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

Abstract 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.