Three-Dimensional-Printed Gelatin Methacryloyl Scaffold Loaded with Extracellular Vesicles Derived from H2S Preconditioned Mesenchymal Stromal Cells Promotes Neuronal Regeneration in Rats with Spinal Cord Injury.

BACKGROUND

spinal cord injury (SCI) causes irreversible motor and sensory deficits with limited effective treatments. Mesenchymal stromal cells (MSCs) exert therapeutic effects largely through extracellular vesicles (EVs). Preconditioning MSCs with a hydrogen sulfide (H2S) donor enhance the therapeutic potential of EVs.

OBJECTIVE

this study is aimed to develop a 3D-printed gelatin methacryloyl (GelMA) scaffold loaded with H2S-preconditioned MSC-derived EVs (H2S-EVs) to promote motor function recovery in SCI.

METHODS

H2S-EVs were isolated from NaHS (an H2S donor)-preconditioned MSCs and incorporated into a 3D-printed GelMA scaffold (3D/GelMA/EVs). Scaffold mechanical properties and H2S-EVs. The scaffold's therapeutic efficacy was evaluated in a rat SCI model.

RESULTS

MiRNA microarray revealed miR-7a-5p as the most upregulated miRNA in H2S-EVs. The 3D/GelMA/EVs scaffold exhibited an appropriate elastic modulus and porous structure, enabling sustained local EVs release. In vivo, the scaffold significantly improved motor function recovery in SCI rats.

CONCLUSION

these results indicated that H2S-EVs provided an important therapeutic tool against SCI by miR-7a-5p and 3D/GelMA/EVs scaffolds were ideal biomaterials for the intervention of SCI.