose Knee joints are prone to injuries and degenerative diseases; however, current treatments have limited effectiveness in cartilage regeneration. Extracellular vesicles (EVs) derived from MSCs offer potential for promoting cartilage regeneration, especially when associated with hydrogel for controllable delivery. In this context, the systematic review aims to assess the therapeutic potential of hydrogel-loaded EVs in animal models of knee joint disorders. Material and Methods This review was conducted from March to June 2023, adhering to the Priority Reporting Items Guidelines for Systematic Reviews and Meta-Analysis (PRISMA) and the SYRCLE Prejudice Risk Tool for Quality Assessment. The selected databases included Embase, Cochrane, Web of Science, PubMed, and Lilacs. Results The survey resulted in 344 articles suitable for sorting. After applying pre-defined criteria, 8 studies were selected for inclusion, where the heterogeneity of materials and the absence of standardized protocols for manufacturing EVs-enriched hydrogels are apparent. In the groups treated with EVs-enriched hydrogel, improvements were observed in terms of morphology, with a more organized and smoother structure, as well as an increased number of chondrocytes and more significant deposition of GAG in the treated animals. Furthermore, there was a greater enhancement in immunostaining for COL II, ACAN, and SOX-9, while matrix-degrading factors exhibited a reduction. Conclusion Hydrogels loaded with EVs show promise for stimulating cartilage repair and enhancing cell proliferation. The combination of hydrogels and EVs could represent an innovative therapeutic intervention for cartilage repair injuries. Lay Summary This systematic review assessed studies on hydrogel-loaded EVs for cartilage repair. Out of 344 articles, 8 were included, highlighting material heterogeneity and a lack of standardized protocols. EVs-enriched hydrogel treatments showed improved morphology, increased chondrocytes, and enhanced GAG deposition. Notably, immunostaining for key markers exhibited enhancement, while matrix-degrading factors decreased. These findings suggest that hydrogels loaded with EVs hold potential for stimulating cartilage repair and promoting cell proliferation. Combining hydrogels with EVs may offer an innovative therapeutic approach for cartilage repair injuries.