ArticleMaterials today. Bio2026
Enhancing the regenerative potential of MSC-derived exosomes via 3D microenvironment modulation for cartilage repair.
Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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7 authors.
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Abstract
Articular cartilage defects remain a major clinical challenge due to their poor self-repair capacity. Mesenchymal stem cell (MSC)-derived exosomes have emerged as promising cell-free therapeutics; however, conventional two-dimensional (2D) cultures yield exosomes with limited bioactivity. Here, we engineered hierarchical macro-microporous scaffolds using gelatin methacryloyl (GelMA) hydrogel and cartilage extracellular matrix (ECM) to establish biomimetic three-dimensional (3D) microenvironments for MSC culture. This approach yielded three distinct exosome types-2D-Exo, GelMA-derived exosomes (G-Exo), and ECM-derived exosomes (E-Exo). Compared with 2D-Exo, 3D-derived exosomes significantly enhanced MSC proliferation, migration, chondrogenic differentiation, immunomodulation, and chondrocyte protection under inflammatory conditions, with E-Exo exhibiting the most potent effects. In vivo, E-Exo combined with a decellularized cartilage ECM (DCM) scaffold promoted robust hyaline cartilage regeneration in a rat model. Mechanistically, we identify a key pathway by which E-Exo drives chondrogenesis: they are enriched in miR-503-5p, which suppresses Smad7 to enhance TGF-β/Smad2/3 signaling. These findings highlight ECM-based 3D culture as an effective strategy to optimize exosome bioactivity and provide a clinically translatable approach for cell-free cartilage regeneration.
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