3D-bioprinted adipose-derived stem cell-secreted GAS6 + -sEVs reprogram microglia polarization and alleviate neuroinflammation in traumatic brain injury.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Traumatic brain injury (TBI)-induced neuroinflammation, driven by inflammatory microglial polarization, continues to pose a significant regenerative and clinical challenge. Small extracellular vesicles (sEVs) have demonstrated great potential in mitigating post-TBI inflammation. Nevertheless, the limited yield and efficacy of sEVs produced via conventional two-dimensional (2D) culture systems (2D-sEVs) substantially hinder their clinical applicability. Moreover, effective strategies for the therapeutic application of sEVs in TBI treatment, along with an understanding of their underlying mechanisms, remain largely unexplored. In this study, we employed a 3D coaxial bioprinting method to encapsulate adipose-derived stem cells (ADSCs) within a hydrogel microfiber, facilitating 3D culturing and large-scale production of 3D-sEVs. Additionally, we utilized GelMA hydrogel for the sustained release of 3D-sEVs and evaluated their effects in LPS-activated microglia as well as in a TBI mouse model. Our results demonstrated that 3D culture significantly enhanced sEV production. GelMA improved sEV stability and prolonged sEV release up to 30 days in vivo. Compared to 2D-sEVs, 3D-sEVs offered superior therapeutic benefits. Specifically, 3D-sEVs substantially reduced neuroinflammation and brain tissue loss while accelerating motor function recovery in TBI mice. Furthermore, 3D-sEVs shifted pr

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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