Porous Photocrosslinkable Hydrogel Functionalized with USC Derived Small Extracellular Vesicles for Corpus Spongiosum Repair

Reconstruction of a full-thickness spongy urethra is difficult because a corpus spongiosum (CS) defect cannot be repaired using self-healing or substitution urethroplasty. Small extracellular vesicles (sEVs) secreted by urine-derived stem cells (USC-sEVs) strongly promote vascular regeneration. In this study, it is aimed to explore whether USC-sEVs promote the repair of CS defects. To prolong the in vivo effects of USC-sEVs, a void-forming photoinduced imine crosslinking hydrogel (vHG) is prepared and mixed with the USC-sEV suspension. vHG encapsulated with USC-sEVs (vHG-sEVs) is used to repair a CS defect with length of 1.5 cm and width of 0.8 cm. The results show that vHG-sEVs promote the regeneration and repair of CS defects. Histological analysis reveals abundant sinusoid-like vascular structures in the vHG-sEV group. Photoacoustic microscopy indicates that blood flow and microvascular structure of the defect area in the vHG-sEV group are similar to those in the normal CS group. This study confirms that the in situ-formed vHG-sEV patch appears to be a valid and promising strategy for repairing CS defects.