High-yield BMSC-derived exosomes by the 3D culture system to enhance the skin wound repair

Wound defects pose a substantial challenge in clinical practice, often resulting in prolonged healing times and an elevated risk of infection. Insufficient vascularization is a critical factor that adversely affects wound healing. Exosomes obtained from bone mesenchymal stem cells (BMSC-exos) have demonstrated significant promise in accelerating tissue repair by promoting angiogenesis. However, their limited yield and suboptimal biological functions impede widespread clinical application in enhancing wound healing. Prior research has indicated that 3D cultures can boost exosome secretion when compared to conventional 2D cultures. However, the currently prevalent 3D culture methods often necessitate expensive equipment or cumbersome procedures. This study investigates a cost-effective and user-friendly 3D culture system developed using gelatin methacrylate (GelMA). Our findings indicate that a 5% concentration of GelMA provides an optimal environment for the 3D culture of BMSCs. Furthermore, we observed that 3D culture significantly delays the senescence of BMSCs, thereby creating favorable conditions for the sustained production of exosomes. Additionally, 3D cultivation has the potential to boost exosome secretion and enhance their angiogenic capabilities. <i>In vivo</i> experiments further confirmed that BMSC-exos from a 3D environment exhibit enhanced capabilities to promote wound healing. These results suggest that GelMA-based 3D cultures offer a novel strategy for both industrial production and clinical application of exosomes.